KRAS Gene Mutation in Patients Undergoing Liver Resections for Colorectal Cancer. Is There an Advantage to Anatomical Resections?

Introduction: Several factors have been described to make a prognostic assessment of patients with liver metastases due to colorectal cancer and to define the benefit of the surgical management of metastatic involvement; one of these factors is the status of the KRAS gene since its mutation is associated with worse outcomes. This study aims to describe the outcomes for a retrospective series of patients after liver resections for metastatic colorectal cancer concerning KRAS gene status. Materials and methods: The study involves a retrospective cohort of patients undergoing liver metastasectomy for colorectal cancer with KRAS mutation study from 2009-2013 at the National Institute of Cancerology in Colombia. Five-year survival analyses (overall and disease-free) were performed according to KRAS mutation status and the type of liver resection performed using the Kaplan-Meier estimate. Results: 35 patients undergoing liver metastasectomy were analyzed, of which 42.8% had KRAS gene mutation. Median overall survival was 34.2 months for patients with KRAS- mutant and 46.5 for non-mutant. The median survival for KRAS-mutant patients with anatomic resections was 43.5 months versus 23.5 months for nonanatomic resections. Conclusions: Performing anatomic resections during liver metastasectomy in patients with KRAS mutants could be associated with an improvement in overall survival. It is necessary to continue building the evidence for adequate decision-making in patients with KRAS mutants who will undergo liver resections.

Introducción: se han descrito varios factores para realizar una evaluación pronóstica de los pacientes con metástasis hepáticas por cáncer colorrectal y definir el beneficio en el manejo quirúrgico del compromiso metastásico; uno de estos factores es el estado del gen KRAS, debido a que su mutación está relacionada con peores desenlaces. El objetivo de este estudio es describir los desenlaces para una serie retrospectiva de pacientes después de resecciones hepáticas por metástasis de cáncer colorrectal en relación con el estado del gen KRAS. Metodología: cohorte retrospectiva de pacientes llevados a metastasectomía hepática por cáncer colorrectal con estudio de mutación KRAS durante el período 2009-2013, en el Instituto Nacional de Cancerología en Colombia. Se realizaron análisis de supervivencia a 5 años (global y libre de enfermedad) según el estado de mutación KRAS y según el tipo de resección hepática realizada mediante el método de Kaplan-Meier. Resultados: se analizaron a 35 pacientes llevados a metastasectomía hepática, de los cuales el 42,8% presentaba mutación del gen KRAS. La supervivencia global media fue de 34,2 meses para los pacientes con KRAS mutado y de 46,5 para los no mutados. La supervivencia media para los pacientes con KRAS mutado con resecciones anatómicas fue de 43,5 meses frente a 23,5 meses en los que se realizaron resecciones no anatómicas. Conclusiones: realizar resecciones anatómicas durante la metastasectomía hepática en los pacientes con KRAS mutado podría estar asociado con una mejoría en la supervivencia global. Se requiere continuar en la construcción de la evidencia que permita una adecuada toma de decisiones de los pacientes con KRAS mutado que serán llevados a resecciones hepáticas.

Comparison of the effects of laparoscopic versus open liver resection for colorectal cancer liver metastasis on the surgery-chemotherapy interval: a propensity score matching analysis / 中华肝胆外科杂志

Objective:To compare the effects of laparoscopic versus open liver resection for colorectal cancer liver metastasis on the interval between surgery and chemotherapy, the perioperative outcomes and the prognosis of patients.Methods:A total of 127 patients undergoing colorectal cancer liver metastasis resection in the Department of General Surgery, Huashan Hospital, Fudan University, from January 2014 to February 2023 were retrospectively analyzed, including 81 males and 46 females, aged (60.0±8.9) years. Based on surgical approaches, the patients were divided into the laparoscopic group ( n=33) and the open group ( n=94). After propensity score matching (PSM), 26 cases in the laparoscopic group were matched with 45 cases in the open group. The maximum tumor diameter, proportion of tumors involving both lobes, and proportion of solitary tumors, interval between surgery and first cycle of chemotherapy, postoperative complications, postoperative hospital stay and the prognosis of patients were compared between the two groups after matching. Survival curves and rates were analyzed by Kaplan-Meier and log-rank test. Results:After PSM, there were no significant differences in the baseline data of patients, including tumor maximum diameter, proportion of tumors involving both lobes, and proportion of solitary tumors between the two groups (all P>0.05), indicating comparability. After matching, the interval between surgery and first cycle of chemotherapy in the laparoscopic group (34.4±11.2) d was shorter than that in the open group (46.7±28.0) d, the laparoscopic group had a lower incidence of postoperative complications[0 vs 20.0%(9/45)] and a shorter postoperative hospital stay[6.0 (5.0, 6.2) d vs 8.0 (7.0, 11.5) d] compared to the open group (all P<0.05). There was no significant difference in the recurrence-free survival rate (χ 2=3.27, P=0.070) and the cumulative survival rate (χ 2=0.001, P=0.974) between the two groups. Conclusion:In patients with colorectal cancer liver metastasis, laparoscopic liver surgery showed a lower incidence of postoperative complications and a shorter postoperative hospital stay compared to open surgery. The interval between surgery and first cycle of chemotherapy is shorter after laparoscopic surgery. The long-term prognosis is comparable in the laparoscopic and open surgery.

