Perioperative chemotherapy and liver resection for hepatic metastases of colorectal cancer

Surgical resection has played a major role in the treatment for colorectal liver metastases. The safety and efficacy of surgery for liver metastasis are obvious, although there are some differences between the western countries and Japan concerning the surgical indication, procedures, timing of chemotherapies in a perioperative period, and treatment of a primary disease. In future, long-term outcomes after surgical resection for colorectal liver metastases would be expected to be prolonged by combination of surgery and chemotherapies.     

Synchronous resection of colorectal cancer primary and liver metastases: an outcomes analysis

BackgroundConcurrent resection of the primary cancer and synchronous colorectal cancer liver metastases (CRCLM) was evaluated for differences in outcomes following stratification of both the liver and colorectal resection.MethodsConsecutive cases of synchronous resection of both the CRC primary and CRCLM were reviewed retrospectively at a single, high-volume institution over a 17-year period (2000–2017).Results273 patients underwent simultaneous resection of CRCLM. The distribution of the primary lesion was similar between the colon (52.4%) and rectum (47.6%), while 46.9% of patients had bilobar liver disease. Major liver/major colorectal resection (n = 24) were significantly more likely to experience colorectal specific morbidity (OR 3.98, 95% CI 1.56–10.15, p = 0.004), liver specific morbidity (OR 7.4, 95% CI 2.22–24.71, p = 0.001), total morbidity (OR 2.91, 95% CI 1.18–7.18, p = 0.020) and 90-day mortality (OR 5.50, 95% CI 1.27–23.81, p = 0.023). Failure to receive adjuvant chemotherapy secondary to postoperative morbidity was associated with significantly worsened survival (HR for death 5.91, 95% CI 1.59–22.01, p = 0.008).ConclusionsPostoperative morbidity precluding the administration of adjuvant chemotherapy is associated with an increase in mortality. Combining a major liver with major colorectal resection is associated with a significant increase in major morbidity and 90-day mortality, and should be avoided.     

Perioperative blood transfusion in cancer patients undergoing laparoscopic colorectal resection: risk factors and impact on survival

Background

Perioperative blood transfusion has been associated with a poor prognosis in patients undergoing surgery for colorectal cancer. The aim of this study was to evaluate risk factors for blood transfusion and its impact on long-term outcome exclusively in patients undergoing laparoscopic surgery for curable colorectal cancer.

Methods

Data were retrieved from a prospectively collected database of patients who underwent laparoscopic surgery for curable colorectal cancer over a 6-year period. Long-term data were collected from our outpatient clinic and personal contact when necessary.

Results

Two hundred and one patients underwent laparoscopic surgery for curable colorectal cancer (stage I–III). Sixty-eight (33.8 %) received blood transfusions during or after surgery. These patients were typically older, had lower preoperative hemoglobin levels, had a more advanced cancer, had a higher Charlson score, had a higher rate of complications and had a higher conversion rate. Kaplan–Meier overall survival analysis was significantly worse in patients who received blood transfusions (P = 0.004). Decreased disease-free survival was also observed in transfused patients; however, this did not reach statistical significance (P = 0.21). A multivariate analysis revealed that transfusion was not an independent risk factor for decreased overall and disease-free survival. The Charlson score was the only independent risk factor for overall survival (OR = 2.1, P = 0.002). Independent factors affecting disease-free survival were stage of disease, Charlson score and, to a lesser degree, age and body mass index.

Conclusions

Perioperative blood transfusion is associated with decreased long-term survival in patients undergoing laparoscopic resection for colorectal cancer. However, this association apparently reflects the poorer medical condition of patients requiring surgery and not a causative relationship.     

