• Humans
• Liver Transplantation/adverse effects
• Liver Neoplasms/surgery
• Hepatectomy
• Abdomen

• metastatic colorectal cancer
• stage IV colon cancer
• stage IV rectal cancer
• treatment of stage IV colorectal cancer

• liver resection
• parenchyma-sparing liver resection
• regenerative liver surgery
• therapeutic options in liver surgery

• Humans
• Hepatectomy/methods
• Quality of Life
• Liver Regeneration
• Liver/surgery
• Liver/pathology
• Portal Vein/surgery
• Treatment Outcome

Surgical resection for colorectal liver metastases (CRLM) may offer the best opportunity to improve prognosis. However, only about 20% of CRLM cases are indicated for resection at the time of diagnosis (initially resectable), and the remaining cases are treated as unresectable (initially unresectable). Thanks to recent remarkable developments in chemotherapy, interventional radiology, and surgical techniques, the resectability of CRLM is expanding. However, some metastases are technically resectable but oncologically questionable for upfront surgery. In pancreatic cancer, such cases are categorized as “borderline resectable”, and their definition and treatment strategies are explicit. However, in CRLM, although various poor prognosis factors have been identified in previous reports, no clear definition or treatment strategy for borderline resectable has yet been established. Since the efficacy of hepatectomy for CRLM was reported in the 1970s, multidisciplinary treatment for unresectable cases has improved resectability and prognosis, and clarifying the definition and treatment strategy of borderline resectable CRLM should yield further improvement in prognosis. This review outlines the present status and the future perspective for borderline resectable CRLM, based on previous studies.

• Borderline resectable
• Colorectal liver metastases
• Adjuvant chemotherapy
• Hepatectomy
• Colorectal cancer

Liver metastasis is a major therapeutic challenge and common cause of death for patients with colorectal cancer. While systemic treatment especially chemotherapy remains the mainstay of treatment, selected patients with liver-only metastasis may further benefit from liver-directed therapies. Direct infusion of chemotherapy into the liver metastases via an implantable hepatic arterial infusion pump (HAIP) is potentially an effective way to improve treatment response and survival in selected patients. Here, we reviewed the literature utilizing HAIP as a liver-directed modality alone and in combination with systemic chemotherapy. We discussed two cases who were successfully treated with this combinatorial approach and achieved remission or prolongation of disease control. We discussed the limitations, toxicities of combined systemic and HAIP modalities. Lastly, we provided insights on the use of HAIP in the modern era of systemic treatment for colorectal cancer patients with liver metastasis.

Colorectal cancer (CRC) is the third most prevalent malignancy and the second most common cause of death in the US. Liver is the most common site of colorectal metastases. About 13% of patients with colorectal cancer have liver metastasis on initial presentation and 50% develop them during the disease course. Although systemic chemotherapy and immunotherapy are the mainstay treatment for patients with metastatic disease, for selected patients with predominant liver metastasis, liver-directed approaches may provide prolonged disease control when combined with systemic treatments. Hepatic artery infusion pump (HAIP) chemotherapy is an approach which allows direct infusion of chemotherapeutic into the liver and is especially useful in the setting of multifocal liver metastases. When combined with systemic chemotherapy, HAIP improves the response rate, provides more durable disease control, and in some patients leads to successful resection. To ensure safety, use of HAIP requires multidisciplinary collaboration between interventional radiologists, medical oncologists, hepatobiliary surgeons and treatment nurses. Here, we review the benefits and potential risks with this approach and provide our single institution experience on two CRC patients successfully treated with HAIP in combination with systemic chemotherapy. We provide our recommendations in adopting this technique in the current era for patient with colorectal liver metastases.

• FUDR
• HAIP
• colorectal cancer
• liver metastasis

Two-stage hepatectomy (TSH) is a well-established surgical technique, used to treat bilateral colorectal liver metastases (CRLM) with a small future liver remnant (FLR). However, in classical TSH, drop-out is reported to be around 25%-40%, due to insufficient FLR increase or progression of disease. Trans-arterial radioembolization (TARE) has been described to control locally tumor growth of liver malignancies such as hepatocellular carcinoma, but it has been also reported to induce a certain degree of contralateral liver hypertrophy, even if at a lower rate compared to portal vein embolization or ligation.

