Repeat hepatectomy for colorectal liver metastases: A worthwhile operation?

BACKGROUND AND OBJECTIVES: After curative resection of hepatic colorectal metastases, 10-20% of patients experience a resectable hepatic recurrence. We wanted to assess the expected risk-to-benefit ratio in comparison to first hepatectomy and to determine the prognostic factors associated with survival. METHODS: Twenty-nine patients from a group of 152 patients resected for colorectal liver metastases underwent 32 repeat hepatectomies. RESULTS: In-hospital mortality was 3.5% (1/29 patients); the morbidity after repeat hepatectomy was lower than that after first hepatic resection. Combined extrahepatic surgery was performed on 34.5% of repeat hepatectomies vs. 6.9% of first hepatectomies (P = 0.01). Overall actuarial 3-year survival was 35.1%: four patients have survived more than 3 years and one survived for more than 5 years. The number of hepatic metastases and the carcinoembryonic antigen (CEA) serum levels were significant prognostic factors on univariate analysis. The synchronous resection of hepatic and extrahepatic disease was not associated with a lower survival rate when compared with that of patients without extrahepatic localization: three patients of the former group are alive and disease-free at more than 2 years. CONCLUSIONS: Repeat hepatic resection can provide long-term survival rates similar to those of first liver resection, with comparable mortality and morbidity. The presence of resectable extrahepatic disease must not be an absolute contraindication to synchronous hepatectomy because long-term survival is possible.     

Is resection of colorectal liver metastases after a second‐line chemotherapy regimen justified?

BACKGROUND:

Patient outcomes following resection of colorectal liver metastases (CLM) after second‐line chemotherapy regimen is unknown.

METHODS:

From August 1998 to June 2009, data from 1099 patients with CLM were collected prospectively. We retrospectively analyzed outcomes of patients who underwent resection of CLM after second‐line (2 or more) chemotherapy regimens.

RESULTS:

Sixty patients underwent resection of CLM after 2 or more chemotherapy regimens. Patients had advanced CLM (mean number of CLM ± standard deviation, 4 ± 3.5; mean maximum size of CLM, 5 ± 3.2 cm) and had received 17 ± 8 cycles of preoperative chemotherapy. In 54 (90%) patients, the switch from the first regimen to another regimen was motivated by tumor progression or suboptimal radiographic response. All patients received irinotecan or oxaliplatin, and the majority (42/60 [70%]) received a monoclonal antibody (bevacizumab or cetuximab) as part of the last preoperative regimen. Postoperative morbidity and mortality rates were 33% and 3%, respectively. At a median follow‐up of 32 months, 1‐year, 3‐year, and 5‐year overall survival rates were 83%, 41%, and 22%, respectively. Median chemotherapy‐free survival after resection or completion of additional chemotherapy administered after resection was 9 months (95% confidence interval, 4‐14 months). Synchronous (vs metachronous) CLM and minor (vs major) pathologic response were independently associated with worse survival.

CONCLUSIONS:

Resection of CLM after a second‐line chemotherapy regimen was found to be safe and was associated with a modest hope for definitive cure. This approach represents a viable option in patients with advanced CLM. Cancer 2011;. © 2011 American Cancer Society.     

Survival after cytoreductive surgery for peritoneal metastases in colorectal cancer patients: Does a history of resected liver metastases worsen the prognosis?

BackgroundNowadays, resection of two (liver and peritoneum) concomitant colorectal cancer metastatic sites is no longer contraindicated. However, the oncologic outcomes of resecting peritoneal metastases (PM) occurring more than six months after resection of liver metastases (LM) are unknown.AimThe aim of this study was to compare patients with complete cytoreductive surgery (CRS) with or without a history of previous liver resection (LR).MethodsAnalysis from a prospective database of 74 patients with metachronous PM treated with CRS between 2010 and 2020.ResultsAll patients had PM metachronous to primary, 64 patients underwent CRS alone (CRSa) and 10 CRS more than six months after LR (LR-CRS). There was no statistical difference between the groups for clinical or therapeutic characteristics. There were more signet ring cell/mucinous adenocarcinomas in the CRSa group than in the LR-CRS group (19% vs. 0%, p = 0.049). The median peritoneal cancer index (PCI) was 4 and 6 (p = 0.749) in the LR-CRS and CRSa groups, respectively. Median overall survival (OS) and disease-free survival (DFS) were not statistically different between the two groups with 43.6 and 13 months for the CRSa group and 31.1 months and 9.4 months for LR-CRS. Advanced age was an independent negative prognostic factor for OS and high PCI was limit significant. No prognostic factor for DFS was found.ConclusionsLR before CRS has no major prognostic impact. Resection of iterative liver and peritoneum metastases can achieve long-term survival.     

