Liver-first Approach Research Articles

Liver-First Resection in Patients With Synchronous Colorectal Liver Metastases Is Associated with Inferior Recurrence-Free Survival: Reconsidering the Importance of the Primary Cancer.

Synchronous colorectal liver metastases may be managed with primary-first, simultaneous, or liver-first resection. Relative oncologic outcomes based upon treatment sequencing are understudied. This study aimed to assess oncologic survival outcomes in patients with synchronous colorectal liver metastases managed with each of the three treatment strategies, with respect to early or delayed removal of the primary tumor. Retrospective analysis of prospectively maintained database, with 1:1 propensity-matching of relevant clinicopathologic variables comparing liver-first to primary-first/simultaneous approaches. Single-institution, tertiary cancer center. Patients undergoing curative-intent hepatectomy for synchronous colorectal liver metastases from 2003-2019. Overall and recurrence-free survival. Of 151 patients, 23% (n = 35) had liver-first and 77% (n = 116; primary-first = 93 and simultaneous = 23) had primary-first/simultaneous approaches. Median follow-up was 45 months. Recurrence-free survival was worse for liver-first versus primary-first/simultaneous groups (median 12 versus 16 months, p = 0.02), driven by three-year extrahepatic recurrence-free survival of 19%, 58%, and 50% for liver-first, primary-first, and simultaneous groups, respectively. Three-year overall survival was not significantly different at 86%, 79%, and 86%, respectively. Oncologic outcomes did not significantly differ between primary-first and simultaneous groups (all p > 0.4). Matching yielded 34 clinicopathologically similar patients per group (liver-first = 34, primary-first = 28/simultaneous = 6). The liver-first approach was associated with shorter recurrence-free survival (median 12 versus 23 months, p = 0.004), driven by extrahepatic recurrence-free survival (3-year: 20% versus 55%, p = 0.04). Overall survival was not significantly different at 3-years (79% versus 80%, p = 0.95) or 5-years (59% versus 59%, p > 0.99). This study has a retrospective design and limited sample size. A liver-first approach is associated with worse recurrence free-survival compared to primary-first or simultaneous resection, driven by extrahepatic recurrence. Prospective study of whether oncologic risk is associated with leaving the primary in situ is needed. Multidisciplinary treatment sequencing and enhanced postoperative surveillance for patients receiving liver-first resection is recommended. See Video Abstract.

Clinical Outcomes of the Liver-First Approach in the Management of Synchronous Colorectal Liver Metastases: A Retrospective Study

Clinical Outcomes of the Liver-First Approach in the Management of Synchronous Colorectal Liver Metastases: A Retrospective Study

Feasibility and Short-Term Outcomes in Liver-First Approach: A Spanish Snapshot Study (the RENACI Project).

(1) Background: The liver-first approach may be indicated for colorectal cancer patients with synchronous liver metastases to whom preoperative chemotherapy opens a potential window in which liver resection may be undertaken. This study aims to present the data of feasibility and short-term outcomes in the liver-first approach. (2) Methods: A prospective observational study was performed in Spanish hospitals that had a medium/high-volume of HPB surgeries from 1 June 2019 to 31 August 2020. (3) Results: In total, 40 hospitals participated, including a total of 2288 hepatectomies, 1350 for colorectal liver metastases, 150 of them (11.1%) using the liver-first approach, 63 (42.0%) in hospitals performing <50 hepatectomies/year. The proportion of patients as ASA III was significantly higher in centers performing ≥50 hepatectomies/year (difference: 18.9%; p = 0.0213). In 81.1% of the cases, the primary tumor was in the rectum or sigmoid colon. In total, 40% of the patients underwent major hepatectomies. The surgical approach was open surgery in 87 (58.0%) patients. Resection margins were R0 in 78.5% of the patients. In total, 40 (26.7%) patients had complications after the liver resection and 36 (27.3%) had complications after the primary resection. One-hundred and thirty-two (89.3%) patients completed the therapeutic regime. (4) Conclusions: There were no differences in the surgical outcomes between the centers performing <50 and ≥50 hepatectomies/year. Further analysis evaluating factors associated with clinical outcomes and determining the best candidates for this approach will be subsequently conducted.

