Robotic Versus Laparoscopic Hepatectomy: A Single Surgeon Experience of 629 Consecutive Minimally Invasive Liver Resections.

BACKGROUND: Robotic surgery has the potential to broaden the indications for minimally invasive liver surgery owing to its technical advantages. This paper compares our experience with robotic liver surgery (RLS) with conventional laparoscopic liver surgery (LLS). METHODS: All consecutive liver resections between October 2011 and October 2022 were selected from our prospective database to be included in this cohort study. Patients who underwent RLS were compared with a LLS group for operative and postoperative outcomes. RESULTS: In total, 629 patients were selected from our database, including 177 patients who underwent a RLS and 452 patients who had LLS. Colorectal liver metastasis was the main indication for surgery in both groups. With the introduction of RLS, the percentage of open resections decreased significantly (32.6% from 2011 to 2020 vs. 11.5% from 2020 onward, P < 0.001). In the robotic group, redo liver surgery was more frequent (24.3% vs. 16.8%, P = 0.031) and the Southampton difficulty score was higher (4 [IQR 4 to 7] vs. 4 [IQR 3 to 6], P = 0.02). Median blood loss was lower (30 vs. 100 ml, P < 0.001), and postoperative length of stay (LOS) was shorter in the robotic group (median 3 vs. 4 days, P < 0.001). There was no significant difference in postoperative complications. Cost related to the used instruments and LOS was significantly lower in the RLS group (median €1483 vs. €1796, P < 0.001 and €1218 vs. €1624, P < 0.001, respectively), while cost related to operative time was higher (median €2755 vs. €2470, P < 0.001). CONCLUSIONS: RLS may allow for a higher percentage of liver resections to be completed in a minimally invasive way with lower blood loss and a shorter LOS.

Pure robotic major hepatectomy with biliary reconstruction for hepatobiliary malignancies: first European results.

BACKGROUND: Combined liver and bile duct resection with biliary reconstruction for hepatobiliary malignancies are defined as highly complex surgical procedures. The robotic platform may overcome some major limitations of conventional laparoscopic surgery for these complex cases but its precise role is however still to be defined. METHODS: In our institution, patients requiring major hepatectomy with biliary reconstruction for malignancies were consecutively selected for minimally invasive robotic surgery from September 2020. All surgeries were undertaken using the da Vinci Xi Surgical System® (Intuitive Surgical, Sunnyvale, CA, USA). Intra-operative technique and postoperative outcome were analyzed. RESULTS: A total number of 10 patients (3 males and 7 females, median age 72 years) underwent robotic major hepatectomy and bile duct resection for hepatobiliary malignancies between September 2020 and March 2022. The indication for surgery was perihilar cholangiocarcinoma in 5 of 10 patients. Median operative time was 338 min and median blood loss was 110 mL. Postoperative length of stay was between 3 and 16 days (median: 9 days). There was no postoperative 90-day mortality. CONCLUSIONS: A robotic approach for hepatobiliary malignancies requiring combined major hepatectomy and bile duct resection seems feasible and safe in experienced hands.

Robotic biliary surgery for benign and malignant bile duct obstruction: a case series.

The majority of patients with benign or malignant biliary obstruction require surgical treatment with a bilio-enteric anastomosis. This requires fine dissection and advanced suturing. Robotic surgery may overcome some major limitations of conventional laparoscopic surgery. The precise role of robotic biliary surgery is, however, still to be defined. In our institution, patients requiring complex bile duct surgery were consecutively selected for minimally invasive robotic surgery from September 2020. All surgeries were undertaken using the da Vinci Xi Surgical System® (Intuitive Surgical, Sunnyvale, CA, USA). Intra-operative technique and postoperative outcome were analyzed. A total number of 14 patients underwent robotic biliary surgery for a variety of benign and malignant indications between September 2020 and May 2021. Six of fourteen patients (43%) had previous open abdominal surgery. Median blood loss was 25 mL (range 10-120 mL). There were no intra-operative complications and no conversions. Length of stay was between 3 and 11 days without major postoperative morbidity. Robotic surgery for benign and malignant bile duct obstruction is efficient and safe in experienced hands. Referral to a high-volume expert center is, however, advised.

