Impact of the Pringle manoeuvre on the mitochondrial redox state of hepatocytes in colorectal cancer patients with liver metastases.

INTRODUCTION: Novel surgical strategies for metastatic colorectal cancer (CRC) treatment offer survival benefits even in the case of multiple bilobar liver injury. However, an inability to overcome the biological consequences of an ischaemia-reperfusion phenomenon among cancer patients remains an oncological issue throughout the last 3 decades. The aim of this study was to assess the values of molecular markers of the mitochondrial redox state of hepatocytes in CRC patients during liver surgery and Pringle manoeuvre (PM) application. MATERIAL AND METHODS: We conducted a prospective study of 114 CRC patients who underwent liver resection for CRC metastases between March 2017 and December 2020. RESULTS: PM application was associated with higher superoxide radicals (SR) level generation compared to liver surgery without blood inflow control - 0.32 ± 0.12 and 0.42 ± 0.21 nmol/gm raw tissue × min, respectively. Levels of NO-Fe-S cluster protein complexes in liver stump parenchyma in the end of transection with and without PM was 0.35 ± 0.09 RU and 0.16 ± 0.04 RU, respectively. The most significant impact of long-term ischaemia was found to be the rate of SR generation in liver stump: 152.4 ± 24.4 (95% CI: 104.1-200.7), R2 = 0.46, p = 0.001. CONCLUSIONS: PM exacerbates the disruption of the mitochondrial respiratory chain and potentiates SR generation. The redox status molecular markers of the hepatocytes in CRC patients with liver metastases can be used to assess the functional status of organ and tissues and improve the existing surgical strategies.

Comparative study of laparoscopic versus open technique for simultaneous resection of colorectal cancer and liver metastases with propensity score analysis.

BACKGROUND: Laparoscopic liver resection for metastatic colorectal cancer (CRC) remains controversial. The objective of this study was to compare the short-term and mid-term outcomes of patients with CRC undergoing laparoscopic versus open colorectal resection with simultaneous resection for liver metastases. METHODS: A total of 126 patients underwent combined laparoscopic resection of CRC and synchronous colorectal liver metastases between 2008 and 2016. A total of 318 patients were treated by an open approach during the above period. By propensity score matching, 109 patients who underwent laparoscopic resection and 109 patients who had an open approach were compared. Analyzed variables included patient characteristics, tumor features, and short-term and mid-term outcomes. RESULTS: Demographic features and pathologic outcomes were similar in both groups after propensity score matching. Three (2.8%) patients undergoing laparoscopic liver resection experienced conversion to open procedure. There was no difference in hospital stay (p = 0.078), transfusion rate (p = 0.686), or time of bowel function return (p = 0.570) between the two groups. The laparoscopic group and the open approach group also showed similar 3-year overall survival rate (74.4% vs. 79.1%; p = 0.792) and 3-year disease-free survival rate (58.5% vs. 55.2%; p = 0.391). However, postoperative morbidity rate was significantly lower in the laparoscopic group (20.2% vs. 33.0%; p = 0.032). CONCLUSIONS: Laparoscopic colorectal resection with simultaneous resection of liver metastases showed satisfactory oncologic outcomes with some short-term advantages compared to the open approach. Thus, laparoscopic approach could be a good alternative of open approach for simultaneous liver and colon resection in patients with CRC.

Effects of multidisciplinary team on the outcomes of colorectal cancer patients with liver metastases.

BACKGROUND: To evaluate the effect of a multidisciplinary team (MDT) treatment modality on outcomes of patients with colorectal cancer with liver metastases (CRLMs) in China. METHODS: We retrospectively identified 236 (MDT: 46, non-MDT: 190) patients who underwent liver resection or simultaneous resection for primary colorectal cancer and liver metastases with a curative intent for CRLMs at the National Cancer Center between January 2014 and June 2018. A 1:2 propensity score matching (PSM) analysis was used to adjust for differences in baseline characteristics between the MDT group and the non-MDT group. After the 1:2 PSM analysis, 46 patients were assigned to the MDT group, and 83 patients were assigned to the non-MDT group. All statistical analyses were performed using SPSS Statistics, version 22 (Armonk, NY, USA). Statistical significance was set at a 2-sided P<0.05. RESULTS: Before PSM analysis, compared to non-MDT patients, MDT patients had worse biological characteristics and were more likely to have node-positive primary tumors (80.4% vs. 63.2%), multiple liver metastases (73.9% vs. 50.5%), and liver metastases with a bilobar distribution (73.9% vs. 50.5%). However, MDT patients had a tendency towards better overall survival (OS) (P=0.169, median OS: 49.7 months vs. 35.2 months). After PSM analysis, no differences in clinicopathologic parameters were identified between the MDT group and the non-MDT group. Compared to non-MDT patients, MDT patients had a tendency towards better OS (P=0.063, median OS: 49.7 vs. 34.1 months). Multivariate analysis showed that having an MDT (HR, 0.550, 95% CI: 0.309-0.977, P=0.041) was an independent predictor of better OS. CONCLUSIONS: The MDT treatment modality can significantly improve the outcomes of CRLMs patients with poor biological characteristics in China.