A Liver-First Approach Using Ablation for Oligometastatic Pancreatic Cancer: A Report of a Successful Case

A Liver-First Approach Using Ablation for Oligometastatic Pancreatic Cancer: A Report of a Successful Case

Treatment of locally advanced rectal cancer and synchronous liver metastases: multicentre comparison of two treatment strategies.

Management of locally advanced rectal cancer (LARC) has been optimized during recent times through (beyond) total mesorectal excision surgery and, more recently, the introduction of total neoadjuvant treatment (TNT)1–4. For patients with synchronous liver metastases, the optimal treatment strategy is less clear, with high variability among institutions worldwide5. In the Netherlands, two specific treatment sequences have mainly been used for treating LARC and synchronous liver metastases: the liver-first approach (LFA) and the M1 schedule6–8. The LFA consists of induction systemic chemotherapy, subsequent local treatment of the liver metastases, followed by long-course (chemo)radiotherapy and resection of the primary tumour. The rationale behind LFA is to treat the rectal tumour locally only when control of synchronous liver metastases has been established. Radiotherapy and primary tumour resection can be avoided in patients with disease progression during the first phase of the schedule9. The M1 schedule starts with preoperative short-course pelvic radiotherapy (5 × 5 Gy), followed by systemic therapy, and subsequent surgical treatment of both the liver and rectum (either simultaneously, liver first or primary tumour first). The advantage of starting with radiotherapy is the immediate downstaging effect on the primary tumour. This strategy has been proven safe and effective, and leads to excellent local control10.

Textbook Outcomes in the Liver-first Approach

Textbook Outcomes in the Liver-first Approach

Are the Short-term Results of Liver-first Approach Different Depending on the Location of the Primary?

Are the Short-term Results of Liver-first Approach Different Depending on the Location of the Primary?

A comparison of the simultaneous, liver-first, and colorectal-first strategies for surgical treatment of synchronous colorectal liver metastases at two major liver-surgery institutions in Sweden

BackgroundThe optimal treatment strategy for patients with synchronous colorectal liver metastases (CRLM) is unclear. The aim of this study was to compare the outcome of the simultaneous, liver-first, and colorectal-first surgical approaches. MethodsAll consecutive patients who had been resected with curative intent for CRLM were included. A Cox regression model was constructed, and an intention-to-treat analysis was performed between the liver-first and the simultaneous approaches, after propensity score matching. Results658 patients were included in the analysis. 92 patients had a simultaneous resection, 163 patients had liver-first, and 403 patients had a colorectal-first approach. Overall survival was 54.9 months (95% CI 39.2–70.4) in the liver-first group, 54.5 months (95% CI 46.8–62.3) in colorectal-first group, and 59.6 months (95% CI 42.2–77.0) in the simultaneous group (log-rank p =0.850). In the matched cohort there were no differences in Clavien-Dindo 3a (p = 0.992) or 3b and greater (p = 0.999). Median overall survival was for liver-first group 42.2 months (95% CI 26.3–58.2), and for the simultaneous group 56.2 months (95% CI 47.1–65.4) (stratified log-rank p = 0.455). ConclusionA simultaneous approach was not associated with worse overall survival or morbidity compared to a liver-first approach.

Análisis retrospectivo de los resultados a largo plazo de la estrategia inversa en pacientes con cáncer colorrectal y enfermedad hepática metastásica sincrónica avanzada