Impact of resection margins for colorectal liver metastases in laparoscopic and open liver resection: a propensity score analysis.

BACKGROUND: There is no clear consensus over the optimal width of resection margin for colorectal liver metastases (CRLM), with evolving definitions alongside the advances on the management of the disease. In addition, data on the impact of resection margin after laparoscopic liver resection are still scarce. METHODS: Prospectively maintained databases of patients undergoing open or laparoscopic CRLM resection in 7 European tertiary hepatobiliary referral centres were reviewed. After propensity score matching (PSM), the influence of 1 mm and wider margins on OS and DFS were evaluated in open and laparoscopic cohorts. RESULTS: After PSM, 648 patients were comparable in each group. The incidence of positive margins (< 1 mm) was similar in open and laparoscopic groups (17% vs 13%, p = 0,142). Margins < 1 mm were associated with shorter RFS in open (12 vs 26 months, p = 0.042) and in laparoscopic group (13 vs 23, p = 0,002). Margins < 1 mm were associated with shorter OS in open (36 vs 57 months, p = 0.027), but not in laparoscopic group (49 vs 60, p = 0,177). Subgroups with margins ≥ 1 mm (1-4 mm, 5-9 mm, ≥ 10 mm) presented similar RFS in open (p = 0,251) or laparoscopic cohorts (p = 0.117), as well as similar OS in open (p = 0.295) or laparoscopic cohorts (p = 0.908). In the presence of liver recurrence, repeat liver resection was performed in 70 (30%) patients in the open group and 88 (48%) in the laparoscopic group (p < 0.001). CONCLUSIONS: Our study suggests that a positive resection margin (less than 1 mm) width does not impact OS after laparoscopic resection of CRLMs as it does in open liver resection. However, a positive margin continues to affect RFS in open and laparoscopic resection. Wider margins than 1 mm do not seem to improve oncological results in open or laparoscopic surgery.

Long-term survival and cure model following liver resection for breast cancer metastases.

INTRODUCTION: Long-term survival is still rarely achieved with current systemic treatment in patients with breast cancer liver metastases (BCLM). Extended survival after hepatectomy was examined in a select group of BCLM patients. PATIENTS AND METHODS: Hepatectomy for BCLM was performed in 139 consecutive patients between 1985 and 2012. Patients who survived < 5 years were compared to those who survived ≥ 5 years from first diagnosis of hepatic metastases. Predictive factors for survival were analyzed. Statistically cured, defined as those patients who their hazard rate returned to that of the general population, was analyzed. RESULTS: Of the 139, 43 patients survived ≥ 5 years. Significant differences between patient groups (< 5 vs. ≥ 5 years) were mean time interval between primary tumor and hepatic metastases diagnosis (50 vs. 43 months), mean number of resected tumors (3 vs. 2), positive estrogen receptors (54% vs. 79%), microscopic lymphatic invasion (65% vs. 34%), vascular invasion (63% vs. 37%), hormonal therapy after resection (34% vs. 74%), number of recurrence (40% vs. 65%) and repeat hepatectomy (1% vs. 42%), respectively. The probability of statistical cure was 14% (95% CI 1.4-26.7%) in these patients. CONCLUSIONS: Hepatectomy combined with systemic treatment can provide a chance of long-term survival and even cure in selected patients with BCLM. Microscopic vascular/lymphatic invasion appears to be a novel predictor for long-term survival after hepatectomy for BCLM and should be part of the review when discussing multidisciplinary treatment strategies.

Survival after associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) for advanced colorectal liver metastases: A case-matched comparison with palliative systemic therapy.

