Disappearing Liver Metastases Research Articles

The High Incidence of Occult Carcinoma in Total Hepatectomy Specimens of Patients Treated for Unresectable Colorectal Liver Metastases With Liver Transplant.

To describe the rate of occult carcinoma deposits in total hepatectomy specimens from patients treated with liver transplant (LT) for colorectal liver metastases (CRLM). Previous studies have shown that patients with CRLM treated with systemic therapy demonstrate a high rate of complete radiographic response or may have disappearing liver metastases. However, this does not necessarily translate into a complete pathologic response, and residual invasive cancer may be found in up to 80% of the disappearing tumors after resection. Retrospective review of 14 patients who underwent LT for CRLM, at 2 centers. Radiographic and pathologic correlation of the number of tumors and their viability before and after LT was performed. The median (interquartile range) number of tumors at diagnosis was 11 (4-23). The median number of chemotherapy cycles was 24 (16-37). Hepatic artery infusion was used in 5 patients (35.7%); 6 (42.9%) underwent surgical resection, and 5 (35.7%) received locoregional therapy. The indication for LT was unresectability in 8 patients (57.1%) and liver failure secondary to oncologic treatment in the remaining 6 (42.9%). Before LT, 7 patients (50%) demonstrated fluorodeoxyglucose-avid tumors and 7 (50%) had a complete radiographic response. Histopathologically, 11 patients (78.6%) had a viable tumor. Nine (64.2%) of the 14 patients were found to have undiagnosed metastases on explant pathology, with at least 22 unaccounted viable tumors before LT. Furthermore, 4 (57.1%) of the 7 patients who demonstrated complete radiographic response harbored viable carcinoma on explant pathology. A complete radiographic response does not reliably predict a complete pathologic response. In patients with unresectable CRLM, total hepatectomy and LT represent a promising treatment options to prevent indolent disease progression from disappearing CRLM.

Disappearing colorectal liver metastases in the era of state-of-the-art triple-modality diagnostic imaging

IntroductionSystemic therapy can result in disappearance of colorectal liver metastases in up to 40% of patients. This might be an overestimation caused by suboptimal imaging modalities. The aim of this study was to investigate the use of imaging modalities and the incidence, management and outcome of patients with disappearing liver metastases (DLMs). MethodsThis was a retrospective study of consecutive patients treated for colorectal liver metastases at a high volume hepatobiliary centre between January 2013 and January 2015 after receiving induction or neoadjuvant systemic therapy. Main outcomes were use of imaging modalities, incidence, management and longterm outcome of patients with DLMs. ResultsOf 158 patients included, 32 (20%) had 110 DLMs. Most patients (88%) had initial diagnostic imaging with contrast enhanced-CT, primovist-MR and FDG-PET and 94% of patients with DLMs were restaged using primovist-MR. Patients with DLMs had significantly smaller metastases and the median initial size of DLMs was 10 mm (range 5–61). In the per lesion analysis, recurrence after “watch & wait” for DLMs occurred in 36%, while in 19 of 20 resected DLMs no viable tumour cells were found. Median overall (51 vs. 28 months, p < 0.05) and progression free survival (10 vs. 3 months, p = 0.003) were significantly longer for patients with DLMs. ConclusionEven state-of-the-art imaging and restaging cannot solve problems associated with DLMs. Regrowth of these lesions occurs in approximately a third of the lesions. Patients with DLMs have better survival.

Assessment of the response to systemic treatment of colorectal liver metastases on cross-sectional imaging - a systematic review.

Colorectal cancer (CRC) is one of the most common malignancies in the world. Nowadays many treatments are available to help control CRC, including surgery, radiation therapy, interventional radiology, and drug treatments. A multidisciplinary approach and the role of radiologists is needed to assist the surgeon in the management thanks to emerging technology and strategies. The Response Evaluation Criteria in Solid Tumours (RECIST) has been created to objectify and standardize cancer response assessment. Thus, in this article specific presumptions and practical aspects of evaluating responses according to the RECIST 1.1 are discussed. Furthermore, examples of possible response to systemic treatment of colorectal liver metastases (CRLM), including tumour necrosis, apparent diffusion coefficient (ADC) values, tumour calcification, tumour fibrosis and intratumoural fat deposition observed on cross-sectional imaging, are described. Disappearing liver metastases (DLM) presents a therapeutic dilemma. The optimal management of DLM remains controversial due to the uncertainty of residual microscopic disease and effective long-term outcomes. The article provides an overview of the CRLM phenomenon and current possible assessment methods of the response to systemic treatment.