Herein we report the case of a 75-year-old female patient, where TSH and TARE were combined to treat bilateral CRLM. According to computed tomography (CT)-scan, the patient had a hepatic lesion in segment VI-VII and two other confluent lesions in segment II-III. Therefore, one-stage posterior right sectionectomy plus left lateral sectionectomy (LLS) was planned. The liver volumetry estimated a FLR of 38% (segments I-IV-V-VIII). However, due to a more than initially planned, extended right resection, simultaneous LLS was not performed and the patient underwent selective TARE to segments II-III after the first surgery. The CT-scan performed after TARE showed a reduction of the treated lesion and a FLR increase of 55%. Carcinoembryonic antigen and CA 19.9 decreased significantly. Nearly three months later after the first surgery, LLS was performed and the patient was discharged without any postoperative complications.

According to this specific experience, TARE was used to induce liver hypertrophy and simultaneously control cancer progression in TSH settings for bilateral CRLM.

• Trans-arterial
• Radioembolization
• Two-stage hepatectomy
• Colorectal liver metastases
• Selective internal radiation therapy
• Yttrium90
• Case report

Liver metastasis is the most common form of distant metastasis in colorectal cancer and is a key factor for prognosis in patients with colorectal cancer. Surgery may be the only way to cure colorectal liver metastases. This paper mainly summarizes the latest progress in surgical treatment of colorectal liver metastases, including how to increase resection rate of liver metastases with neoadjuvant therapy or staged hepatectomy, the effect of surgical margin on the prognosis of patients, the timing of surgery in patients with synchronous colorectal liver metastasis, the impact of laparoscopic hepatectomy of liver metastases, the application of liver transplantation in patients with colorectal liver metastases, etc, with an aim to help develop an optimal treatment for patients with colorectal liver metastases through combination of surgical innovations with individualized treatment, thereby improving patients' disease-free survival and overall survival.

• Colorectal liver metastasis
• Surgery
• Prognosis

• Liver partition
• future liver remnant (FLR)
• hepatectomy
• liver cancer
• portal ligation
• post-hepatectomy liver failure (PHLF)

• Combination therapy
• Hepatic metastases
• Hepatic resection
• MR-guided intervention
• Microwave ablation
• Percutaneous thermoablation
• Radiofrequency ablation

• Colorectal liver metastasis
• Hepatectomy
• Liver resection
• Neoadjuvant chemotherapy
• Synchronous metastasis

• Colorectal liver metastases
• Comprehensive therapy
• Diagnosis
• Multidisciplinary team

• colorectal liver metastases
• liver resection
• right hepatic trisectionectomy

• colorectal liver metastases
• liver resection
• liver surgery
• radiofrequency ablation
• systematic review

The aim of the study was to evaluate if associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) could increase resection rates (RRs) compared with two-stage hepatectomy (TSH) in a randomized controlled trial (RCT).

Radical liver metastasis resection offers the only chance of a cure for patients with metastatic colorectal cancer. Patients with colorectal liver metastasis (CRLM) and an insufficient future liver remnant (FLR) volume are traditionally treated with chemotherapy with portal vein embolization or ligation followed by hepatectomy (TSH). This treatment sometimes fails due to insufficient liver growth or tumor progression.

A prospective, multicenter RCT was conducted between June 2014 and August 2016. It included 97 patients with CRLM and a standardized FLR (sFLR) of less than 30%. Primary outcome—RRs were measured as the percentages of patients completing both stages of the treatment. Secondary outcomes were complications, radicality, and 90-day mortality measured from the final intervention.

Baseline characteristics, besides body mass index, did not differ between the groups. The RR was 92% [95% confidence interval (CI) 84%–100%] (44/48) in the ALPPS arm compared with 57% (95% CI 43%–72%) (28/49) in the TSH arm [rate ratio 8.25 (95% CI 2.6–26.6); P < 0.0001]. No differences in complications (Clavien–Dindo ≥3a) [43% (19/44) vs 43% (12/28)] [1.01 (95% CI 0.4–2.6); P = 0.99], 90-day mortality [8.3% (4/48) vs 6.1% (3/49)] [1.39 [95% CI 0.3–6.6]; P = 0.68] or R0 RRs [77% (34/44) vs 57% (16/28)] [2.55 [95% CI 0.9–7.1]; P = 0.11)] were observed. Of the patients in the TSH arm that failed to reach an sFLR of 30%, 12 were successfully treated with ALPPS.