BACKGROUND: Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) allows the resection of colorectal liver metastases with curative intent which would otherwise be unresectable and only eligible for palliative systemic therapy. This study aimed to compare outcomes of ALPPS in patients with otherwise unresectable colorectal liver metastases with matched historic controls treated with palliative systemic treatment. METHODS: All patients with colorectal liver metastases from the international ALPPS registry were identified and analyzed. Survival data were compared according to the extent of disease. Otherwise unresectable ALPPS patients were defined by at least 2 of the following criteria: ≥6 metastasis, ≥2 future remnant liver metastasis, ≥6 involved segments excluding segment 1. These patients were matched with patients included in 2, phase 3, metastatic, colorectal cancer trials (CAIRO and CAIRO2) using propensity scoring in order to compare survival. RESULTS: Of 295 patients with colorectal liver metastases in the ALPPS registry, 70 patients had otherwise unresectable disease defined by the proposed criteria. Two-year overall survival was 49% and 72% for patients with ≥2 and <2 criteria, respectively (P = .002). Median disease-free survival was 6 months compared to 12 months (P < .001) in the ≥2 and <2 criteria groups, respectively. Median overall survival was comparable between ALPPS patients with ≥2 criteria and case-matched patients who received palliative treatment (24.0 vs 17.6 months, P = .088). CONCLUSION: Early oncologic outcomes of patients with advanced liver metastases undergoing ALPPS were not superior to results of matched patients receiving systemic treatment with palliative intent. Careful patient selection is essential in order to improve outcomes.

Predictive Profile-Nomogram for Liver Resection for Breast Cancer Metastases: An Aggressive Approach with Promising Results.

BACKGROUND: Breast cancer liver metastases (BCLM) are considered the most lethal compared with other sites of metastases in patients with breast cancer. This study aimed to evaluate the outcome after hepatectomy for BCLM within current multidisciplinary treatment and to develop a clinically useful nomogram to predict survival. METHODS: Between January 1985 and December 2012, 139 consecutive female patients underwent liver resection for BCLM at the authors' institution. Clinicopathologic data were collected and analyzed for survival outcome with determination of prognostic factors. A nomogram to predict survival was developed based on a multivariate Cox model. The predictive performance of the model was assessed according to the C-statistic and calibration plots. RESULTS: After a median follow-up period of 55 months, the overall 3- and 5-year survival rates after hepatectomy were respectively 58 and 47 %. The median overall survival period was 56 months, and the median disease-free survival period after surgical resection was 33 months. A single hepatic metastasis, no triple negative tumors, no microscopic vascular invasion, and perioperative hormonal or targeted therapy were related to improved overall survival. The model achieved good discrimination and calibration, with a C-statistic of 0.80. CONCLUSIONS: Liver resection for selected patients with breast cancer metastases can provide significant survival benefit. It should be part of a multidisciplinary treatment program in experienced liver surgery centers. The authors' nomogram facilitates personalized assessment of prognosis for these patients.

Postoperative peak transaminases correlate with morbidity and mortality after liver resection.

BACKGROUND: Transaminase levels are usually measured as markers of hepatocellular injury following liver resection, but recent evidence was unclear on their clinical value. This study aimed to identify factors that determine peak postoperative transaminase levels and correlated transaminase levels to postoperative complications. STUDY DESIGN: All liver resections performed at a single center between 2006 and 2015 were included in the analysis. Multivariate analysis was used to identify factors that determine peak ALT and AST levels and postoperative morbidity and mortality. An ALT and AST cutoff for the prediction of mortality was determined using receiver operating characteristic curves analysis. RESULTS: A total of 539 resections were included. Clavien-Dindo grade III or higher complications, intraoperative transfusion, and operative duration were identified as determinants of peak transaminases. A peak AST cut-off value for predicting mortality was defined at 828 U/L, with an area under the curve of 0.81 (0.73-0.89). The cut-off was an independent predictor of mortality (P < 0.01) along with (intraoperative) transfusion (P < 0.01), fifty-fifty criteria (P < 0.01), and age (P < 0.01). CONCLUSION: Postoperative transaminase levels are independent predictors of postoperative morbidity and mortality and therefore clinically relevant. Transaminase levels usually peak during the first 24 h after surgery and thus possess early prognostic power in terms of postoperative mortality.

Repeat Hepatectomy for Breast Cancer Liver Metastases.