Disappearing Colorectal Liver Metastases: Do We Really Need a Ghostbuster?

The development of new systemic treatment strategies has resulted in a significant increase in the response rates of colorectal liver metastases (CRLM) in the last few years. Although the radiological response is a favorable prognostic factor, complete shrinkage of CRLM, known as disappearing liver metastases (DLM), presents a therapeutic dilemma, and proper management is still debated in the literature. In fact, DLM is not necessarily equal to cure, and when resected, pathological examination reveals in more than 80% of patients a variable percentage of the tumor as residual disease or early recurrence in situ. Moreover, while a higher incidence of intrahepatic recurrence is documented in small series when surgery is avoided, its clinical significance for long-term OS is still under investigation. In light of this, a multidisciplinary approach and, in particular, radiologists’ role is needed to assist the surgeon in the management of DLM, thanks to emerging technology and strategy. Therefore, the aim of this review is to provide an overview of the DLM phenomenon and current management.

Disappearing Colorectal Liver Metastases in the Era of State-of-The-Art Triple-Modality Diagnostic Imaging with CT, MR and FDG-PET

Introduction: Systemic therapy can result in the disappearance of colorectal liver metastases (CRLM) in up to 40% of patients. This might be an overestimation caused by suboptimal imaging modalities. The aim of this study was to investigate the use of imaging modalities and the incidence, management and outcomes of patients with disappearing liver metastases (DLMs). Method: This retrospective study from a high-volume hepatobiliary center investigated 158 consecutive patients with CRLM undergoing systemic therapy for induction or as neoadjuvant treatment in 2013 and 2014. Main outcomes were the use of imaging modalities, incidence, management and long-term outcomes of patients with DLMs. Results: 110 DLMs were seen in 32 (20%) patients. The majority of patients (88%) had initial diagnostic imaging with contrast enhanced-CT, primovist-MR and FDG-PET and 94% of patients with DLMs were restaged using primovist-MR. Patients with DLMs had significantly smaller metastases and the median initial size of DLMs were 10 mm (range 5–61). In the per lesion analysis, recurrence after watch & wait for DLMs occurred in 64%, while in 19 of 20 resected DLMs no viable tumour cells were found. Median overall (46 vs 26 months) and progression free survival (12 vs 3 months) were significantly longer for patients with DLMs. Conclusions: With the use of triple modality imaging and restaging with primovist-MR the incidence of DLMs remains 20%, indicating that optimal imaging techniques are not an important factor causing DLMs. Response to therapy, as reflected by DLMs, influences survival of patients with colorectal liver metastases.

Clinical research progress on disappearing colorectal liver metastases

Colorectal cancer is currently one of the most common digestive system tumors, and the liver is the most common metastatic site of colorectal cancer. In recent years, with the continuous development of the multidisciplinary treatment for colorectal cancer patients, there are quite a few cases of disappearing liver metastases (DLM) after receiving preoperative chemotherapy (or combined targeted drug therapy), and the diagnosis and treatment of DLM is currently still a very challenging and controversial topic. This article sorts out the related researches on DLM in recent years, mainly including the following 4 aspects: (1) The factors associated with DLM, including the size and number of liver metastases, chemotherapy regimens and cycles, targeted therapy drugs, and the pattern of liver metastases, Ras/Braf status and the location of the primary lesion. (2) The relationship between DLM and true complete response (pathological complete response and persistent clinical complete response), and the related predictive factors of pathological complete response. (3) Clinical evaluation of DLM: preoperative evaluation includes ultrasound, CT, MRI, and PET, while intraoperative evaluation includes intraoperative exploration, intraoperative ultrasound, and augmented reality. (4) DLM treatment strategies, including surgical treatment, local treatment, non-surgical treatment and individualized treatment.

When is a Ghost Really Gone? A Systematic Review and Meta-analysis of the Accuracy of Imaging Modalities to Predict Complete Pathological Response of Colorectal Cancer Liver Metastases After Chemotherapy.