Management of colorectal cancer patients after resection of liver metastases: can we offer a tailored treatment?

Surgical resection remains the only option of cure for patients with colorectal liver metastases, and no patient should be precluded from surgery. There is much controversy not only regarding the most appropriate therapeutic approach in the neoadjuvant setting but also after surgery is performed. Many patients will experience early relapses but others will be long survivors. We need to establish reliable prognostic and predictive factors to offer a tailored treatment. Several prognostic factors after metastasectomy have been identified: high C-reactive protein levels, a high neutrophil-lymphocyte ratio, elevated neutrophil count and low serum albumin are related to a worst outcome. Elevated CEA and Ki 67 levels, intrahepatic and perihepatic lymph node invasion are also some of the markers related to a worst outcome. In contrast, the administration of preoperative chemotherapy has been associated with a better prognosis after hepatectomy. The administration of adjuvant chemotherapy should be done taking in consideration these factors. Regarding predictive factors, determination of ERCC1, TS, TP and DPD and UGT1 polymorphisms assessment could be considered prior to chemotherapy administration. This would avoid treatment related toxicities and increase this population quality of life.     

Gamma Knife radiosurgery for numerous brain metastases: is this a safe treatment?

Gamma Knife (GK) radiosurgery has recently been employed in patients with numerous brain metastases (METs), even those with 10 or more lesions. However, cumulative irradiation doses to the whole brain (WB), with such treatment, have not been determined.

Since the GammaPlan ver. 5.10 (ver. 5.31 is presently available, Leksell GammaPlan) became available in November 1998, 92 GK procedures have been performed for 80 patients with 10 or more brain METs at our facility. The median lesion number was 17 (range: 10–43) and the median cumulative volume of all tumors was 8.02 cc (range: 0.46–81.41 cc). The median selected dose at the lesion periphery was 20 Gy (range: 12–25 Gy). Based on these treatment protocols, the cumulative irradiation dose was computed.

The median cumulative irradiation dose to the WB was 4.71 (range: 2.16–8.51) Gy. The median brain volumes receiving >2 Gy, >5 Gy, >10 Gy, >15 Gy, and >20 Gy were 1105 (range 410–1501) cc, 309 (46–1247) cc, 64 (13–282) cc, 24 (2–77) cc, and 8 (0–40) cc, respectively.

The cumulative WB irradiation doses for patients with numerous radiosurgical targets were not considered to exceed the threshold level of normal brain necrosis.     

Perioperative chemotherapy for resectable colorectal liver metastases: Where now?

Following the publication of the EORTC trial (40983), perioperative chemotherapy has become the standard of care for all patients with resectable colorectal cancer liver metastases (CRLM). However recently presented data suggest that the earlier advantage seen in progression free survival (PFS) may not translate over into a meaningful overall survival (OS) advantage. At the other end of the spectrum, patients with irresectable but liver limited CRLM continue to be offered treatment based on improving PFS, at the expense of regimens with greater response rates (but maybe poorer PFS rates) that could bring them to potentially curative liver resection. We therefore argue that patients with liver limited CRLM should be managed in three separate groups:

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Group One: those with easily resectable disease who should be offered immediate surgery, followed by adjuvant therapy if considered appropriate.     

Debulking surgery for colorectal liver metastases: Foolish or chance?

Even with the recent advances of surgical techniques and systemic therapies, we are often facing patients with multinodular bilateral disease for whom neither R0 nor R1 resection appears possible to perform. For such extensive cases, the tumor debulking approaches might provide a survival benefit, provided that an objective tumor response is obtained with chemotherapy. Here, we review all the arguments which may defend this strategy and propose some recommendations.     

Is portal infusion chemotherapy uneffective for hepatic recurrence after resection for colorectal cancer?