Efficacy of microwave ablation versus radiofrequency ablation in the treatment of colon cancer liver metastases: a meta-analysis / 中华肝胆外科杂志

Objective:To explore the best treatment for local ablation of colon cancer liver metastases (CRLM) by meta-analysis.Methods:The electronic databases of PubMed, Web of Science, Embase, CNKI and the Cochrane Library were searched from the establishment to August 22, 2022, and studies that report outcomes with comparison between microwave ablation (WMA) and radiofrequency ablation (RFA) in CRLM treatment were selected by inclusion and exclusion criteria. Furthermore, the perioperative and survival data were statistically summarized and analyzed by Review Manager 5.3 software.Results:A total of 5 retrospective studies were included with a total sample size of 648 cases, including 316 cases (48.8%) in the WMA group and 332 cases (51.2%) in the RFA group. The results of meta-analysis showed that locoregional recurrence rate in WMA group was significantly lower than that in RFA group. The 1-year and 2-year disease-free survival (DFS) of the WMA group was significantly better than that of the RFA group with HR of 1.77 ( P=0.04, 95% CI: 1.04-3.02) and 1.60 ( P=0.02, 95% CI: 1.09-2.35), respectively. Conclusion:The local control rate and 1-year and 2-year DFS of WMA were superior to RFA.

Minutes of seminar on 2023 multi-center cooperation project of liver transplantation for metastatic liver cancer in China / 器官移植

Led by Zheng Shusen, Academician of Chinese Academy of Engineering (CAE) from Zhejiang University, the first multi-center cooperation project of liver transplantation for metastatic liver cancer in China, gathering 28 liver transplantation centers nationwide, was launched in Shanghai. All participating experts conducted in-depth exchanges and discussions regarding four topics including inclusion criteria of liver transplantation for metastatic liver cancer, the risk assessment and prognostic evaluation of liver transplantation for metastatic liver cancer, perioperative medication of liver transplantation for metastatic liver cancer, and the implementation details of multi-center cooperation project. Questionnaires were distributed to reach consensus and pinpoint the directions, aiming to carry out high-quality and standardized clinical researches on liver transplantation for metastatic liver cancer in China.

Clinical Effect of Fangfeng Tongshengsan on Post-chemoembolization Syndrome with Primary Liver Cancer or Postoperative Liver Metastases of Colorectal Cancer / 中国实验方剂学杂志

ObjectiveTo observe the effect of the Fangfeng Tongshengsan on post-chemoembolization syndrome with primary liver cancer or postoperative liver metastases of colorectal cancer. MethodSeventy-two patients suffered from post-chemoembolization syndrome after transcatheter hepatic arterial chemoembolization were randomly divided into 2 groups， including a Fangfeng Tongshengsan group and a control group， with 36 patients in each group. The patients in Fangfeng Tongshengsan group orally took the decoction for consecutive 7 d. The patients in the control group were physically cooled down with alcohol rub bath and ice pack for consecutive 7 d. Furthermore， the difference of fever， Karnofsky performance status （KPS）， pain in the liver region， nausea vomiting， constipation， and liver function between these two groups were observed. ResultCompared with the control group， Fangfeng Tongshengsan significantly relieved fever， reduced the body temperature （P<0.05）， and shortened the duration of fever （P<0.05）， indicating that Fangfeng Tongshengsan remarkably improved the KPS （P<0.05）. Meanwhile， Fangfeng Tongshengsan obviously alleviated nausea， vomiting， and constipation status and shortened the duration time compared with the control group （P<0.05）. In addition， the parameters of liver function including alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， γ-glutamyl transpeptidase （GGT）， and total bilirubin （TBIL） were significantly decreased in the Fangfeng Tongshengsan group （P<0.05）， which indicated that Fangfeng Tongshengsan alleviated liver dysfunction of patients with post-chemoembolization syndrome. ConclusionFangfeng Tongshengsan can be used to treat post-chemoembolization syndrome with primary liver cancer and postoperative liver metastases of colorectal cancer.