Simultaneous resection of colorectal cancer with synchronous liver metastases; a practice survey

BackgroundWe examined surgeon practice intentions and barriers to performing simultaneous resections for colorectal cancer with synchronous liver metastases.MethodsWe electronically surveyed North American surgeons who provide colorectal cancer care with a pilot-tested questionnaire. Four clinical scenarios of increasing complexity were presented. Perceived outcomes of and barriers to simultaneous resection were assessed on a 7-point Likert scale. We compared results between general and hepatobiliary surgeons.ResultsResponses (rate 20%, 234/1166) included 50 general and 134 hepatobiliary surgeons. High likelihood scores for support of simultaneous resection among general and hepatobiliary surgeons, respectively, included the following for: minor liver and low complexity colon, 83% and 98% (p < 0.001); minor liver and rectal resection, 57% and 73% (p = 0.042); complex liver and low complexity colon resection, 26% and 24% (p = 0.858); and, complex liver and rectal resection, 11% and 7.0% (p = 0.436). Among hepatobiliary surgeons, the most common barriers to simultaneous resections were patient comorbidities and lung metastases, whereas certain general surgeons additionally identified transfer of care.ConclusionsSurgeon support for simultaneous resection was high for cases with minor hepatectomy, and low for cases involving major hepatectomy. These results suggest that clinical trials should involve patients with limited disease to evaluate post-operative complications and cost.     

Perioperative blood transfusion increases the risk of recurrence in colorectal cancer

A retrospective study was conducted on 519 patients undergoing curative resection for colorectal carcinoma between 1969 and 1980. Recurrence was diagnosed in 214 patients (41.2 percent), 179 of whom (34.5 percent) had received blood transfusions and 35 of whom (6.7 percent) had not (P<.001). Exclusion of the right-sided colonic tumors still showed that recurrence was more common in transfused than nontransfused patients (135 [47.2 percent] vs. 25 [22.5 percent];P<.001). Recurrence in patients transfused only during surgery (N=201) was higher than in nontransfused patients (P<.001) and, similarly, all patients transfused during surgery (N=297) had an increased risk (P<.001). Among patients with rectal cancer, transfusion increased the risk of recurrence in those treated by abdominoperineal resection (P<.02), but this was not the case in those treated by sphincter-saving resection (P=.2). Hierarchical log linear analysis of all dependent factors (Dukes' stage, histologic grade, age, sex, site, elective, or emergency procedure) showed that Dukes' stage and blood transfusion had the most significant effects on the development of recurrence (χ²=54.04, df=6,P<.0001 and χ²=13.93, df=3,P<.003). The risk of recurrence following curative surgery for colorectal cancer is markedly increased by blood transfusion on the day of operation. Poster presentation at the meeting of the American Society of Colon and Rectal Surgeons, Anaheim, California, June 12 to 17, 1988.     

Perioperative chemotherapy with bevacizumab and liver resection for colorectal cancer liver metastasis

Background:

Surgery remains the only curative option for patients with colorectal cancer liver metastases (CRLM). Perioperative chemotherapeutic strategies have become increasingly popular in the treatment of CRLM. Although the role of bevacizumab (Bev) in this setting remains unclear, its widespread use has raised concerns about the use of Bev as part of perioperative chemotherapy.

Methods:

We retrospectively reviewed all patients who received Bev and underwent liver resection between July 2004 and July 2008 at the McGill University Health Center. Chemotherapy-related toxicity, response to chemotherapy, surgical morbidity and mortality, liver function and survival data were assessed.

Results:

A total of 35 patients were identified. Of these, 26 (74.3%) patients received oxaliplatin-based cytotoxic chemotherapy, six (17.1%) received irinotecan-based therapy and the remainder received both agents. A total of 17 patients (48.6%) underwent portal vein embolization prior to resection and 12 (34.3%) underwent staged resection for extensive bilobar disease. A median of six cycles of preoperative Bev were administered. Nine patients (25.7%) experienced grade 3 or higher chemotherapy-related toxicities. Four events were deemed to be related to Bev. The overall response rate was 65.7% (complete and partial response). One patient progressed on therapy, but this did not prevent R0 resection. The incidence of postoperative morbidity was 42.3%. A total of 21.7% of complications were Clavien grade 3 or higher. There were no perioperative mortalities. There were no cases of severe sinusoidal injury or steatohepatitis. The Kaplan–Meier estimate of 4-year survival was 52.5%.