Administration of chemotherapy to patients with colorectal liver metastases may result in disappearing liver metastases (DLM). This poses a therapeutic dilemma due to the uncertainty of true complete (pathological) response. We aimed to examine the diagnostic performance of imaging modalities in detecting true complete response in patients with DLM after chemotherapy. We performed a systematic search for articles assessing the diagnostic performance of imaging modalities in evaluating DLM following chemotherapy. True complete response was defined as 1-year recurrence-free survival in non-resected patients or complete pathological response on histologic examination in resected patients. We calculated the negative predictive value (NPV) for detecting true complete response of each imaging modality using a random effects model. Thirteen studies comprising 332 patients with at least one DLM were included. The number of DLMs after chemotherapy was 955 withcomputed tomography (CT), 104 withpositron emission tomography (PET), 50with intraoperative ultrasound (IOUS), 585with magnetic resonance imaging (MRI), and 175 withcontrast-enhanced IOUS (CEIOUS). Substantial variation in study design, patient characteristics, and imaging features was observed. Pooled NPV was 0.79 (95% confidence interval [CI] 0.53-0.96), 0.73 (95% CI 0.58-0.85), 0.54 (95% CI 0.37-0.7), 0.47 (95% CI 0.34-0.61), and 0.22 (95% CI 0.11-0.39) for CEIOUS, MRI, IOUS, CT, and PET, respectively. After chemotherapy, MRI or CEIOUS are the most accurate imaging modalities for assessment of DLM and should be used routinely in this context. Given the high NPV of these two modalities, surgical resection of visible CRLM is warranted if technically possible, even if DLM remain.

ASO Author Reflections: Disappearing Liver Metastases: Should We Be Afraid of the Dark?

ASO Author Reflections: Disappearing Liver Metastases: Should We Be Afraid of the Dark?

Implementing Integrated Quality Assurance (SURCARE) for EORTC-JCOG 1527 / ESSO 02: Diffusion-Weighted Magnetic Resonance Imaging (DW-MRI) Assessment of Liver Metastasis to Improve Surgical Planning (DREAM)

For patients with initially unresectable colorectal liver metastases (CRLM) with good clinical response to chemotherapy, the presence of disappearing liver metastases (DLMs) diagnosed by CT is a major independent prognostic factor. However, correlation between radiological and pathological complete response has not been fully investigated using the latest imaging and pathology techniques. DW-MRI and contrast enhanced (CE)-MRI are recommended to detect and characterise CRLM. Our main aim is to demonstrate the added value of DW-MRI, CE-MRI and CT scan to provide precise assessment of the viability of DLMs. In addition, we aim to improve prognostication and treatment strategies for CRLM patients using parenchymal sparing surgery (PSS). No large scale study has been conducted to date to determine the predictive value of DW-MRI combined with CE-MRI in confirming sites of DLMs and assessing their true status. This is the first collaborative study between EORTC, ESSO and JCOG with an integrated quality assurance (QA) program for imaging, surgery and pathology. Together, we also developed an infrastructure for surgical QA in clinical trials (SURCARE) to advance the surgical oncology research agenda in Europe and Asia.

Utility of Image Guidance in the Localization of Disappearing Colorectal Liver Metastases

BackgroundColorectal liver metastases that demonstrate a complete radiographic response during chemotherapy are increasingly common with advances in chemotherapy regimens and are described as disappearing liver metastases (DLMs). However, these DLMs often continue to harbor residual viable tumor. If these tumors are found in the operating room with ultrasound (US), they should be treated. The intraoperative sonographic visualization of these lesions, however, can be hindered by chemotherapy-associated liver parenchyma changes. The objective of this study was to evaluate the use of an intraoperative image guidance system, Explorer (Analogic Corporation, Peabody, MA), to aid surgeons in the identification of DLMs initially undetected by US alone. Study DesignIn a single-arm prospective trial, patients with colorectal liver metastases undergoing liver resection and/or ablation with one or more DLMs during neoadjuvant chemotherapy were enrolled. Intraoperatively, DLMs were localized with conventional US. Any DLM not found by conventional US was re-evaluated with the image guidance system. The primary outcome was the proportion of sonographically occult DLMs subsequently located by image-guided US. ResultsBetween April 2016 and November 2017, 25 patients with 61 DLMs were enrolled. Thirty-eight DLMs (62%) in 14 patients (56%) were not identified with US alone. Six (16%) DLMs in five patients (36%) were subsequently located with assistance of the image guidance system. The image guidance changed the intraoperative surgical plan in four of these patients. ConclusionsImage guidance can aid surgeons in the identification of initially sonographically occult DLMs and facilitate the complete surgical clearance of all sites of liver disease.