BackgroundThe “liver-first” approach (LFA) is a strategy indicated for advanced synchronous liver metastases (ASLM) from colorectal cancer (CRC). Includes neoadjuvant chemotherapy, resection of the ASLM followed by CRC resection. MethodsRetrospective descriptive analysis from a prospective database of hepatectomies from liver metastases (LM) from CRC in two centers. Between 2007-2019, 88 patients with CRC-ASLM were included in a LFA scheme. Bilobar (LM) was present in 65.9%, the mean number of lesions was 5.5 and mean size 42.7mm. Response to treatment was assessed by RECIST criteria. Progression-free survival (PFS) and overall survival (OS) were estimated using Kaplan-Meier survival curves. ResultsSeventy-five of 88 patients (85.2%) completed the LFA. RECIST evaluation showed partial response in 75.7% and stable disease in 22.8%. Severe morbidity rate (Clavien–Dindo ≥ IIIA) after liver and colorectal surgery was present in 29.4% and 9.3%, respectively. There was no 90-day postoperative mortality in both liver and colorectal surgeries. Recurrence rate was 76%, being the liver the most frequent site, followed by the pulmonary. From the total number of recurrences (106) in 56 patients, surgical with chemotherapy rescue treatment was accomplished in 34 of them (32.1%). The mean PFS was 8.5 and 5-year OS was 53%. ConclusionsIn patients with CRC-ASLM the LFA allows control of the liver disease beforehand and an assessment of the tumor response to neoadjuvant chemotherapy, optimising the chance of potentially curative liver resection, which influences long-term survival.

Minor versus Major Hepatectomy in Simultaneous Operation with Rectal Cancer: Is it Comparable in Terms of Oncological Outcomes?

Background: Hepatectomy in simultaneous operation with rectal cancer is technically challenging. It is feasible and safe in selected patients when the operations are performed in experienced centers. However, oncological outcomes of this operation have been inconclusive, especially in the type of hepatectomy that is combined with rectal cancer surgery. Objective: To evaluate the perioperative and oncological outcomes of minor and major hepatectomy in simultaneous operation with rectal cancer. Materials and Methods: Patients with synchronous rectal cancer with liver metastasis that underwent simultaneous resection between October 2005 and October 2019 were enrolled into the present study. The patients were divided into two groups, major and minor hepatectomy. Clinicopathological characteristics and surgical outcomes including complications, overall survival (OS) and progression-free survival (PFS) between the two groups were analyzed. Results: Seventy-two patients, which included 54 patients in the minor hepatectomy group and 18 patients in the major hepatectomy group, were included in the present study. A comparative analysis of patient and tumor characteristics between the two groups found that the CEA level (p=0.023), the number (p=0.010), and size of liver metastasis (p=0.006) were higher in the major hepatectomy group. There was no difference in both minor and major complication rates between the two groups. The OS and PFS rates were significantly better in the minor hepatectomy group compared to the major hepatectomy group at 50.23 versus 24.03 months (p&lt;0.001 and 21.60 versus 15.73 months (p=0.015), respectively. Multivariate analysis showed that primary tumor staging, diabetes, and major hepatectomy impacted both OS and PFS. Conclusion: Minor hepatectomy in simultaneous operation with rectal cancer provides more favorable oncological outcomes. In case of rectal cancer associated with high tumor burden of liver metastasis, which required major hepatectomy, stage operation with either rectal-first or liver-first approach is more appropriate. Keywords: Rectal cancer; Synchronous liver metastasis; Simultaneous operation

Long-term results of liver-first approach strategy in patients with advanced synchronous liver metastases from colorectal cancer

BackgroundThe “liver-first” approach (LFA) is a strategy indicated for advanced synchronous liver metastases (ASLM) from colorectal cancer (CRC). Includes neoadjuvant chemotherapy, resection of the ASLM followed by CRC resection. MethodsRetrospective descriptive analysis from a prospective database of hepatectomies from liver metastases (LM) from CRC in two centers. Between 2007–2019, 88 patients with CRC-ASLM were included in a LFA scheme. Bilobar (LM) was present in 65.9%, the mean number of lesions was 5.5 and mean size 42.7 mm. Response to treatment was assessed by RECIST criteria. Progression-free survival (PFS) and overall survival (OS) were estimated using Kaplan–Meier survival curves. ResultsSeventy-five of 88 patients (85.2%) completed the LFA. RECIST evaluation showed partial response in 75.7% and stable disease in 22.8%. Severe morbidity rate (Clavien–Dindo ≥ IIIA) after liver and colorectal surgery was present in 29.4% and 9.3%, respectively. There was no 90-day postoperative mortality in both liver and colorectal surgeries. Recurrence rate was 76%, being the liver the most frequent site, followed by the pulmonary. From the total number of recurrences (106) in 56 patients, surgical with chemotherapy rescue treatment was accomplished in 34 of them (32.1%). The mean PFS was 8.5 and 5-year OS was 53%. ConclusionsIn patients with CRC-ASLM the LFA allows control of the liver disease beforehand and an assessment of the tumor response to neoadjuvant chemotherapy, optimising the chance of potentially curative liver resection, which influences long-term survival.

