Resection of liver metastases from colorectal cancer

PURPOSE: This study was undertaken to determine the indications for and value of liver resection for metastases from colorectal cancer. METHODS: From 1978 through 1991, 66 patients were operated on for liver metastases from colorectal cancer. All patients had had a curative resection of their colorectal cancer. Forty resections of the liver were major anatomic resections. RESULTS: Five patients died in the postoperative period. All resections were intended to be curative, but in 16 of the patients the resection became noncurative. None of these patients lived more than two years after liver resection. Fifty patients with a curative resection had a three-year survival rate of 36 percent, postoperative death included. Recurrence in the liver was observed in 30 patients (60 percent) from 3 to 33 (median, 11) months after the liver resection. Four patients had repeated resections performed. Two of them are alive without recurrences 34 and 60 months after the first liver resection, respectively. The difference in survival between curative and noncurative liver resection was highly significant (P=0.01). CONCLUSIONS: Sex, age, Dukes stage of primary colorectal cancer, synchronous or metachronous appearance of metastases, or number of metastases could not predict long-term prognosis. The only factors of predictive value were tumor size less than 4 cm in diameter, a free resection margin, and no extrahepatic tumor. If it is possible to do a curative resection, there should be few contraindications against liver surgery as it is the only treatment that can demonstrate long-term survival for approximately one-third of the patients, and it is the only possibility of a cure.     

Colorectal peritoneal metastases: Optimal management review

The peritoneum is a common site of dissemination for colorrectal cancer, with a poorer prognosis than other sites of metastases. In the last two decades, it has been considered as a locoregional disease progression and treated as such with curative intention treatments. Cytoreductive surgery(CRS) and hyperthermic intraperitoneal chemotherapy(HIPEC) is the actual reference treatment for these patients as better survival results have been reached as compared to systemic chemotherapy alone, but its therapeutic efficacy is still under debate. Actual guidelines recommend that the management of colorectal cancer with peritoneal metastases should be led by a multidisciplinary team carried out in experienced centers and consider CRS + HIPEC for selected patients. Accumulative evidence in the last three years suggests that this is a curative treatment that may improve patients disease-free survival, decrease the risk of recurrence, and does not increase the risk of treatment-related mortality. In this review we aim to gather the latest results from referral centers and opinions from experts about the effectiveness and feasibility of CRS + HIPEC for treating peritoneal disease from colorectal malignancies.     

Treatment of liver metastases with moderate peritoneal carcinomatosis by hepatectomy and cytoreductive surgery followed by immediate post-operative intraperitoneal chemotherapy: feasibility and preliminary results

BACKGROUND/AIMS: Peritoneal carcinomatosis (PC) discovered during hepatectomy is usually a contraindication to resection. A potentially efficient treatment of PC is the resection of the macroscopic disease and the treatment of the residual microscopic disease with immediate post-operative intraperitoneal chemotherapy (IPIC) (before the entrapment of cancer cells inside the fibrin deposit which rapidly cover the injured tissues). Feasibility and survival results of this treatment, combined with major hepatectomy, have never been evaluated. The purpose of this study is to report tolerance and preliminary results in patients with liver metastases synchronous to moderate PC, treated with hepatectomy, complete cytoreductive surgery, and IPIC. METHODOLOGY: Twelve patients with liver metastases and moderate PC from miscellaneous origins, underwent: 1) hepatectomy (9 of them were major hepatectomies); 2) complete cytoreductive surgery of the PC resecting between 20 and 150 nodules; and, 3) IPIC, for 5 days, according to histology. RESULTS: There was no mortality. Morbidity was mainly due to four transient biliary leakages (33%) and there was no systemic complication due to the chemotherapy. After a median follow-up of 14.4 months, there was no detectable recurrence of the PC. Preliminary results concerning survival are promising with 7 patients without recurrent disease. CONCLUSIONS: When a minimal or moderate PC is discovered during laparotomy for liver resection of metastases, the combination of hepatectomy with complete cytoreductive surgery of the peritoneal disease, followed with IPIC is logical and feasible. This aggressive treatment is well tolerated although the frequency of biliary leakage seems to be higher than that after standard hepatectomy. No recurrence of the peritoneal disease was detected and survival results are very promising.     