Clinical implications of disappearing colorectal liver metastases have changed in the era of hepatocyte-specific MRI and contrast-enhanced intraoperative ultrasonography

BackgroundClinical implication of disappearing liver metastases (DLMs) from colorectal cancer after chemotherapy needs to be reviewed in the era of modern imaging studies. MethodsBetween 2010 and 2015, 184 patients underwent curative hepatectomy for colorectal liver metastases following preoperative chemotherapy. The sites of metastases detected on pre-chemotherapy CE-CT were examined post-chemotherapy using CE-CT, gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging (EOB-MRI), and contrast-enhanced intraoperative ultrasonography (CE-IOUS). DLMs were defined as tumors that disappeared on CE-CT post chemotherapy. The detection rate of DLMs with EOB-MRI and CE-IOUS were assessed, and the outcome of DLMs resected and those left in place were reviewed. ResultsA total of 275 DLMs were noted in 59 patients. On EOB-MRI, 71 lesions (26%) were visible and were resected, 92% (65/71) of which contained viable disease. Using CE-IOUS, an additional 94 lesions were identified. A total of 165 DLMs (60%) were identified and resected by sequential use of EOB-MRI and CE-IOUS, 77% (127/165) of which contained viable disease. Of 110 DLMs not identified, 68 were resected, 4% (3/68) of which contained viable disease. Among 42 lesions left in place, 6 (14%) recurred during the median follow-up period of 27 (9–72) months. DiscussionEOB-MRI and CE-IOUS exploration identified clinically relevant DLMs containing viable disease with a high level of accuracy.

EORTC1527/JCOG1609INT: Diffusion-weighted MRI (DW-MRI) assessment of liver metastasis to improve surgical planning (DREAM).

TPS3633 Background: For patients with initially unresectable colorectal liver metastases (CRLM) with good clinical response to chemotherapy, the presence of disappearing liver metastases (DLMs) diagnosed by CT is a major independent prognostic factor. DW-MRI as well as contrast enhanced (CE)-MRI is recommended to detect and characterize CRLM. However, the correlation between radiological and pathological complete response has not been fully investigated using these latest imaging and pathology techniques. Our main aim is to demonstrate the added value of DW-MRI, CE-MRI to that of CT alone to provide precise assessment of the viability of DLMs. In addition, we aim to optimize the therapeutic management of CRLM patients. No prospective study has been conducted to determine the predictive value of DW-MRI combined with CE-MRI in confirming sites of DLMs and assessing their true status. Methods: This is the first collaborative study between EORTC, ESSO and JCOG with an integrated quality assurance program for imaging, surgery and pathology. Patients with unresectable CRLM will receive standard systemic chemotherapy and liver resection if resectable. Both CT and MRI (DW-MRI, CE-MRI and T1/T2) will be used to identify confirmed DLMs (cDLMs). cDLMs will be either resected or, if resection is not possible, followed-up without resection until 2 years after surgery to evaluate the true status of the cDLMs. The primary endpoint is negative predictive value (NPV) of DW-MRI, CE-MRI, T1/T2 and CT in confirming the status of cDLMs using as reference either the histopathological complete response or the absence of a local recurrence at the site of cDLMs during the follow up period of 2 years. The study aims at excluding a NPV≤0.85 and is powered under the alternative that the NPV≥0.95. The planned sample size is 92 evaluable (resected or left behind) cDLMs, with a 1-sided alpha of 5% and a power of 90% adjusting for within-patient correlation between cDLMs of 0.2 and an average number of 2 cDLMs per patient. Approximately 400 patients will be registered from European, Japanese and US sites over 3 years. As of February 2017, 2 patients have been enrolled. Clinical trial information: NCT02781935.