Expression of PD-L1 in Primary Colorectal Cancer and Its Predictive Value for Recurrence After Microwave Ablation of Liver Metastases / 肿瘤防治研究

Objective To investigate the expression of programmed death ligand 1(PD-L1) in primary tumor cells(TCs) and tumor-infiltrating immune cells(TICs) in patients with liver metastases from colorectal cancer(CRC) and determine its predictive value for recurrence after microwave ablation(MWA) of liver metastases. Methods The paraffin-embedded specimens of 28 patients with CRC liver metastasis were collected retrospectively. The expression of PD-L1 in the primary lesions was detected by immunohistochemistry, and the relationship between PD-L1 and clinical features was analyzed. Recurrence-free survival(RFS) was analyzed by Kaplan-Meier method and Log rank test. Cox proportional hazards regression model was used to analyze the factors influencing recurrence. Results The positive rates of PD-L1 in TCs and TICs in primary CRC were 14.3%(4/28) and 46.4%(13/28), respectively. PD-L1 expression in primary TICs of CRC patients with liver metastases was significantly correlated with the largest hepatic tumor diameter (P < 0.05). PD-L1 expression in primary TICs of CRC patients with liver metastasis was correlated with poor RFS after MWA (P < 0.05). PD-L1 expression in primary TICs and the largest hepatic tumor diameter > 3 cm in CRC patients with liver metastases were the risk factors for recurrence after MWA (P < 0.05). Conclusion PD-L1 expression in primary TICs of CRC patients with liver metastasis may increase the risk of recurrence after MWA for liver metastasis.

Two decades of liver resection with a multidisciplinary approach in a single institution: What has changed? Analysis of 1409 cases

Abstract Objectives: To evaluate results of patients undergoing liver resection in a single center over the past two decades with a particular look at Colorectal Liver Metastasis (CRLM) and Hepatocellular Carcinoma (HCC). Method: Patients were divided into two eras, from 2000 to 2010 (Era 1) and 2011 to 2020 (Era 2). The most frequent diagnosis was CRLM and HCC, with 738 (52.4%) and 227 (16.1%) cases respectively. An evaluation of all liver resection cases and a subgroup analysis of both CRLM and HCC were performed. Preoperative and per operative variables and long-term outcomes were evaluated. Results: 1409 liver resections were performed. In Era 2 the authors observed higher BMI, more: minimally invasive surgeries, Pringle maneuvers, and minor liver resections; and less transfusion, less ICU necessity, and shorter length of hospital stay. Severe complications were observed in 14.7% of patients, and 90-day mortality was 4.2%. Morbidity and mortality between eras were not different. From 738 CRLM resections, in Era 2 there were significantly more patients submitted to neoadjuvant chemotherapy, bilateral metastases, and smaller sizes with significantly less transfusion, the necessity of ICU, and shorter length of hospital stay. More pedicle clamping, minimally invasive surgeries, and minor resections were also observed. From 227 HCC resections, in Era 2 significantly more minimally invasive surgeries, fewer transfusions, less necessity of ICU, and shorter length of hospital stay were observed. OS was not different between eras for CRLM and HCC. Conclusions: Surgical resection in a multidisciplinary environment remains the cornerstone for the curative treatment of primary and metastatic liver tumors.

Efficacy and influencing factors of DEBIRI-TACE combined with regorafenib in the third-line or above treatment of colorectal cancer liver metastases / 国际肿瘤学杂志