Sixty-six patients with colorectal cancer were studied regarding effects of prevention of hepatic recurrence in completely performed portal infusion chemotherapy. The regimen was continuous administration of 500-875 mg/body of 5-FU for 7 days and intraportal administration of 10 mg of MMC before and after 5-FU administration. Hepatic recurrence rate was 7.6% and the five year survival rate was 83.3% in portal infusion group, and 16% and 71.3% in the control group; the difference was not significant. However, the hepatic recurrence rate in patients administered more than 4 g of 5-FU was 2.5%; there was a significant difference between the portal group and control group. The five-year survival rate for patients administered more than 4 g of 5-FU was 92.3%, which was significantly higher than at less than 4 g. Excellent effects for prevention of hepatic recurrence and prognosis were obtained in patients administered more than 4 g of 5-FU. Thus, the compliance of 5-FU in portal infusion chemotherapy is important. Also, administration of MMC is suspected to enhance the effect of portal infusion chemotherapy.     

Inoperable colorectal liver metastases: A declining entity?

BackgroundUntreated colorectal liver metastases (CLMs) have a dismal prognosis. Surgery remains the gold standard of treatment, but many patients will have inoperable disease at presentation. Until recently, the outlook for such patients was bleak. The purpose of this review was to report on available options in the treatment CLMs, which would be considered unresectable by conventional evaluation.MethodsInclusion criteria were articles published in English-language journals reporting on either retrospective or prospective cohorts of patients undergoing treatment for conventionally inoperable CLM. Main outcome measures were survival, resectability rates, morbidity and mortality following treatment of the patients’ disease.ResultsImproved chemotherapy regimes and other innovative treatments have opened up new options for such patients and may even render conventionally inoperable disease resectable. The aim of treatment should be down-staging of metastases to achieve resectability, however, other treatments such as ablation may be also be used (either alone or in conjunction with resection).ConclusionA nihilistic attitude to the patient with seemingly inoperable liver metastases should be discouraged. Discussion of such patients at multi-disciplinary meetings is essential in order to plan and monitor treatments.     

Is it necessary to carry out hepatic resection and pulmonary resection to obtain a cure for liver and lung metastases from colorectal cancer ?

If hepatic or pulmonary metastases from colorectal cancer are resectable, we perform the operation, and the 5-year survival rate is 40-50%. Median survival time is over 20 months recently for systemic chemotherapy. However, surgical treatment is the only way to obtain a cure. RFA has the advantage of being minimally invasive. But the local recurrence rate is slightly high. It is important to detect a local recurrence early and perform repeated RFA. Repeated RFA improve the prognosis and get the same overall survival rate of liver resection. If both the hepatic and pulmonary metastases are resectable, we perform both resections, with a good surgical outcome. If we cannot perform a second metastasectomy after first metastasectomy, the prognosis is very poor compared to the prognosis for liver metastasis only or lung metastasis only. It is necessary to add many cases to decide the surgical indication for such cases of both liver and lung metastases.     

Is unexpected peritoneal carcinomatosis still a contraindication for resection of colorectal liver metastases?: Combined resection of colorectal liver metastases with peritoneal deposits discovered intra-operatively

Aims

The discovery of unexpected peritoneal carcinomatosis (PC) at the time of hepatectomy for colorectal liver metastases (CLM) is usually considered a contraindication for continuing resection. The first aim of this study was to assess the long-term outcome of patients operated for CLM, and who presented unexpected PC during laparotomy. The second aim was to identify preoperative predictors of PC.

Methods

All patients at a single center between 1985 and 2010 who had unexpected PC, discovered during planed resection of CLM, and negative preoperative imaging for PC were selected. Clinicopathological data were retrospectively analyzed to assess survival outcomes and to identify predictors of unexpected PC.

Results

Out of the 1340 operated patients for CLM, 42 (3%) had unexpected PC. Only patients (n = 30; 71%) who had PC limited to two abdominal regions (Median peritoneal cancer index (PCI): 2 (1–6)) were resected. Twelve patients were not resected due to the extent of peritoneal disease. The overall survival of the 30 patients resected for CLM who had limited PC was 18% at 5 years (median: 42 months). On multivariate analysis, a previous history of PC, a pT4 stage and bilobar CLM were independent predictors of unexpected PC.