Neoadjuvant and adjuvant therapy in relation to surgery for colorectal liver metastases

Liver resection is associated with prolonged survival in patients with colorectal liver metastases. At diagnosis, 15-20% of patients have resectable colorectal liver metastases whereas other patients have too advanced disease to enable surgical treatment and receive chemotherapy. In patients undergoing resection of colorectal liver metastases, disease relapse occurs in up to 70%. Therefore, a combined approach including preoperative or postoperative chemotherapy or both has been tested to improve outcome after surgery. In patients with unresectable colorectal liver metastases, chemotherapy is initially the sole treatment option. The considerable improvement of the efficacy of anticancer agents has contributed to increase the response rate in patients with advanced colorectal cancer. In case of major response to chemotherapy, surgery with curative intent can be offered to patients with initially unresectable liver metastases.     

Cytoreductive surgery and intraperitoneal chemotherapy for colorectal peritoneal metastases

AIM: To systematically review the available evidence regarding cytoreductive surgery (CRS) and intraperitoneal chemotherapy (IPC) for colorectal peritoneal metastases (CPM).METHODS: An electronic literature search was carried out to identify publications reporting oncological outcome data (overall survival and/or disease free survival and/or recurrence rates) following CRS and IPC for treatment of CPM. Studies reporting outcomes following CRS and IPC for cancer subtypes other than colorectal were only included if data were reported independently for colorectal cancer-associated cases; in addition studies reporting outcomes for peritoneal carcinomatosis of appendiceal origin were excluded.RESULTS: Twenty seven studies, published between 1999 and 2013 with a combined population of 2838 patients met the predefined inclusion criteria. Included studies comprised 21 case series, 5 case-control studies and 1 randomised controlled trial. Four studies provided comparative oncological outcome data for patients undergoing CRS in combination with IPC vs systemic chemotherapy alone. The primary indication for treatment was CPM in 96% of cases (2714/2838) and recurrent CPM (rCPM) in the remaining 4% (124/2838). In the majority of included studies (20/27) CRS was combined with hyperthermic intraperitoneal chemotherapy (HIPEC). In 3 studies HIPEC was used in combination with early post-operative intraperitoneal chemotherapy (EPIC), and 2 studies used EPIC only, following CRS. Two studies evaluated comparative outcomes with CRS + HIPEC vs CRS + EPIC for treatment of CPM. The delivery of IPC was performed using an “open” or “closed” abdomen approach in the included studies.CONCLUSION: The available evidence presented in this review indicates that enhanced survival times can be achieved for CPM after combined treatment with CRS and IPC.     

Resection and local therapy for liver metastases

In 30-50% of patients the liver is a preferred site of distant disease for many malignant tumours. Due to the high incidence, most of the available data relate to metastases arising from colorectal primaries. Surgical resection is at present the only treatment offering potential cure. The achievable 5-year survival rate is 30%. However, only 10-15% of patients with colorectal liver metastases can undergo potentially curative liver resection. Therefore, accurate staging is an important prerequisite in selecting patients who would benefit from surgery. Recurrence of hepatic metastases after potentially curative resection occurs in up to 60% of the cases. Results demonstrate that re-resection of liver metastases can provide long-term survival rates in a carefully selected group of patients without extrahepatic disease. Because of the high rate of recurrences following an apparently curative resection several authors investigated the use of adjuvant chemotherapy (systemic, intraportal, and hepatic arterial infusion). Until recently none had shown effectiveness. Pre-operative chemotherapy seems to be a promising approach in patients with liver metastases initially considered unsuitable for radical surgery. Recently, neoadjuvant chemotherapy has been proposed as an alternative approach to conventional surgery as initial management with the aim of improving the results in resectable liver metastases. Interventional strategies (ethanol injection, cryosurgery, laser-induced thermotherapy, radio-frequency ablation) and combined modalities (surgical/interventional) are additive methods which may help to improve treatment results in the future.     

腹膜转移的结肠癌患者MDT诊治二例

本文描述了2例异时性腹膜转移的结肠癌病例的多学科诊治过程。1例多发转移,1例单发转移。这两例患者经MDT讨论后都首先采用了肿瘤减灭术联合腹腔热灌注化疗的治疗模式（cytoreductive surgery,CRS/hyperthermic intraperitoneal peroperative chemotherapy,HIPEC）,单发转移的患者目前获得了12个月的无病生存期（disease-free survival,DFS）,而多发转移的患者也获得了12个多月的总生存期（overall survival,OS）。目前发现与结直肠癌腹膜转移患者OS相关的因素包括肿瘤减灭术（CRS）完全程度和肿瘤累及的范围（腹膜转移癌指数）等。因此,对于结直肠癌的腹膜转移患者,评估病变范围极其重要,对于较局限的腹膜转移,多学科的综合诊治和积极的治疗手段能改善这部分患者的生存时间和生存质量。     

Combined portal vein embolization and preoperative chemotherapy prior to liver resection for colorectal cancer metastases