BACKGROUND: Resection of breast cancer liver metastases (BCLM) combined with systemic treatment is increasingly accepted as a therapeutic option; however, the potential benefit of repeat hepatectomy for recurrent BCLM is unknown. METHODS: All consecutive female patients who underwent liver resection for BCLM at our center between January 1985 and December 2012 were included. Patients who had a single hepatectomy (N = 120) were compared with those who also underwent repeat hepatectomy (N = 19). Patients were selected for repeat hepatectomy based on operability and disease control. Prognostic factors of survival after repeat hepatectomy were determined. RESULTS: Median overall survival since first hepatectomy was 35 months, with a 3- and 5-year survival rate of 50 and 38 %, respectively. Overall survival following repeat hepatectomy was 64 and 46 % at 3 and 5 years, respectively. From the time of first hepatectomy, patients who underwent repeat hepatectomy had a better survival than those who had only one hepatectomy (95 and 84 vs. 50 and 38 % at 3 and 5 years, respectively) (p = 0.002). Median survival was 35 and 100 months, respectively, and median survival since the diagnosis of BCLM was 51 and 112 months in the single and repeat hepatectomy groups, respectively. Since the time of diagnosis, overall 3-, 5-, and 7-year survival rates were 75, 57, and 44 %, respectively, for all 139 patients. Improved overall survival after repeat hepatectomy was related to a time interval between breast cancer diagnosis and first hepatectomy of >2 years, a limited hepatectomy, solitary liver metastasis, positive progesterone receptor status, and chemotherapy following repeat hepatectomy. Patients with single BCLM at first hepatectomy had a 3- and 5-year overall survival rate of 76 and 76 % compared with 51 and 17 % in patients with multiple metastases (p = 0.023). CONCLUSION: In selected patients with BCLM, repeat hepatectomy for liver recurrence combined with systemic treatment provided survival rates comparable to those after first hepatectomy.

Complete resection of recurrent and initially unresectable dermatofibrosarcoma protuberans downsized by Imatinib.

Curative surgical treatment of recurrent, locally advanced dermatofibrosarcoma protuberans is often limited owing to a close relation of the tumor with important anatomical structures. Targeted therapy with imatinib, a tyrosine kinase inhibitor, may cause significant reduction of tumor volume, thereby enabling radical surgery. This treatment strategy, therefore, offers a chance of cure for selected patients with advanced dermatofibrosarcoma protuberans. In addition, preoperative treatment with imatinib may decrease possible disfigurement related to radical surgery for large tumors.

Sentinel lymph node mapping in colon cancer using radiocolloid as a single tracer: a feasibility study.

OBJECTIVE: Evaluation of the feasibility and safety of radiocolloid as a tracer for sentinel lymph node (SLN) mapping in colon cancer. METHODS: A feasibility study was conducted in consecutive colon cancer patients who were surgically treated at our institute. During preoperative colonoscopy, radiocolloid was injected around the tumour, followed by scintigraphic imaging to identify SLNs. SLNs were identified intraoperatively by a gamma probe and postoperatively by additional ex-vivo scintigraphy of the resection specimen. All retrieved SLNs were examined by histopathological ultrastaging. Standard oncologic laparoscopic resections with lymphadenectomy were performed following the identification of SLNs in all patients. RESULTS: Fourteen patients were included. At least one SLN was identified in 86% of patients. In one patient (7%) SLNs could be detected intraoperatively. In 83% of patients, the SLNs accurately reflected the tumour status of the remaining lymph nodes. Aberrant lymphatic drainage was preoperatively identified in one patient (7%), but this could not be confirmed intraoperatively. Sensitivity was 67% and the false-negative rate was 33%. Seventeen per cent of patients were upstaged because of SLN micrometastases. CONCLUSION: SLN mapping in colon cancer using radiocolloid as a single tracer is feasible and safe. However, it was difficult to identify SLNs intraoperatively because of high radioactivity at the injection site. Furthermore, the protocol is labour intensive, especially because of the additional colonoscopic tracer injection. Sensitivity is not better than when blue dye is used, and aberrant lymphatic drainage patterns are scarce. Therefore, this technique is not preferred for SLN mapping in colon cancer.