Clinical application of stereotactic body radiation therapy for colorectal cancer with liver metastases / 中华放射医学与防护杂志

Objective To evaluate the efficacy of stereotactic body radiation therapy (SBRT) for hepatic metastases from colorectal cancer,and to collect data for the application of this technique.Methods A total of 28 patients from No.306 Hospital of PLA,including 17 male and 11 female with median age of 63.8 (range from 31 to 86),were treated with SBRT for colorectal cancer with liver metastases with 54 lesions in total.The GTV,CTV and PTV were delineated above the enhanced CT scans acquired during normal quiet respiration.CTV was obtained by adding 5 mm isotropic margin from GTV,and PTV was obtained by adding 5 to 10 mm isotropic margin from CTV.Prescription dose line covered 50％-60％ of isodose curve at 3-6 Gy/fraction.The total dose was 39-45 Gy and the biologically equivalent doses(BED)was 50.7-65.3 Gy.The patients were followed-up beginning at 3 months after SBRT.The change in size of the lesion based on enhanced CT or MR scans was evaluated.Toxicity was evaluated and scored according to the RTOG criteria.Local control rate and survival rate were analysed.Results All patients completed the treatment.With median follow-up of 15.1 months (range frome 3 to 30 months),7 patients survived at the end of follow-up.The local control rate (LC) was 79.2％,and 1-and 2-year overall survival rate(OS) were 82.7％ and 48.6％,respectively.There was a close corelation between the size of lesion and the LC.The LC (PR + CR) was much better at the size of lesion less than 14 cm3 than that at the size more than 65 cm3(x2 =4.17,P＜0.05).When the size was more than 180 cm3,the LC was zero.Toxicity included fatigue (60.7％),grade 1 and 2 digestive system toxicity (28.6％),a transient grade 1 and 2 bone marrow suppression (46.4％) and a transient increase in transaminase(17.8％).No grade 3 toxicity and above and late toxicity were observed.Conclusions Stereotactic body radiation therapy could be suggested as the first choice for the selected patients who suffer form colorectal liver metastases,especially for those who cannot undergo surgery.

Minimally invasive surgery for resectable colorectal cancer with liver metastases: a prospective study / 中华肝胆外科杂志

Objective To prospective study the use of minimally invasive surgery (MIS) for colorectal cancer with liver metastases (CRCLM) and to analyze the safety and survival outcomes.Methods 31 patients with resectable CRCLM were enrolled into this study from January 2009 to August 2011.Synchronous or metachronous liver metastases were diagnosed in 26 and 5 patients,respectively.The treatment strategy was discussed and decided by a multi disciplinary team which consisted of experienced colorectal surgeons,hepatic surgeons,medical oncologists,radiologists,and pathologists.Treatment included the use of neoadjuvant chemotherapy,one or two-staged surgery,and suitability to use laparoscopic surg(e)ry.Results Coloproctectomy and partial hepatectomy were carried out in all these patients,and every patient received at least one laparoscopic procedure.The operations in cluded: laparoscopic coloproctectomy plus hepatectomy (n=10),laparoscopic coloproctectomy only (n 18) and laparoscopic partial hepatcctomy only (n=3).One-staged coloproctectomy and hepatectomy were performed in 19 patients who presented with synchronous CRCLM.Colorectal and hepatic specific complications,such as anastomotic leak,liver failure,biliary leak,abdominal infection and abdominal bleeding,were not detected in these pati(e)nts.Neoadjuvant chemotherapy was used in 12 patients.Adjuvant chemotherapy was given to every patient.At a mean follow-up of 23.3 months from the diagnosis of liver metastases,the overall survival and disease-free survival were 87.1％ and 71.0％,respectively.Conclusions MIS for resectable CRCLM in carefully selected patients was safe and feasible.A one staged laparoscopic coloproctectomy and partial hepatectomy was possible.The short-middle oncologic outcomes were acceptable,but the long-term survival was still not clear.