Conclusion

Unexpected PC should not be a contraindication for resection provided that the PCI is low and complete resection of all peritoneal and hepatic lesions can be achieved. Previous history of PC, a pT4 primary tumor and bilobar CLM are associated with increased risk of unexpected PC.     

Major hepatectomy for intrahepatic cholangiocarcinoma or colorectal liver metastases. Are we talking about the same story?

IntroductionMajor hepatectomy (MH) is often needed in the curative management of intrahepatic cholangiocarcinoma (IHCC) and colorectal liver metastases (CRLM). While similar outcomes could be expected after MH for IHCC and CRLM, outcomes seem worse after MH for IHCC. A better understanding of such differences might help improving perioperative outcomes but comprehensive analysis are lacking.MethodsAll patients undergoing curative intent MH for IHCC or CRLM from 2003 to 2009 were included from two dedicated multi-institutional datasets. Preoperative management and short-term outcomes after MH were first compared. Independent predictors of postoperative mortality and morbidity were identified.ResultsAmong 827 patients, 333 and 494 patients underwent MH for IHCC and CRLM, respectively. Preoperative portal vein embolization was more frequently performed in the CRLM group (p < 0.001). MH in the IHCC group required more extended resection (p < 0.001). Postoperative mortality and severe morbidity rates were significantly higher in the IHCC group (7.2% vs. 1.2% and 29.7% vs. 11.1%, p < 0.001, respectively). Main causes for mortality were postoperative liver failure and deep surgical site infection. MH for IHCC was an independent risk factor for mortality (p < 0.001) and severe morbidity (p < 0.001). After propensity score matching (212 patients in each group), the aforementioned differences regarding outcomes remained statistically significant.ConclusionThis study suggests that IHCC patients are inherently more at risk after MH as compared to CRLM patients. Considering that postoperative liver failure was the most frequent cause of death, preoperative planning might have been inadequate in the setting of IHCC while more complex/extended resections should be expected.     

Hepatic arterial 5-fluorouracil in patients with liver metastases of colorectal?cancer: Single-centre experience in 145 patients

Background:Hepatic arterial chemotherapy for liver metastases ofcolorectal cancer is still under discussion. Mainly because of the technicalcomplications of this mode of treatment and the lack of a survival benefit inrandomized studies. We performed an analysis of hepatic arterial5-fluorouracil (5-FU) chemotherapy in 145 consecutive patients treated at asingle institution. Patients and methods:One hundred forty-five patients withinoperable liver metastases from colorectal cancer were included. 5-FU, 1000mg/m²/day continuous infusion for five days every three weeks, wasdelivered in the hepatic artery by percutaneous catheter or arterial accessdevice. Results:The response rate was 34% for all patients,40% in patients with extrahepatic disease, and 15% in patientswith i.v. 5-FU-based pretreatment. TTP and OS for all patients were 7.5 and14.3 months, respectively. In patients with extrahepatic disease or i.v.5-FU-based pretreatment, OS was significantly shorter compared to patientswithout extrahepatic disease or 5-FU-based pretreatment (9.7 vs. 19.3 monthsand 10.1 vs. 17.4 months, respectively). forty-seven percent of patientsstopped treatment because of a complication. Complications most often seen inpatients with arterial ports were hepatic artery thrombosis (48%) anddislocation of the catheter (22%). Conclusions:The results of our analysis are in line with previousphase III studies. Extrahepatic disease and i.v. 5-FU-based pretreatment wereprognostic for reduced OS. The complication rate of hepatic arterial deliverywas worrisome, although, no negative impact on survival could be established.There is a strong need for improvement of hepatic arterial delivery methodsbefore further evaluation of hepatic arterial 5-FU will be worthwhile.     

Is hepatic transplantation justified for primary liver cancer?

A concise, yet objective overview of Hepatocellular Carcinoma (HCC) treatment in 2006 with an intent to transplant is presented. The most significant variables impacting on the use of hepatic transplantation as therapy for primary liver cancer are developed under the headings of: Staging Criteria; Organ allocation; Transplant dropout minimization therapies; and Effects on the HCC general population. The pertinent medical literature and update of an ongoing intent-to-treat HCC with transplant single center randomized control trial are reviewed.