First in Poland Simultaneous Liver-Lung Transplantation With Liver-First Approach for Recipient Due to Cystic Fibrosis: A Case Report

Cystic fibrosis is an autosomal progressive disease affecting the lung, pancreas, and liver. Some patients develop end-stage respiratory and liver failure. For such patients, combined lung-liver transplantation remains the only therapeutic option. In this article we present the first simultaneous lung-liver transplantation in Poland, as well as in Central and Eastern Europe, with detailed clinical history, surgical aspects, and postoperative course.

The optimal treatment sequence for patients with stage IV rectal cancer and limited liver metastases: a nationwide comparison of two strategies.

Background: In the Netherlands, different treatments sequences are used for rectal cancer patients with resectable synchronous liver metastases. Two common sequences used are the M1-scheme (M1) and the liver-first approach (LF). The aim of this study was to compare the oncological outcomes of patients treated with M1 and LF.

Which surgical strategy for colorectal cancer with synchronous hepatic metastases provides the best outcome? A comparison between primary first, liver first and simultaneous approach.

There is no clear consensus about the best surgical strategy for patients with colorectal cancer (CRC) and synchronous liver metastases (SCRLM). Between 2009 and 2019, patients with CRC and SCRLM considered for curative treatment were included. Perioperative and follow-up data were analysed to examine the safety and survival outcomes of primary first (PF), liver first (LF) and simultaneous resection (SR) strategies. 204 patients were identified, consisting of PF (n = 129), LF (n = 26) and SR (n = 49). Forty-five patients (22.1%) failed to have either the primary or the liver metastases resected following initial LF (n = 11, 42.3%) or PF (n = 34, 26.4%), respectively (p < 0.001). The postoperative morbidity rates were 31.0%, 38.4% and 40.8% in PF, LF and SR group, respectively (p = 0.409); the mortality rates were 2.3%, 0% and 4.1%, respectively (p = 0.547). The 1-, 3- and 5-year overall survival (OS) were 94%, 72%, 53% in the PF group, 74%, 54%, 36% in the LF group, and 91%, 74%, 63% in the SR group. LF group had the worst OS compared to PF and SR (p = 0.040, p = 0.052). The 1-, 3- and 5-year disease-free survival (DFS) were 31%, 15%, 10% in PF, 21%, 9% and 9% in LF and 45%, 28% and 28% in SR group, respectively. SR group had a better DFS compared to PF and LF (p = 0.005, p = 0.008). At the multivariate analysis, there was no difference between the three strategies in terms of OS (PF vs SR OS-HR 1.090, p = 0.808; LF vs SR OS-HR 1.582, p = 0.365) and the PF had a worse DFS compared to the SR approach (PF vs SR DFS-HR 1.803, p = 0.007; LF vs SR DFS-HR 1.252, p = 0.492). PF, LF and SR had comparable postoperative morbidity and mortality. The three surgical strategies had similar OS outcomes. The PF strategy was associated with a worse DFS than SR, while the LF approach was associated with a high failure rate to progress to the second stage (primary tumour resection).

Liver First Approach for Synchronous Colorectal Liver Metastasis: Is First Approach the Best Approach?