Conclusions:

These data confirm the safety of chemotherapy regimens which include Bev in the perioperative setting and demonstrate that such perioperative chemotherapy in patients with CRLM does not adversely affect patient outcome. There was no increase in perioperative morbidity compared with published rates. The addition of Bev to standard chemotherapy may improve response rates, which may, in turn, impact favourably on patient survival.     

Repeated liver resection for recurrent metastases from colorectal cancer

BACKGROUND/AIMS: Repeat hepatectomy is the most effective treatment for recurrent colorectal liver metastases. We aim to assess how repeated liver resections increase survival, without unacceptable surgical risk. METHODOLOGY: Between December 1992 and December 1998, among 19 patients, 5 underwent secondary resection of recurrent metastatic disease. Following the primary liver surgery, three patients had systemic chemotherapy with 5-fluorouracil and two locoregional chemotherapy via Port-a-cath in the gastroduodenal artery. We evaluated survival and we compared time of surgery, duration of Pringle maneuver, blood losses and postoperative stay in the hospital between first and second liver surgery. RESULTS: Perioperative mortality at second liver resection was nil; morbidity minor; mean duration of surgery 320 vs. 260 min; Pringle maneuver 35 vs. 25 min; blood losses 1300 vs. 650 mL; postoperative stay 12.6 vs. 11.5 days. Mean total survival from time of colon resection was 50 months. As an interesting secondary finding, we observed prolonged inhibition of liver regeneration following treatment with Methotrexate. CONCLUSIONS: Repeated hepatic resection is a safe procedure for selected patients. Surgical risk is slightly increased, but the risk/benefit ratio is definitely in favor of as many repeated resections as needed, whenever there is a chance of curative surgery.     

Open liver resection for colorectal metastases: better short- and long-term outcomes in patients potentially suitable for laparoscopic liver resection

Background:

There is no prospective randomized data comparing laparoscopic to open hepatectomy. This study compared short- and long-term outcomes in patients undergoing hepatectomy for colorectal metastases (CRM), who were suitable for either laparoscopic or open surgery.

Methods:

Data were prospectively collected from consecutive patients undergoing hepatic resection of CRM at a single centre (1987–2007). Patients who were suitable for laparoscopic resection (Group 1) were compared with patients whose tumour characteristics would best be considered for open resection (Group 2).

Results:

Out of 1152 hepatectomies, 266 (23.1%) were deemed suitable for a laparoscopic approach. The median (IQR) number of metastases was greater in Group 2 [2(1–20) vs. 1(1–10), P < 0.001], as was the mean (SD) tumour size [5.3(3.6) cm vs. 3.3(1.2) cm, P < 0.001]. The median (IQR) operation time [210 (70) min vs. 240 (90) min, P < 0.001] and blood loss [270 (265) ml vs. 355 (320) ml, P < 0.001] were less in Group 1. There was no difference in length of stay, morbidity or mortality. Patients in Group 2 had a higher R1 resection rate (14.9%) compared with Group 1 (4.5%, P < 0.001) and lower 5-year survival (37.8% vs. 44.2%, P= 0.005).

Discussion:

Current criteria for laparoscopic hepatectomy selects patients who have more straight-forward surgery, with less risk of an involved resection margin and better long-term survival, compared with patients unsuited to a laparoscopic approach. Clearly defined criteria for laparoscopic hepatectomy are essential to allow meaningful analysis of outcomes and the results of unrandomized series of laparoscopic hepatectomies must be interpreted with caution.     

Outcome after repeat resection of liver metastases from colorectal cancer

Introduction

Although advances in multimodal treatment have led to prolongation of survival in patients after resection of colorectal liver metastasis (CRC-LM), most patients develop recurrence, which is often confined to the liver. Repeat hepatic resection (RHR) may prolong survival or even provide cure in selected patients. We evaluated the perioperative and long-term outcomes after RHR for CRC-LM in a single institution series.