Short- and long-term results of extended left hepatectomy for colorectal metastases.

BACKGROUND: An extended left hepatectomy is a complex hepatic resection often performed for large tumours in close relationship to major hilar structures. Operative outcomes of this resection for colorectal liver metastases (CLM) remain unclear. The aim of the present study was to assess short- and long-term outcome for patients with CLM after an extended left hepatectomy. METHODS: A retrospective analysis of consecutive patients undergoing an extended left hepatectomy for CLM in a large, single-centre cohort between January 1990 and January 2006 was performed. RESULTS: Thirty-one patients (3.9%) from a consecutive series of 802 patients who had undergone hepatic resection were identified as having met the definition of an extended left hepatectomy and were included for further analysis. Maximum tumour size was more than 60 mm in 15 patients, with a median size of 67.5 mm for the total group (range: 20 to 160 mm). Twenty-six patients presented with initially unresectable metastases, related to large tumour size in 11 patients and to a close relation with major vascular structures in six patients. Preoperative chemotherapy was administered to 29 patients. Combined vascular resection was performed in five patients. The mortality rate at 90 days was zero and post-operative morbidity occurred in 17 patients. R0 and R1 resections were performed in 17 and 11 patients, respectively. Three- and 5-year overall survival was 38% and 27%, respectively. Disease-free survival was 9% and 4% at 3 and 5 years. Morbidity did not differ between patients with and without a caudate lobectomy (9 of 17 patients vs. 8 of 14 patients, respectively) (P= 0.815). CONCLUSIONS: An extended left hepatectomy for CLM can provide significant long-term survival. However, morbidity is increased in this complex procedure. A caudate lobectomy does not impact surgical outcome.

Impact of expanding criteria for resectability of colorectal metastases on short- and long-term outcomes after hepatic resection.

BACKGROUND: An expansion of resectability criteria of colorectal liver metastases (CLM) is justified provided "acceptable" short-term and long-term outcomes. The aim of the present study was to ascertain this paradigm in an era of modern liver surgery. METHODS: All consecutive patients who underwent hepatic resection for CLM at our institute between 1990 and 2010 were included in the study. Ninety-day mortality and morbidity rates were determined in the total study population and in 2 separate time periods (group I: 1990-2000; group II: 2000-2010). Similarly, overall and progression-free survival rates were determined. Independent predictors of postoperative morbidity were identified at multivariate analysis. RESULTS: Between 1990 and 2010, 1394 hepatectomies were performed in 1028 patients. Overall perioperative mortality and postoperative morbidity rates were 1.3% and 33%, respectively. Although patients in group II were older, had more often comorbid illnesses, and presented with more extensive liver disease, similar perioperative mortality rates were observed (1.1% in group I and 1.4% in group II; P = 0.53). A trend toward a higher morbidity rate was observed in group II (34% vs 31% in group I; P = 0.16). Independent predictors of postoperative morbidity were: treatment between 2000 and 2010, total hepatic ischemia time of 60 minutes or more, maximum size of CLM of 30 mm or more at histopathology, and presence of abnormalities in the nontumoral liver parenchyma. Although a trend toward lower overall survival was observed in patients with significant postoperative complications, no significant differences were observed in long-term outcomes between both treatment periods. CONCLUSION: After an aggressive multidisciplinary treatment of CLM, acceptable overall mortality and morbidity rates were observed. Perioperative mortality rates did not differ according to treatment period; however, more recently operated patients experienced more postoperative complications. These favorable short-term outcomes, without worsening of long-term outcomes, justify an expansion of the criteria for resectability in this patient category.

Regenerative nodular hyperplasia of the liver related to chemotherapy: impact on outcome of liver surgery for colorectal metastases.