Disappearing Liver Metastases (DLM) from colorectal cancer – impact of intraoperative contrast-enhanced ultrasound

Disappearing Liver Metastases (DLM) from colorectal cancer – impact of intraoperative contrast-enhanced ultrasound

Disappearing liver metastases from colorectal cancer: impact of modern imaging modalities

BackgroundChemotherapy is often used before a resection for colorectal liver metastases. After chemotherapy, metastases may disappear on cross sectional imaging but residual metastatic disease may still exist. The aim of this retrospective study was to investigate the impact of new advancements in imaging technology such as magnetic resonance imaging (MRI) with liver specific contrast (Gd EOB DTPA) and contrast enhanced intra operative ultrasound (CE IOUS) on disappearing liver metastases (DLM). MethodsTwenty nine patients with one or more DLM undergoing surgical exploration were included. Pre operative imaging consisted of contrast enhanced multi detector computed tomography (MDCT) and/or MRI with liver specific contrast. At surgery, CE IOUS was used when tumours known from pre chemotherapy imaging were not found by inspection or intra operative ultrasound. ResultsPatients presented 66 DLM. At surgical exploration, 42 DLM were identified and treated (64%). CE IOUS detected one additional DLM not found by intra operative ultrasound. For metastases ≤10 mm on histological analysis, imaging sensitivities for MRI and MDCT before surgery but after chemotherapy were 26/49 (53%) and 24/66 (36%), respectively. ConclusionA majority of DLM are identified during surgery using intra operative ultrasound, with only little additional value of CE IOUS. The sensitivities of post chemotherapy imaging modalities for small metastases are low in the setting of DLM. For surgical planning, an optimized pre chemotherapy imaging is essential.

Hepatic Resection for Disappearing Liver Metastasis: a Cost-Utility Analysis

BackgroundWe sought to estimate the cost-effectiveness of hepatic resection (HR) (strategy A) relative to surveillance plus 6 months of additional systemic chemotherapy (sCT) (strategy B) for patients with colorectal disappearing liver metastases (DLM). MethodsA Markov model was developed using data from a systematic literature review. Three base cases were evaluated: (1) a 60-year-old patient with three lesions in the right hemi-liver who underwent 6 months of sCT, had normalized carcinoembryonic antigen (CEA), and was diagnosed with DLM through a computed tomography (CT) scan; (2) a 60-year-old patient with three lesions in the right hemi-liver who underwent 6 months of sCT, had normalized CEA, and was diagnosed with DLM through a magnetic resonance imaging (MRI) scan; and (3) a 60-year-old patient with three lesions in the right hemi-liver who underwent 6 months of sCT plus hepatic artery infusion (HAI), had normalized CEA, and was diagnosed with DLM through a MRI scan. The outcomes evaluated were quality-adjusted life months (QALMs), incremental cost-effectiveness ratio (ICER), and net health benefit (NHB). ResultsThe NHB of strategy A versus strategy B was positive in base case 1 (7.7 QALMs, ICER $34.449/quality-adjusted life year (QALY)) and base case 2 (1.6 QALMs, ICER $43,948/QALY). In contrast it was negative (−0.2 QALMs, ICER $72,474/QALY) for base case 3. Monte Carlo simulation showed that strategy B is acceptable only in old patients (>60 years) with normalized CEA and MRI-based diagnosis. In younger patients, strategy B may reach cost-effectiveness only after sCT plus HAI. ConclusionSurveillance of DLM after sCT was more beneficial and cost-effective among patients >60 years with multiple factors predictive of true complete pathological response, such as normalization of CEA, HAI therapy, BMI ≤30 kg/m2, and diagnosis of DLM made through MRI.

Selection of Patients with Colorectal/Liver Metastases for Surgical Intervention: Current Issues and Challenges

Resection of colorectal liver metastases (CRLM) represents the best chance for cure, but appropriate selection of patients can present challenging clinical scenarios. The PubMed database was searched for articles relevant to CRLM published between 1990 and December 2013. The ability to safely achieve curative resection depends heavily on the adequacy of the future liver remnant (FLR). The FLR volume can be improved through several techniques including portal vein embolization and surgical portal vein ligation with in situ liver split (ALPPS). Disappearing liver metastases (DLM) may develop as a result of robust response to chemotherapy. Concordance between radiographic DLM and true pathologic response is poor and up to 85 % of DLM that undergo resection will demonstrate viable tumor on pathological examination. The rate of true pathologic response for lesions treated with hepatic artery infusion may be higher. Modern chemotherapeutics and techniques to improve the FLR have increased the number of patients who are candidates for potentially curative resection. In cases of DLM, curative resection should aim to include all sites of disease present prior to systemic chemotherapy if possible.