Patients and methods

Since 1999, 92 repeat hepatic resections (63 % wedge/segmental, 37 % hemihepatectomy or greater) for recurrent CRC-LM were performed in 80 patients. Median interval from initial liver resection to first RHR was 1.25 years. Any kind of chemotherapy (CTx) had been given in 88 % before RHR. Neoadjuvant CTx was given in 38 %.

Results

Hepatic margin-negative resection was achieved in 79 %. Mortality was 3.8 %. Overall complication rates were 53 %, including infection (17 %), operative re-intervention (12 %), and hepatic failure (5.4 %). Overall 5-year survival after first RHR was 50.3 %. Univariately, primary tumor stage, the extent of liver resection, postoperative complications, and the overall resection margin correlated with survival. By multivariate analysis, primary T stage, size of metastasis, and overall R0 resection influenced survival. Survival was not independently influenced by hepatic resection margins or (neoadjuvant) CTx.

Conclusions

Repeat hepatic resection for recurrent CRC-LM can be performed with low mortality and acceptable morbidity. Survival after repeat hepatic resection in this selected group of patients is encouraging and comparable to results after first liver resections.     

Mini-invasive vs open resection of colorectal cancer and liver metastases: A meta-analysis

BACKGROUND The safety and feasibility of the simultaneous resection of primary colorectal cancer (CRC) and synchronous colorectal liver metastases (SCRLM) have been demonstrated in some studies. Combined resection is expected to be the optimal strategy for patients with CRC and SCRLM. However, traditional laparotomy is traumatic, and the treatment outcome of minimally invasive surgery (MIS) is still obscure. AIM To compare the treatment outcomes of MIS and open surgery (OS) for the simultaneous resection of CRC and SCRLM. METHODS A systematic search through December 22, 2018 was conducted in electronic databases (PubMed, EMBASE, Web of Science, and Cochrane Library). All studies comparing the clinical outcomes of MIS and OS for patients with CRC and SCRLM were included by eligibility criteria. The meta-analysis was performed using Review Manager Software. The quality of the pooled study was assessed using the Newcastle-Ottawa scale. The publication bias was evaluated by a funnel plot and the Begg’s and Egger’s tests. Fixed- and random-effects models were applied according to heterogeneity. RESULTS Ten retrospective cohort studies involving 502 patients (216 patients in the MIS group and 286 patients in the OS group) were included in this study. MIS was associated with less intraoperative blood loss [weighted mean difference (WMD)=-130.09, 95% confidence interval (CI):-210.95 to -49.23, P = 0.002] and blood transfusion [odds ratio (OR)= 0.53, 95%CI: 0.29 to 0.95, P = 0.03], faster recovery of intestinal function (WMD =-0.88 d, 95%CI:-1.58 to -0.19, P = 0.01) and diet (WMD =-1.54 d, 95%CI:-2.30 to -0.78, P < 0.0001), shorter length of postoperative hospital stay (WMD =-4.06 d, 95%CI:-5.95 to -2.18, P < 0.0001), and lower rates of surgical complications (OR = 0.60, 95%CI: 0.37 to 0.99, P = 0.04). However, the operation time, rates and severity of overall complications, and rates of general complications showed no significant differences between the MIS and OS groups. Moreover, the overall survival and disease-free survival after MIS were equivalent to those after OS. CONCLUSION Considering the studies included in this meta-analysis, MIS is a safe and effective alternative technique for the simultaneous resection of CRC and SCRLM. Compared with OS, MIS has less intraoperative blood loss and blood transfusion and quicker postoperative recovery. Furthermore, the two groups show equivalent long-term outcomes.     