Abstract

Objective. Compare perioperative course and long-term mortality after liver resection for colorectal cancer (CRC) metastases between patients who had preoperative treatment with portal vein embolization (PVE) and chemotherapy or chemotherapy alone. Methods. Among patients undergoing liver resection for CRC metastases following preoperative chemotherapy treatment, 17 patients who had received preoperative PVE (group A) were compared with 17 matched controls who had no PVE (group B). Perioperative course and long-term mortality were compared between groups A and B and between group A and the entire group of 75 cases with preoperative chemotherapy (group C). Results. Baseline characteristics for the matched groups A and B were similar. Group C included less major resections. Median intraoperative bleeding was 1600 ml in group A, 1200 ml in group B, and 1000 ml in group C (p < 0.05 vs. group A). Median postoperative stay was comparable in all groups (8–9 days). Operation time was 542 min in group A and 464 min in group B (p < 0.01). Mortality after 30 days and 1, 2, and 5 years was similar in all groups. Conclusion. Perioperative outcome and long-term survival did not differ when comparing liver resection for CRC liver metastases preceded by PVE and chemotherapy or chemotherapy alone, except for the operation time. The study supports the safety of this “aggressive” combination approach in patients in need of tumor “downstaging” by chemotherapy and PVE to increase the remnant liver volume.     

Clinical outcome after biliary drainage for metastatic colorectal cancer: Survival analysis and prognostic factors

IntroductionBiliary obstruction secondary to colorectal cancer liver metastases is associated with a poor prognosis especially when chemotherapy cannot be re-started. The aim of this study was to determine the survival after biliary drainage and the associated prognostic factors.MethodsPatients from two French centers were included retrospectively after first biliary endoscopic retrograde cholangiopancreatography or percutaneous transhepatic cholangiography drainage for biliary obstruction secondary to liver metastases of colorectal cancer, occurring during chemotherapy.ResultsThe final analysis included 69 patients. Overall median survival was 115 days. In univariate analysis, a previous liver surgery, technical and functional success of drainage and restarted chemotherapy were significantly associated with an improved survival. Chemotherapy was restarted after a median of 27 days. When drainage was efficient, survival improved from 33 to 262 days (p < 0.001). In multivariate analysis, significant protective factors for survival included previous a hepatectomy (HR 0.41) and functional success of the drainage (HR 0.29). Predictive factors for death included increased lines of chemotherapy (HR 1.68) and fever before drainage (HR 2.97).ConclusionsThis is the first study concerning the benefits of biliary drainage for malignant biliary obstruction during the course of chemotherapy for colorectal cancer. A successful biliary drainage leads to improved survival and allows achievement of chemotherapy for 70% of patients.     

Management of peritoneal carcinomatosis from colorectal cancer: review of the literature

Background

Today, we do not have a universally accepted evidence on how to treat peritoneal carcinomatosis (PC) from colorectal cancer (CRC) in international guidelines.

Methods

The present study is a review of the literature investigating current strategies to treat CRC PC.

Results

Despite the progresses of systemic chemotherapy, the presence of PC among patients with metastatic CRC reduces the overall survival to 30 %, and only 4 % of patients with PC from CRC treated are alive for 5 years. Many trials evaluate the combined treatment of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for CRC PC, suggesting a survival benefit in highly selected patients. Only one trial is randomized and presents some biases. The two main prognostic factors are Peritoneal Cancer Index (PCI) and completeness of cytoreduction score (CC score). There is no universal agreement on how to approach the synchronous presence of PC and liver metastasis with a curative intent during the same procedure. A growing interest among the scientific community has arisen about systematic second-look surgery and HIPEC treatment in high-risk patients.

Conclusion

Current evidences suggest that CRS and HIPEC might be beneficial in highly selected patients affected with PC from CRC. Anyway, today, there is a shortage of well-designed phase 3 trials.     

The role of surgery in the treatment of liver metastases for colorectal cancer patients.

BACKGROUND/AIMS: Liver metastases deriving from colorectal cancer can be treated with curative intention in a select number of patients. Controversy does, however, persist pertaining to the impact of adjuvant treatment strategies. The aim of this study is to elucidate upon the various treatment modalities for patients suffering from liver metastases of colorectal primary tumor as well as to provide a rationale for surgical and adjuvant treatment. METHODOLOGY: From November 1987 to September 1998, a total of 449 consecutive patients suffering from liver metastases deriving from a colorectal cancer were documented at our institution in a prolective study. Prognostic factors providing the most beneficial outcome (whether with surgical and/or adjuvant treatment modalities) were analyzed by univariate and multivariate analysis. RESULTS: Whenever possible, curative (R0) surgical resection of colorectal liver metastases provides the most benefit to the patient. Multivariate analysis revealed tumor infiltration of the lymph nodes of the hepatoduodenal ligament and metachronous occurrence of liver metastases as most independent factors related to survival. CONCLUSIONS: Adjuvant post-operative chemotherapy fails to significantly improve survival following resection of liver metastases when compared to the liver resection only group. In patients with unresectable metastases, regional arterial chemotherapy did not improve survival significantly when compared with systemic chemotherapy.     