ALPPS is superior to TSH in terms of RR, with comparable surgical margins, complications, and short-term mortality.

Colorectal cancer is the third most common cancer in men and the second most common in women worldwide. Almost a third of the patients has or will develop liver metastases. Neoadjuvant chemotherapy (NAC) has recently become nearly systematic prior to surgery of colorectal livers metastases (CRLMs). The response to NAC is evaluated by radiological imaging according to morphological criteria. More recently, the response to NAC has been evaluated based on histological criteria of the resected specimen. The most often used score is the tumor regression grade (TRG), which considers the necrosis, fibrosis, and number of viable tumor cells.

To analyze the predictive factors of the histological response, according to the TRG, on CRLM surgery performed after NAC.

From January 2006 to December 2013, 150 patients who had underwent surgery for CRLMs after NAC were included. The patients were separated into two groups based on their histological response, according to Rubbia-Brandt TRG. Based on their TRG, each patient was either assigned to the responder (R) group (TRG 1, 2, and 3) or to the non-responder (NR) group (TRG 4 and 5). All of the histology slides were re-evaluated in a blind manner by the same specialized pathologist. Univariate and multivariate analyses were performed.

Seventy-four patients were classified as responders and 76 as non-responders. The postoperative mortality rate was 0.7%, with a complication rate of 38%. Multivariate analysis identified five predictive factors of histological response. Three were predictive of non-response: More than seven NAC sessions, the absence of a radiological response after NAC, and a repeat hepatectomy (P < 0.005). Two were predictive of a good response: A rectal origin of the primary tumor and a liver-first strategy (P < 0.005). The overall survival was 57% at 3 yr and 36% at 5 yr. The disease-free survival rates were 14% at 3 yr and 11% at 5 yr. The factors contributing to a poor prognosis for disease-free survival were: No histological response after NAC, largest metastasis > 3 cm, more than three preoperative metastases, R1 resection, and the use of a targeted therapy with NAC (P < 0.005).

A non-radiological response and a number of NAC sessions > 7 are the two most pertinent predictive factors of non-histological response (TRG 4 or 5).

• Colorectal liver metastasis
• Tumor regression grade
• Neoadjuvant chemotherapy
• Liver surgery
• Histological response
• Hepatectomy

• Colon cancer
• Liver metastases
• Microwave ablation
• Radiofrequence ablation
• Surgery

• Ablation Techniques
• Colectomy
• Colorectal Neoplasms/pathology
• Colorectal Neoplasms/surgery
• Combined Modality Therapy
• Disease Progression
• Humans
• Metastasectomy
• Neoplasm Staging

Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) is a recently introduced technique aimed to perform two-stage hepatectomy in patients with a variety of primary or secondary neoplastic lesions. ALPSS is based on a preliminary liver resection associated with ligation of the portal branch directed to the diseased hemiliver (DH), followed by hepatectomy after an interval of time in which the future liver remnant (FLR) hypertrophied adequately (partly because of preserved arterialization of the DH). Multidetector computed tomography (MDCT) and magnetic resonance imaging (MRI) play a pivotal role in patients’ selection and FLR assessment before and after the procedure, as well as in monitoring early and late complications, as we aim to review in this paper. Moreover, we illustrate main abdominal MDCT and MRI findings related to ALPPS.