BACKGROUND: Regenerative nodular hyperplasia (RNH) represents the end-stage of vascular lesions of the liver induced by chemotherapy. The goal was to evaluate its incidence and impact on the outcome of patients resected for colorectal liver metastases (CLM). METHODS: Patients who underwent hepatectomy for CLM after six cycles or more of first-line chemotherapy, between January 1990 and November 2006, were included. Detailed histopathologic analysis of the nontumoral liver was performed according to a standard format. RESULTS: From a cohort of 856 resected patients at our institution, 771 (90%) received preoperative chemotherapy. Of these, 146 fulfilled the selection criteria and were included: 24 (16%) received 5-fluorouracil (5-FU) and leucovorin (LV) alone, 92 (63%) had 5-FU/LV and oxaliplatin, 18 (12%) had 5-FU/LV and irinotecan, and 12 (8%) were treated by 5-FU/LV, oxaliplatin, and irinotecan. RNH occurred in 22 of 146 patients (15%). Twenty of these patients (91%) received oxaliplatin, of whom six (30%) had chronomodulated therapy. Patients treated by oxaliplatin more often had RNH compared with oxaliplatin-naïve patients (22 vs. 4%). Although operative mortality was nil, the presence of RNH was associated with increased postoperative hepatic morbidity (50 vs. 29%). Elevated preoperative gamma-glutamyltransferase (GGT) (>80 U/L; >1N) and total bilirubin levels (>15 µmol/L; >1N) were independent predictors of RNH. CONCLUSIONS: Patients with CLM who receive preoperative oxaliplatin have an increased risk of RNH and associated postoperative morbidity. Increased serum GGT and bilirubin are useful markers to predict the presence of RNH.

Incremental value of arterial and equilibrium phase compared to hepatic venous phase CT in the preoperative staging of colorectal liver metastases: an evaluation with different reference standards.

PURPOSE: To evaluate the incremental value of arterial and equilibrium phase compared to hepatic venous phase multidetector row CT (MDCT) in the preoperative staging of colorectal liver metastases (CLM) and to determine the influence of the reference standard. MATERIALS AND METHODS: Fifty-three consecutive CLM patients underwent 16 detector row CT in hepatic arterial, venous, and equilibrium phase before surgery between March 2003 and January 2007. Detected lesions were characterized by three independent radiologists. The reference standard consisted of intraoperative palpation and ultrasound of the liver, and histopathological examination of the resected specimen. Additionally, data of follow-up CT was added. Statistical analysis was performed on a per-lesion basis. RESULTS: According to the reference standard 251 lesions were present, of which 203 (81%) were malignant (mean size: 29.4 ± 22.5 mm), and 41 (16%) were benign (mean size: 8.3 ± 7.7 mm). Sensitivity rates for CLM were comparable between triphasic and hepatic venous phase CT (P>0.05). Sensitivity for the detection of CLM lowered from 60-77% to 52-68% when follow-up CT was added to the reference standard. CONCLUSION: Arterial and equilibrium phase CT have no incremental value compared to hepatic venous phase MDCT in the detection of CLM. Sensitivity rates are, however, influenced by the type of reference standard used.

Concomitant extrahepatic disease in patients with colorectal liver metastases: when is there a place for surgery?

OBJECTIVE: To evaluate the impact of the location of extrahepatic disease (EHD) on survival and to determine patient outcome in a consecutive series of patients with both intrahepatic and extrahepatic colorectal metastases treated by an oncosurgical approach, combining repeat surgery and chemotherapy. BACKGROUND: Although recognized as poor prognostic factor, concomitant EHD is no more considered an absolute contraindication to surgery in patients with colorectal liver metastases (CLM). However, the impact of the location of EHD on survival and the benefit in patient outcome is still diversely appreciated. METHODS: From 840 patients resected for CLM between 1990 and 2006, 186(22%) also had resectable EHD. Sequential surgery was routinely combined with perioperative chemotherapy. Survival was compared with that of patients without EHD, prognostic factors were identified, and a predictive model was designed to better select surgical candidates. RESULTS: Patients resected for CLM with concomitant EHD experienced a lower 5-year survival than those without EHD (28% vs 55%, P < 0.001). Five poor prognostic factors were identified at multivariate analysis: EHD-location other than lung metastases (5-year survival: 23% vs 33%, P = 0.02), EHD concomitant to CLM recurrence (14% vs 34%, P < 0.001), carcinoembryonic antigen level at least 10 ng/mL (16% vs 37%, P=0.02), at least 6 CLM(9% vs 32%, P = 0.02), and right colon cancer (P = 0.02). Five-year survival ranged from 64% (0 factors) to 0% (>3 factors). In the EHD group, patients with an EHD-recurrence experienced better outcomes when resected than those treated by chemotherapy alone (5-year survival: 38% vs 21%, P = 0.05). CONCLUSION: Although sequential surgery is warranted for patients with 5 or less CLM with isolated lung metastases, low carcinoembryonic antigen levels,and no right colon primary tumor, it should be questioned in the presence of more than 3 of these prognostic factors.