Introduction: Liver first approach (LFA) for synchronous colorectal liver metastasis (CRLM) is an upcoming strategy for improving survival among patients with stage IV colorectal carcinoma. We share our experience of managing such patients using the LFA and their treatment outcome. Methods: We retrospectively studied 1038 patients who presented with synchronous CRLM over a 10 year period. The clinical history, management strategy and outcomes of patients undergoing the LFA were analysed in detail. Results: We formulated an algorithm for management of patients presenting with synchronous CRLM (picture). Out of 1038 such patients, 31 were selected for the LFA. 29 recto-sigmoid, one caecal and one descending colon carcinoma were part of the LFA group. All of them underwent neo-adjuvant short course radiotherapy with systemic chemotherapy and proceeded to have liver resection. Following this, 11 patients had disease progression and only 20 (64.5%) proceeded to have their primary tumor resected. The peri-operative characteristics and outcomes of patients who completed the LFA are listed in the table below. Among the patients who completed the LFA, the recurrence rate was 70% (n=14) and the median time to recurrence was 418.5 days (IQR 407). The 1-year, 3-year and 5-year survival rates for the LFA were 90%, 85% and 65% respectively, with a median survival of 1112.5 days (IQR 1025) which is similar to the conventional methods. Conclusions: LFA for synchronous CRLM better serves patients when appropriately selected and combined with a multi-modality approach especially in patients with a large disease burden in the liver.Tabled 1Demographics Mean age60.77 years Male : Female ratio13 : 7Tumor characteristics Primary locationRectum 19, Caecum 1 Average number of liver metastasis3.85 Average size of largest metastasis49.8 mm Bilobar liver metastasis11 (55%)Hepatic resection Right hepatectomy5 Right hepatectomy with non-anatomical resections3 Non-anatomical resection3 Extended left hepatectomy3 Extended right hepatectomy1 Left lateral sectionectomy2 Left hepatectomy with right posterior sectionectomy1 Central hepatectomy2Post hepatic resection Major morbidity (Clavien Dindo ≥3b)1 (5%) Mortality0 R1 margin5 (25%)Colorectal resection Anterior resection15 Abdomino-perineal resection4 Right hemicolectomy1Post colorectal resection Major morbidity (Clavien Dindo ≥3b)3 (15%) Mortality2 (10%) Open table in a new tab

Long-Term Results of Liver-First Approach Strategy in Patients with Advanced Synchronous Liver Metastases from Colorectal Cancer

Background: The ‘‘liver-first” approach (LFA) is a strategy indicated for advanced synchronous liver metastases (ASLM) from colorectal cancer (CRC). Includes resection of the ASLM before the primary tumor after neoadjuvant chemotherapy. Methods: Retrospective descriptive analysis from a prospective database of hepatectomies from liver metastases (LM) from CRC in two centers. Between 2007-2019, from the total of hepatectomies performed (609), 88 patients with CRC-ASLM were included in a LFA scheme. Bilobar (LM) was present in 65.9%, the mean number of lesions was 5.5 and mean size 42.7mm. Response to treatment was assessed by RECIST classification. Progression-free survival (PFS) and overall survival (OS) were estimated using Kaplan-Meier survival curves. Results: 75 of 88 patients (85.2%) completed the LFA. RECIST evaluation showed partial response in 75.7% and stable disease in 22.8%. Severe morbidity rate (Clavien–Dindo ≥ IIIA) after liver and colorectal surgery was present in 29.4% and 9.3%, respectively. There was no 90-day postoperative mortality in both liver and colorectal surgeries. Recurrence rate was 76%, being the liver the most frequent site, followed by the pulmonary. From the total number of recurrences (106) in 56 patients, surgical with or without chemotherapy rescue treatment was accomplished in 34 of them (32.1%). The mean PFS and OS was 8.6 and 41.2 months, respectively. Conclusions: In patients with CRC-ASLM the LFA is feasible and safe. It allows control of the liver disease beforehand and an assessment of the tumor response to neoadjuvant chemotherapy, optimizing the chance of potentially curative liver resection, which influences long-term survival.