Peritoneal carcinomatosis

Several gastrointestinal and gynecological malignancies have the potential to disseminate and grow in the peritoneal cavity.The occurrence of peritoneal carcinomatosis(PC)has been shown to significantly decrease overall survival in patients with liver and/or extraperitoneal metastases from gastrointestinal cancer.During the last three decades,the understanding of the biology and pathways of dissemination of tumors with intraperitoneal spread,and the understanding of the protective function of the peritoneal barrier against tumoral seeding,has prompted the concept that PC is a loco-regional disease:in absence of other systemic metastases,multimodal approaches combining aggressive cytoreductive surgery,intraperitoneal hyperthermic chemotherapy and systemic chemotherapy have been proposed and are actually considered promising methods to improve loco-regional control of the disease,and ultimately to increase survival.The aim of this review article is to present the evidence on treatment of PC in different tumors,in order to provide patients with a proper surgical and multidisciplinary treatment focused on optimal control of their locoregional disease.     

Missing metastases as a model to challenge current therapeutic algorithms in colorectal liver metastases

In oncosurgical approach to colorectal liver metastases, surgery remains considered as the only potentially curative option, while chemotherapy alone represents a strictly palliative treatment. However, missing metastases, defined as metastases disappearing after chemotherapy, represent a unique model to evaluate the curative potential of chemotherapy and to challenge current therapeutic algorithms. We reviewed recent series on missing colorectal liver metastases to evaluate incidence of this phenomenon, predictive factors and rates of cure defined by complete pathologic response in resected missing metastases and sustained clinical response when they were left unresected. According to the progresses in the efficacy of chemotherapeutic regimen, the incidence of missing liver metastases regularly increases these last years. Main predictive factors are small tumor size, low marker level, duration of chemotherapy, and use of intra-arterial chemotherapy. Initial series showed low rates of complete pathologic response in resected missing metastases and high recurrence rates when unresected. However, recent reports describe complete pathologic responses and sustained clinical responses reaching 50%, suggesting that chemotherapy could be curative in some cases. Accordingly, in case of missing colorectal liver metastases, the classical recommendation to resect initial tumor sites might have become partially obsolete. Furthermore, the curative effect of chemotherapy in selected cases could lead to a change of paradigm in patients with unresectable liver-only metastases, using intensive first-line chemotherapy to intentionally induce missing metastases, followed by adjuvant surgery on remnant chemoresistant tumors and close surveillance of initial sites that have been left unresected.     

Improved survival after resection of colorectal liver metastases in patients with unresectable lung metastases

BackgroundModern systemic therapies considerably improve tumour control and thus open the possibility of new surgical approaches in metastatic colorectal cancer. In this retrospective clinical cohort with a comparison group, we investigated whether liver resection in a combined liver–lung-metastasised stage is justified if pulmonary disease is not resected.MethodsFrom 283 patients treated in our institution between 2000 and 2014 for combined colorectal liver- and lung metastases, 35 patients had their pulmonary metastases left in situ while they were eligible for both treatment options: resection versus non-resection of liver metastases. Effectively, 15 of these patients received whereas 20 did not receive a liver resection. In these patients, we compared overall survival and determined risk factors that are associated with poor survival, applying a Cox-Proportional Hazards model.ResultsPatients whose liver metastases were resected showed significantly longer median survival compared to patients who did not undergo hepatic surgery (median 2.6 vs 1.5 years, P = 0.0182). The Cox-Proportional Hazards model revealed hepatic metastasectomy to be the strongest determinant of patient survival (HR 5.27; CI: (1.89, 14.65)).ConclusionOur results suggest that surgical removal of liver metastases may be beneficial in selected patients even if concomitant lung metastases cannot be resected.     

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.     