• Hepatectomy
• Computed tomography
• Magnetic resonance imaging
• Associating liver partition and portal vein ligation for staged hepatectomy
• Liver surgery

• colorectal liver metastasis
• cure
• extrahepatic disease
• hepatectomy
• predictive model

There is discrepancy and failure to adhere to current international guidelines for the management of metastatic colorectal cancer (CRC) in hospitals in Greece and Cyprus. The aim of the present document is to provide a consensus on the multidisciplinary management of metastastic CRC, considering both special characteristics of our Healthcare System and international guidelines. Following discussion and online communication among the members of an executive team chosen by the Hellenic Society of Medical Oncology (HeSMO), a consensus for metastastic CRC disease was developed. Statements were subjected to the Delphi methodology on two voting rounds by invited multidisciplinary international experts on CRC. Statements reaching level of agreement by ≥80% were considered as having achieved large consensus, whereas statements reaching 60-80% moderate consensus. One hundred and nine statements were developed. Ninety experts voted for those statements. The median rate of abstain per statement was 18.5% (range: 0-54%). In the end of the process, all statements achieved a large consensus. The importance of centralization, care by a multidisciplinary team, adherence to guidelines, and personalization is emphasized. R0 resection is the only intervention that may offer substantial improvement in the oncological outcomes.

• Colorectal cancer
• guidelines
• metastatic disease
• surgery

• Colorectal liver metastasis
• Early recurrence
• Hepatectomy
• Minimum p value approach
• Salvage surgery

• Adult
• Aged
• Aged, 80 and over
• Colorectal Neoplasms/pathology
• Female
• Hepatectomy
• Humans
• Liver Neoplasms/mortality
• Liver Neoplasms/secondary
• Liver Neoplasms/surgery
• Male
• Middle Aged
• Neoplasm Recurrence, Local/etiology
• Prognosis
• Salvage Therapy

• Colorectal neoplasms
• Hepatectomy
• Liver
• Radiofrequency catheter ablation

Hepatic metastasectomy for patients with primary colorectal cancer offers better long-term outcome, and chemotherapy can increase the rate of hepatic resectability for patients with initially inoperable disease. The pattern of liver metastasis and status of the primary tumor are rarely discussed in the analysis of long-term outcome. In this report, we evaluate the influence of the pattern of metastasis on clinical features and prognosis.

One hundred and fifty-nine patients who underwent hepatic metastasectomy with curative intent for liver metastasis of colorectal cancer between October 1991 and December 2006 were enrolled. Patients were grouped according to whether liver metastasis was centrally or peripherally located, based on imaging and operative findings. Patient demographics, characteristics of the primary and metastatic tumors, and surgical outcomes were analyzed for long-term survival.

A greater proportion of patients with centrally located metastases were male, as compared with those with peripherally located metastases. Compared with patients with peripherally located metastases, patients with centrally located metastases were more likely to have multiple lesions (P = 0.016), involvement of multiple segments (P = 0.006), large metastases (P < 0.001), and bilobar distribution of metastases (P < 0.001). The estimated 5-year recurrence-free and overall survival rates were 22.4% and 34.2%, respectively. Univariate analysis revealed that centrally located metastasis, primary tumor in the transverse colon, metastasis in regional lymph nodes, initial extrahepatic metastasis, synchronous liver metastasis, multiple lesions, poorly differentiated tumor, and resection margin <10 mm were significant poor prognostic factors for recurrence-free survival and overall survival. Cox regression analysis showed that inadequate resection margin and centrally located liver metastasis were significant predictors of shorter overall survival.

In colorectal cancer, centrally located liver metastasis represents a poor prognostic factor after hepatectomy, and is associated with early recurrence. Neoadjuvant chemotherapy may be used to downstage centrally located liver metastases to improve outcome.

• Hepatectomy
• Liver dysfunction
• Liver insufficiency
• Morbidity
• Mortality

• Colorectal cancer (CRC)
• hepatectomy
• liver metastases
• portal vein embolization (PVE)
• radiofrequency ablation (RFA)

• CRC
• Chemoradiation
• Chemotherapy
• Colorectal cancer
• Hepatectomy
• Lymphadenopathy
• Metastases
• Synchronous liver metastasis
• sCRLM

• Associating liver partition and portal vein ligation for staged hepatectomy
• Future liver remnant
• Liver failure
• Liver hypertrophy
• Portal vein embolization

• Colorectal cancer (CRC)
• hepatectomy
• liver resection
• metastasectomy
• metastatic colorectal cancer (mCRC)
• surgical management, survival