Tumor marker evolution: comparison with imaging for assessment of response to chemotherapy in patients with colorectal liver metastases.

BACKGROUND: As the real clinical significance of carcinoembryonic antigen (CEA) and carbohydrate antigen 19.9 (CA19.9) evolution during preoperative chemotherapy for colorectal liver metastases (CLM) is still unknown, we explored the correlation between biological and radiological response to chemotherapy, and their comparative impact on outcome after hepatectomy. METHODS: All patients resected for CLM at our hospital between 1990 and 2004 with the following eligibility criteria were included in the study: (1) preoperative chemotherapy, (2) complete resection of CLM, (3) no extrahepatic disease, and (4) elevated baseline tumor marker values. A 20% change of tumor marker levels while on chemotherapy was used to define biological response (decrease) or progression (increase). Correlation between biological and radiological response at computed tomography (CT) scan, and their impact on overall survival (OS) and progression-free survival (PFS) after hepatectomy were determined. RESULTS: Among 119 of 695 consecutive patients resected for CLM who fulfilled the inclusion criteria, serial CEA and CA19.9 were available in 113 and 68 patients, respectively. Of patients with radiological response or stabilization, 94% had similar biological evolution for CEA and 91% for CA19.9. In patients with radiological progression, similar biological evolution was observed in 95% of cases for CEA and in 64% for CA19.9. On multivariate analysis, radiological response (but not biological evolution) independently predicted OS. However, progression of CA19.9, but not radiological response, was an independent predictor of PFS. CONCLUSIONS: In patients with CLM and elevated tumor markers, biological response is as accurate as CT imaging to assess "clinical" response to chemotherapy. With regards to PFS, CA19.9 evolution has even better prognostic value than does radiological response. Assessment of tumor markers could be sufficient to evaluate chemotherapy response in a nonsurgical setting, limiting the need of repeat imaging.

Long-term outcomes after hepatic resection for colorectal metastases in young patients.

BACKGROUND: Long-term outcomes after hepatectomy for colorectal liver metastases in relatively young patients are still unknown. The aim of the current study was to evaluate long-term outcomes in patients < or = 40 years old, and to compare them with patients >40 years old. METHODS: All consecutive patients who underwent hepatectomy for colorectal liver metastases at the authors' hospital between 1990 and 2006 were included in the study. Patients < or = 40 years old were compared with all other patients treated during the same period. Overall survival (OS), progression-free survival (PFS), and disease-free survival (DFS) rates were determined, and prognostic factors were identified. RESULTS: In total, 806 patients underwent hepatectomy for colorectal liver metastases, of whom 56 (7%) were aged < or = 40 years. Among the young patients, more colorectal liver metastases were present at diagnosis, and they were more often diagnosed synchronous with the primary tumor. Five-year OS was 33% in young patients, compared with 51% in older patients (P = .12). Five-year PFS was 2% in young patients, compared with 16% in older patients (P < .001). DFS rates were comparable between the groups (17% vs 23%, P = .10). At multivariate analysis, age < or = 40 years was identified as an independent predictor of poor PFS. CONCLUSIONS: In young patients, colorectal liver metastases seem to be more aggressive, with a trend toward lower OS, more disease recurrences, and a significantly shorter PFS after hepatectomy. However, DFS rates were comparable between young and older patients, owing to an aggressive multimodality treatment approach, consisting of chemotherapy and repeat surgery. Therefore, physicians should recognize the poor outcome of colorectal liver metastases in young patients and should consider an aggressive approach to diagnosis and early treatment.