Managing Disappearing Liver Metastases Following Chemotherapy

Liver metastases that can no longer be identified on radiographic images after chemotherapy are termed disappearing metastases. This most commonly occurs in patients with multifocal bilobar metastases of differing size who are extensively treated with chemotherapy. The most effective treatment for disappearing liver metastases is prevention, through the use of high-quality pretreatment imaging, early involvement of a liver surgeon, and limitation of neoadjuvant chemotherapy to as few cycles as are needed for the metastases to become resectable. If a treated metastasis cannot be identified on CT, then MRI should be used to confirm a true disappearance. As the disappearance of a metastasis does not necessarily signify a pathologic complete response at that site, when possible, resection of liver metastases should include all sites that initially contained disease. If this is not possible, then these patients can be considered for other local therapies and should be followed closely for disease recurrence.

Usefulness of Contrast-Enhanced Intraoperative Ultrasound in Identifying Disappearing Liver Metastases from Colorectal Carcinoma After Chemotherapy

Preoperative chemotherapy sometimes makes colorectal liver metastases disappear or diminish. Contrast-enhanced intraoperative ultrasound (CE-IOUS) using perflubutane may identify such metastases. Among 131 consecutive patients who underwent hepatic resection, 86 had received preoperative chemotherapy. Of these patients, 72 were examined using contrast-enhanced computed tomography (CE-CT), gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging (EOB-MRI), contrast-enhanced ultrasound (CEUS), intraoperative ultrasound (IOUS), and CE-IOUS; these patients were the subject of the present study. Effects of IOUS and CE-IOUS to search for disappearing liver metastases (DLM) and tumors with a diameter of 1 cm or less based on the preoperative imaging were assessed. A total of 32 DLMs were noted in 11 patients. Four DLMs were identified using IOUS, and 16 DLMs (including the four DLMs identified using IOUS) were identified using CE-IOUS. Of the 16 DLMs that were missed using both IOUS and CE-IOUS, nine were resected using anatomical resection and seven were not resected. One of the nine resected DLMs was histologically proven to be adenocarcinoma. Three of the seven unresected DLMs showed tumor regrowth during a postoperative follow-up examination. CE-IOUS identified 79 % of the 19 DLMs that were ultimately confirmed as liver metastases, whereas IOUS identified 21 % of them (p < 0.004). Among the 202 tumors that were identified using preoperative imaging, 54 were 1 cm or less in diameter. The sensitivity of CE-IOUS for these tumors were superior to CE-CT (p < 0.04) and IOUS (p < 0.04), respectively. CE-IOUS might be necessary after preoperative chemotherapy for colorectal liver metastasis.

AUGIS trainee prize winner: Antimicrobial prophylaxis prior to pancreatico-duodenectomy

AUGIS trainee prize winner: Antimicrobial prophylaxis prior to pancreatico-duodenectomy

Disappearing Colorectal Liver Metastases after Chemotherapy: Should we be Concerned?

BackgroundWith increasing efficacy of preoperative chemotherapy for colorectal cancer, more patients will present with one or more disappearing liver metastases (DLM) on preoperative cross-sectional imaging. Patients and MethodsA retrospective review was conducted evaluating the radiological response to preoperative chemotherapy for 168 patients undergoing surgical therapy for colorectal liver metastases at Johns Hopkins Hospital between 2000 and 2008. ResultsForty patients (23.8%) had one or more DLM, accounting for a total of 127 lesions. In 22 patients (55%), all DLM sites were treated during surgery. Of the 17 patients with unidentified, untreated DLM, ten patients (59%) developed a local recurrence at the initial site, half of which also developed recurrences in other sites. While the intrahepatic recurrence rate was higher for patients with DLM left in situ (p = 0.04), the 1-, 3-, and 5-year overall survival rate was not significantly different for patients with DLM left in situ (93.8%, 63.5%, and 63.5%, respectively) when compared to patients with a radiological chemotherapy response in whom all original disease sites were surgically treated (92.3%, 70.8%, and 46.2%, respectively; p = 0.66). ConclusionsDLM were frequently observed in patients undergoing preoperative chemotherapy for liver metastases. Survival was comparable in patients with untreated DLM, in spite of high intrahepatic recurrence rates seen in these patients. Therefore, aggressive surgical therapy should be considered in patients with marked response to chemotherapy, even when all DLM sites cannot be identified.