Simultaneous versus staged liver resection of synchronous liver metastases from colorectal cancer

Background and aims The surgical strategy for treatment of synchronous liver metastases from colorectal cancer remains controversial. This retrospective analysis was conducted to compare the postoperative outcome and survival of patients receiving simultaneous resection of liver metastases and primary colorectal cancer to those receiving staged resection. Materials and methods Between January 1988 and September 2005, 219 patients underwent liver resection for synchronous colorectal liver metastases, of whom, 40 patients received simultaneous resection of liver metastases and primary colorectal cancer, and 179 patients staged resections. Patients were identified from a prospective database, and records were retrospectively reviewed. Patient, tumor, and operative parameters were analyzed for their influence on postoperative morbidity and mortality as well as on long-term survival. Results Simultaneous liver resections tend to be performed for colon primaries rather than for rectal cancer (p = 0.004) and used less extensive liver resections (p < 0.001). The postoperative morbidity was comparable between both groups, whereas the mortality was significantly higher in patients with simultaneous liver resection (p = 0.012). The mortality after simultaneous liver resection (n = 4) occurred after major hepatectomies, and three of these four patients were 70 years of age or older. There was no significant difference in long-term survival after formally curative simultaneous and staged liver resection. Conclusion Simultaneous liver and colorectal resection is as efficient as staged resections in the treatment of patients with colorectal cancer and synchronous liver metastases. To perform simultaneous resections safely a careful patient selection is necessary. The most important criteria to select patients for simultaneous liver resection are age of the patient and extent of liver resection.     

The effects of resection margin and KRAS status on outcomes after resection of colorectal liver metastases

BackgroundThe aim of this study was to investigate the influence of resection margin status in patients with KRAS mutations (mt-KRAS) when compared to those with wild-type KRAS (wt-KRAS) on long-term outcomes in patients with resected CRLM.MethodsAll patients who underwent resection of CRLM with curative intent between January 2011 and December 2016 and had a KRAS type recorded were included in the study. Overall survival (OS), as well as death-censored overall (RFS) and liver-specific (LS-RFS) recurrence-free survival between KRAS types and the margin status within KRAS subgroups were compared using Cox regression models.ResultsData were available for N = 500 patients (30.4% mt-KRAS). mt-KRAS status was independently associated with significantly shorter OS. Within the wt-KRAS subgroup, smaller margins were found to be associated with significantly shorter death-censored LS-RFS (p < 0.001), with HRs of 1.93 (p = 0.005) for 1–4 mm margins and 2.83 (p < 0.001) for <1 mm margins, relative to those with clear margins. No such association was observed in the mt-KRAS subgroup (p = 0.721).ConclusionThe resection margin status is of greater importance in patients with wt-KRAS. Such information could be useful in the operative planning, especially for those with multiple metastatic deposits, and also in the post-operative counselling and surveillance based on the margin and KRAS status.     

Aggressive liver resection including major-vessel resection for colorectal liver metastases

AIM: To clarify short- and long-term outcomes of combined resection of liver with major vessels in treating colorectal liver metastases.METHODS: Clinicopathologic data were evaluated for 312 patients who underwent 371 liver resections for metastases from colorectal cancer. Twenty-five patients who underwent resection and reconstruction of retrohepatic vena cava, major hepatic veins, or hepatic venous confluence during hepatectomies were compared with other patients, who underwent conventional liver resections.RESULTS: Morbidity was 20% (75/371) and mortality was 0.3% (1/312) in all patients after hepatectomy. Hepatic resection combined with major-vessel resection/reconstruction could be performed with acceptable morbidity (16%) and no mortality. By multivariate analysis, repeat liver resection (relative risk or RR, 5.690; P = 0.0008) was independently associated with resection/reconstruction of major vessels during hepatectomy, as were tumor size exceeding 30 mm (RR, 3.338; P = 0.0292) and prehepatectomy chemotherapy (RR, 3.485; P = 0.0083). When 312 patients who underwent a first liver resection for initial liver metastases were divided into those with conventional resection (n = 296) and those with combined resection of liver and major vessels (n = 16), overall survival and disease-free rates were significantly poorer in the combined resection group than in the conventional resection group (P = 0.02 and P < 0.01, respectively). A similar tendency concerning overall survival was observed for conventional resection (n = 37) vs major-vessel resection combined with liver resection (n = 7) performed as a second resection following liver recurrences (P = 0.09). Combined major-vessel resection at first hepatectomy (not performed; 0.512; P = 0.0394) and histologic major-vessel invasion at a second hepatectomy (negative; 0.057; P = 0.0005) were identified as independent factors affecting survival by multivariate analysis.CONCLUSION: Hepatic resection including major-vessel resection/reconstruction for colorectal liver metastases can be performed with acceptable operative risk. However, such aggressive approaches are beneficial mainly in patients responding to effective prehepatectomy chemotherapy.     