Patients with initially unresectable colorectal liver metastases: is there a possibility of cure?

PURPOSE: Although oncosurgical strategies have demonstrated increased survival in patients with unresectable colorectal liver metastases (CLM), their potential for cure is still questioned. The aim of this study was to evaluate long-term outcome after combining downsizing chemotherapy and rescue surgery and to define prognostic factors of cure. PATIENTS AND METHODS: All patients with initially unresectable CLM who underwent rescue surgery and had a minimum follow-up of 5 years were included. Cure was defined as a disease-free interval > or = 5 years from last hepatic or extrahepatic resection until last follow-up. RESULTS: Mean age of 184 patients who underwent resection (April 1988 through July 2002) was 56.9 years. Patients had a mean number of 5.3 metastases (bilobar in 76%), associated to extrahepatic disease in 27%. Surgery was possible after one (74%) or more (26%) lines of chemotherapy. Five- and 10-year overall survival rates were 33% and 27%, respectively. Of 148 patients with a follow-up > or = 5 years, 24 patients (16%) were considered cured (mean follow-up, 118.6 months), six (25%) of whom were considered cured after repeat resection of recurrence. Twelve "cured" patients (50%) had a disease-free interval more than 10 years. Cured patients more often had three or fewer metastases less than 30 mm (P = .03) responding to first-line chemotherapy (P = .05). Multivariate analysis identified maximum size of metastases less than 30 mm at diagnosis, number of metastases at hepatectomy three or fewer, and complete pathologic response as independent predictors of cure. CONCLUSION: Cure can be achieved overall in 16% of patients with initially unresectable CLM resected after downsizing chemotherapy. In addition to increased survival, this oncosurgical approach has real potential for disease eradication.

Long-term results of two-stage hepatectomy for irresectable colorectal cancer liver metastases.

OBJECTIVE: To assess feasibility, risks, and long-term outcome of 2-stage hepatectomy as a means to improve resectability of colorectal liver metastases (CLM). SUMMARY BACKGROUND DATA: Two-stage hepatectomy uses compensatory liver regeneration after a first noncurative hepatectomy to enable a second curative resection. METHODS: Between October 1992 and January 2007, among 262 patients with initially irresectable CLM, 59 patients (23%) were planned for 2-stage hepatectomy. Patients were eligible when single resection could not achieve complete treatment, even in combination with chemotherapy, portal embolization, or radiofrequency, but tumors could be totally removed by 2 sequential resections. Feasibility and outcomes were prospectively evaluated. RESULTS: Two-stage hepatectomy was feasible in 41 of 59 patients (69%). Eighteen patients failed to complete the second hepatectomy because of disease progression (n = 17) or bad performance status (n = 1). The 41 successfully treated patients had a mean number of 9.1 metastases (mean diameter, 48.5 mm at diagnosis). Chemotherapy was delivered before (95%), in between (78%), and after (78%) the 2 hepatectomies. Mean delay between the 2 liver resections was 4.2 months. Postoperative mortality was 0% and 7% (3/41) after the first and second hepatectomy, respectively. Morbidity rates were also higher after the second procedure (59% vs. 20%) (P < 0.001). Five-year survival was 31% on an intention to treat basis, and all but 2 patients who did not complete the 2-stage strategy died within 19 months. After a median follow-up of 24.4 months (range, 3.7-130.3), overall 3- and 5-year survivals for patients that completed both hepatectomies were 60% and 42%, respectively, after the first hepatectomy (median survival, 42 months from first hepatectomy and 57 months from metastases diagnosis). Disease-free survivals were 26% and 13% at 3 and 5 years, respectively. CONCLUSIONS: Two-stage hepatectomy provides a 5-year survival of 42% and a hope of long-term survival for selected patients with extensive bilobar CLM, irresectable by any other means.