Treatment strategies for neuroendocrine liver metastases: a systematic review

BackgroundGastroenteropancreatic neuroendocrine tumors are often diagnosed when metastatic. The liver is the main site of metastases. Unfortunately, optimal management of neuroendocrine liver metastases remains a topic of debate. The aim of this study was to make a systematic review of the current literature about the results of the different treatments of neuroendocrine liver metastases.MethodsA systematic review was conducted for English language publications from 1995 to 2021. Outcomes were analyzed according to survival, disease-free survival, and in the case of systemic therapies, progression-free survival.Results5509 patients were analyzed in the review. 67% of patients underwent surgery achieving 5 years overall survival despite only 30% percent without a recurrence. 60% of patients that had received a transplant reached 5 years survival with a low disease-free survival rate (20%). Five-year survival rate was 36.2% for patients undergoing loco-regional therapies.ConclusionSurgical resection is the best treatment when metastases are resectable, with the highest rate of survival, although liver transplantation shows good results for patients not eligible for surgery. Loco-regional therapies may be useful when surgical resection is contraindicated, or selectively used as a bridge to surgery or transplantation. Systemic therapies are indicated in patients for whom curative treatment cannot be obtained.     

Benefit of cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy in patients with isolated peritoneal metastases from colorectal cancer

Background

Ever since Sugarbaker has established the cytoreductive surgery (CRS) in combination with intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC), there is a chance of cure for selected patients with peritoneal metastases from colorectal cancer. Objective of this study was to investigate the benefit of CRS and HIPEC compared to other therapy options in patients with isolated synchronous and metachronous peritoneal metastases of colorectal origin in terms of long-term overall survival.

Methods

A retrospective population-based cohort study, including 370 patients diagnosed with isolated synchronous and metachronous peritoneal metastases of colorectal origin, was carried out. Therefore, data were acquired from the cancer registry at the Regensburg Tumor Center in Bavaria, Germany. Patients’ overall survival (OAS) according to their therapy received was analyzed by means of Kaplan-Meier method and multivariable Cox regression.

Results

Overall median survival was 41.6 months for patients treated with CRS and HIPEC, compared with surgery and chemotherapy (24.0 months, log-rank p?=?0.015), chemotherapy only (14.1 months, p?<?0.001), surgery only (11.4 months, p?<?0.001), and best supportive care (7.9 months, p?<?0.001). This benefit persisted after adjustment for further risk factors in multivariable analysis.

Conclusion

The effect of CRS and HIPEC stands out significantly in comparison to all other therapies. The multimodality approach should be a regular option for patients with isolated peritoneal metastases.

     

Challenges in the multidisciplinary management of stage IV colon and rectal cancer

Colorectal metastases still represent a challenge to all oncologists despite progresses achieved by improved resectability, systemic chemotherapy and targeted therapies. In particular in patients with oligo-metastases, the role of surgical resections has been redefined. Resection is the most effective treatment method for liver metastases performed with curative intent; however, primary rate of resectability is low. Several methods to increase resectability have been developed: conversion chemotherapy, portal vein embolization, two-stage resections, vascular reconstruction of the liver veins, combination of resection and intraoperative ablation. Liver resections can be performed at present with low mortality. Patients with isolated peritoneal metastases, no extra-abdominal disease, low volume tumor and complete surgical cytoreduction do benefit from surgery and hyperthermic intraperitoneal chemotherapy. Several national guidelines recommend multimodality treatment for highly selected patients. The management of stage IV colorectal cancer includes several disciplines with focus on resection. A multidisciplinary evaluation of all patients is of crucial importance to define the treatment sequence and individual strategies for each patient.     

Second-look surgery plus hyperthermic intraperitoneal chemotherapy for patients with colorectal cancer at high risk of peritoneal carcinomatosis: Does it really save lives?

The treatment of peritoneal carcinomatosis (PC) of colorectal origin with cytoreductive surgery(CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) has a 5-year recurrence-free or cure rate of at least 16%, so it is no longer labeled as a fatal disease, and offers prolonged survival for patients with a low peritoneal carcinomatosis index. Metachronous PC of colorectal origin is so predictable that there is a model which has been used to successfully determine the individual risk of each patient. Patients at risk are clearly identified; those with the highest risk have small peritoneal nodules present in the first surgery (70% probability of developing PC), ovarian metastases(60%), perforated tumor onset or intraoperative tumor rupture(50%). Current clinical, biological and imaging techniques still lack sufficient sensitivity to diagnose PC in its initial stages, when CRS plus HIPEC has a greater impact and a higher cure rate. Second-look surgery with HIPEC or prophylactic HIPEC at the time of the first intervention have been proposed as means of preventing and/or anticipating clinical or radiological relapse in at-risk patients. Both techniques have shown a significant decrease in peritoneal relapses and should be considered essential weapons in the management of colorectal cancer.