Perioperative blood transfusion and prognosis in colorectal cancer. Analysis of a series]

The relationship between survival after surgical resection of colorectal carcinoma, and perioperative blood transfusion was studied retrospectively. "Curative" surgery was performed in 164 cases of colorectal cancer--stages B and C--, 72 of them received red-cell concentrates perioperatively. Multiple regression analysis did not show any deleterious effect of blood transfusion on the survival of the surgically treated patients (P = 0.941). The volume of the blood derivative received neither seems to influence their outlook. As it was expected a higher rate of transfusion occurred among rectal cancer patients. Mechanisms and factors involved in this controverted issue are discussed and literature is widely reviewed.     

The argument for liver resection in colorectal liver metastases

The first liver resection for colorectal metastasis was performed by Cattell in 1940. Unfortunately, there has never been a randomized control trial for liver resection against other treatment modalities (best supportive care, palliative chemotherapy, etc). Since this operation is now well established in the surgical repertoire, it would now be ethically difficult to undertake such a trial.     

Prognostic factors following liver resection for hepatic metastases from colorectal cancer

BACKGROUND/AIMS: We aimed to identify prognostic factors that may allow better patient selection for liver resection for colorectal liver metastases. METHODOLOGY: A retrospective analysis of the files of 120 patients undergoing liver resection for colorectal metastases between 9/85 and 12/96 was performed. Survival and disease-free survival were calculated, and a uni- and multivariate analysis for the prognostic impact of various perioperative factors on survival was performed. RESULTS: Perioperative morbidity and mortality were 28.3% and 5.8% respectively. Median overall survival was 30 months with a 5-year survival rate of 31%. Radicality was the prime prognostic determinant. In patients with R0-resection, a liver metastasis of > 3.5 cm in diameter was the only independent factor associated with an adverse prognosis. CONCLUSIONS: Liver resection for colorectal liver metastases should be attempted if complete resection with clear margins is feasible and may be especially beneficial in patients with small (< or = 3.5 cm) lesions.     

Prognostic factors following liver resection for hepatic metastases from colorectal cancer

AIM: To determine the impact of prognostic factors on survival of patients with metastases from colorectal cancer that underwent liver resection. METHODS: The records of 28 patients that underwent liver resection for metastases from colorectal cancer between April 1992 and September 2001 were retrospectively analyzed. Thirty-eight resections were performed (more than one resection in eight patients and two patients underwent re-resections). The primary tumor was resected in all the patients. A screening protocol for liver metastases including clinical examinations every three months, ultrassonography and CEA level until 5 years of follow-up and after every 6 months, was applied. The prognostic factors analyzed regarding the impact on survival were: Dukes C stage of primary tumor, size of metastasis >5 cm, a disease-free interval from primary tumor to metastasis < 1 year, CEA level > 100 ng/mL, resection margins < 1 cm and extrahepatic disease. The Kaplan-Meier curves, log rank and Cox regression were used for the statistical analysis. RESULTS: Perioperative morbidity and mortality were 39.3% and 3.6%, respectively. The 5-year survival rate was 35%. The independent prognostic factors were: disease-free interval from primary tumor to metastasis < 1 year and extrahepatic disease. CONCLUSIONS: The liver resection for metastases from colorectal cancer is a safe procedure with more than 30% 5-year survival. Disease-free interval from primary tumor to metastasis < 1 year and extrahepatic disease were independent prognostic factors.