Roboticky asistovaná léčba zhoubných nádorů kolorekta a hepatopankreatobiliární oblasti

Summary: Introduction: The Czech Republic belongs to countries under significant strain due to malignant tumours. Despite the changes introduced in the therapy of gastrointestinal malignancies, radical removal of the tumour holds a crucial position in the mutimodal therapeutic process and is irreplaceable nowadays. From the beginning of the third millennium, minimally invasive surgery of abdominal tumours is being expanded with robotic-assisted procedures. The aim of this paper is to assess the benefits of robotic-assisted surgery in the treatment of colorectal and hepatopancreatobiliary neoplasms and to present the results of a non-randomized study with prospectively collected data from robotically assisted rectal cancer surgeries. Material and method: The authors summarize studies published in the PubMed, EMBASE, Medline and Cochrane Library databases that compare robotic and laparoscopic approaches in the treatment of colorectal and hepatopancreatobiliary malignancies, and present the results of their own non-randomized study. 204 patients with rectal cancer (&lt;15 cm from the anal verge) who underwent robotic-assisted surgery at our department between 1 January 2016 and 31 December 2020 were included in the study. All demographic, clinical and oncological data were prospectively obtained and analysed. The data were analysed using descriptive statistic methods. Results: 204 patients with rectal cancer of whom 138 were men and 66 were women underwent robotic surgery at our department during the five-year period. In 97 (47.5%) cases the disease was dia­gnosed in an advanced stage (stage III and IV of the TNM classification). 18 patients had synchronous liver metastases and 2 patients had pulmonary metastases at the time of the dia­gnosis. The liver-first approach was indicated in 8 (44.4%) patients, two patients underwent a radical resection of liver lesions together with the primary neoplasm in one surgery. Total mesorectal excision was performed in 136 patients with extraperitoneal disease, partial mesorectal excision was performed in 68 cases. 18 complications were documented. Clinically relevant anastomotic leak requiring intervention occurred in 5 (3.6%) cases. One patient died due to decompensation of chronic toxonutritive liver disease. Local recurrence was documented in 6 patients, half of them underwent radical resection. Conclusion: Surgical therapy holds a crucial position in the treatment of colorectal and hepatopancreatobiliary neoplasms and represents the only potentially curative procedure in multimodal therapy. Robotic-assisted therapy has become a routine therapeutic modality for colorectal and hepatopancreatobiliary malignancies worldwide. Da Vinci assisted surgeries prevail in the surgical treatment of rectal cancer at the authors’ workplace as well as at some foreign centres. Compared to open and laparoscopic resections of rectal carcinoma, robotic-assisted operations achieve the same clinical and oncological results with a lower rate of complications. Key words: robotic surgery – colorectal cancer – liver malignancies – pancreatic carcinoma

The liver-first approach for synchronous colorectal liver metastases: A systematic review and meta-analysis of completion rates and effects on survival.

Patients presenting with synchronous colorectal liver metastases are increasingly being considered for a curative treatment, and the liver-first approach is gaining popularity in this context. However, little is known about the completion rates of the liver-first approach and its effects on survival. A systematic review and meta-analysis of liver-first strategy for colorectal liver metastasis. The primary outcome was an assessment of the completion rates of the liver-first approach. Secondary outcomes included overall survival, causes of non-completion, and clinicopathologic data. Seventeen articles were amenable for inclusion and the total study population was 1041. The median completion rate for the total population was 80% (range 20-100). The median overall survival for the completion and non-completion groups was 45 (range 12-69) months and 13 (range 10.5-25) months, respectively. Metadata showed a significant survival benefit for the completion group, with a univariate hazard ratio of 12.0 (95% confidence interval, range 5.7-24.4). The major cause of non-completion (76%) was liver disease progression before resection of the primary tumor. Pearson tests showed significant negative correlation between median number of lesions and median size of the largest metastasis and completion rate. The liver-first approach offers a complete resection to most patients enrolled, with an overall survival benefit when completion can be assured. One-fifth fails to return to intended oncologic therapy and the major cause is interim metastatic progression, most often in the liver. Risk of non-completion is related to a higher number of lesions and large metastases. The majority of studies stem from primary rectal cancers, which may influence on the return to intended oncologic therapy as well.PROSPERO id no: 170459.

Liver-first approach for synchronous metastatic colorectal cancer

Liver-first approach for synchronous metastatic colorectal cancer

ASO Author Reflections: The Liver-First Approach: A New Standard for Patients with Multiple Bilobar Colorectal Metastases?

ASO Author Reflections: The Liver-First Approach: A New Standard for Patients with Multiple Bilobar Colorectal Metastases?