Objective:To explore the efficacy and influencing factors of irinotecan-loaded CalliSpheres drug-eluting bead-transcatheter arterial chemoembolization (DEBIRI-TACE) combined with regorafenib in the third-line or above treatment of unresectable colorectal cancer liver metastases.Methods:From June 2018 to June 2020, 53 patients with unresectable colorectal cancer liver metastases admitted to Linyi Cancer Hospital of Shandong Province who had failed at least second-line systemic chemotherapy were retrospectively analyzed. The patients were divided into observation group (24 cases) and control group (29 cases) according to different treatment regimes. The control group only received regorafenib monotherapy, and the observation group received regorafenib combined with DEBIRI-TACE. According to the modified Response Evaluation Criteria in Solid Tumors, the objective response rate (ORR) and disease control rate (DCR) were evaluated, and the progression-free survival (PFS) and overall survival (OS) were estimated by Kaplan-Meier method. The Cox proportional hazards model was used to analyze the OS influencing factors in the observation group. The treatment related adverse reactions were observed.Results:After 2 months of treatment, the ORR of the observation group was 75.0% (18/24) , and the DCR was 91.7% (22/24) , both were higher than those of the control group [6.9% (2/29) and 51.7% (15/29) respectively], with statistically significant differences ( χ2=25.92, P<0.001; χ2=9.94, P=0.002) . There were no statistically significant differences in the incidences of regorafenib-related adverse reactions such as hand-foot skin reaction [62.5% (15/24) vs. 65.5% (19/29) , χ2=0.05, P=0.819], fatigue [41.7% (10/24) vs. 44.8% (13/29) , χ2=0.05, P=0.817], hypertension [29.2% (7/24) vs. 34.5% (10/29) , χ2=0.17, P=0.679], diarrhea [25.0% (6/24) vs. 27.6% (8/29) , χ2=0.04, P=0.832], hoarseness [16.7% (4/24) vs. 17.2% (5/29) , χ2=0.01, P=0.956] and proteinuria [8.3% (2/24) vs. 10.3% (3/29) , χ2=0.06, P=0.803] between the two groups. The main adverse reactions related to DEBIRI-TACE in the observation group were fever, pain, nausea and vomiting, etc., which were relieved after symptomatic treatment. No serious complications such as ectopic embolism of CalliSpheres drug eluting bead occurred. By the end of the follow-up, among the 24 patients in the observation group, the median OS of patients with simultaneous liver metastases was 12 months, and that of patients with metachronous liver metastases was 22 months, with a statistically significant difference ( χ2=4.29, P=0.026) . The median OS of patients with 3-5 liver metastases was 21 months, and that of patients with more than 5 liver metastases was 14 months, with a statistically significant difference ( χ2=3.35, P=0.040) . The median OS of Child-Pugh grade A patients was 22 months, and that of Child-Pugh grade B patients was 13 months, with a statistically significant difference ( χ2=4.22, P=0.027) . The median OS was 16 months in patients with extrahepatic metastases and 23 months in patients without extrahepatic metastases, with a statistically significant difference ( χ2=7.68, P=0.013) . Cox proportional hazards model analysis showed that simultaneous liver metastases ( HR=1.59, 95% CI: 1.02-2.47, P=0.031) and extrahepatic metastases ( HR=1.61, 95% CI: 1.29-2.01, P=0.020) were independent risk factors influencing OS of patients in the observation group. The median PFS of the observation group was 9 months, and that of the control group was 5 months, with a statistically significant difference ( χ2=7.78, P=0.005) . The median OS of the observation group was 17 months, and that of the control group was 11 months, with a statistically significant difference ( χ2=16.81, P<0.001) . Conclusion:DEBIRI-TACE combined with regorafenib is effective in the third-line or above treatment of unresectable colorectal cancer liver metastases, with tolerable adverse reactions. It is a safe and feasible treatment method. The prognosis of patients with simultaneous liver metastases or extrahepatic metastases is worse.

Clinical efficacy and adverse reactions of SBRT combined with mFOLFOXIRI and cetuximab in liver metastases after colorectal cancer surgery / 国际肿瘤学杂志

Objective:To investigate the efficacy of stereotactic body radiotherapy (SBRT) combined with modified FOLFOXIRI (mFOLFOXIRI, irinotecan, oxaliplatin, leucovorin and fluorouracil) and cetuximab in the treatment of postoperative liver metastases in patients with KRAS, BRAF and NRAS gene wild-type colorectal cancer, and to evaluate treatment-related adverse reactions.Methods:A total of 86 patients with postoperative liver metastases from colorectal cancer diagnosed in Shandong Daizhuang Hospital from January 2018 to January 2021 were selected, all of whom were KRAS, BRAF and NRAS gene wild-type. All patients were divided into control group and study group according to the random number table method, with 43 cases in each group. The patients in the control group were treated with mFOLFOXIRI and cetuximab, 14 days a cycle, for a total of 12 cycles. The patients in the study group were treated with SBRT for liver metastases on the basis of the control group. Two patients in the control group were withdrawn from the study due to intolerance of myelosuppression (grade 4), and patients in the study group were withdrawn from the study due to intolerance of 1 case of myelosuppression, 1 case of gastrointestinal reaction and 1 case of abnormal liver function (all grade 4). The efficacy, median progression-free survival (PFS), median overall survival (OS) and adverse reactions were compared between the two groups after treatment.Results:After 12 cycles of treatment, the objective response rate (ORR) and disease control rate (DCR) of the study group were 55.00% (22/40) and 80.00% (32/40) respectively, which were higher than 31.71% (13/41) and 58.54% (24/41) of the control group, with statistically significant differences ( χ2=4.48, P=0.034; χ2=4.37, P=0.037). After treatment, 14 patients (35.00%) in the study group were resectable, which was higher than 6 patients (14.63%) in the control group, with a statistically significant difference ( χ2=4.52, P=0.034). The median PFS and median OS of the study group were 9.2 months and 19.5 months respectively, which were longer than 6.5 months and 15.2 months of the control group, with statistically significant differences ( χ2=8.83, P=0.015; χ2=7.52, P=0.027). There were no significant differences in incidences of leukopenia [55.00% (22/40) vs. 46.34% (19/41), χ2=0.61, P=0.436], anemia [45.00% (18/40) vs. 39.02% (16/41), χ2=0.30, P=0.585], thrombocytopenia [37.50% (15/40) vs. 31.71% (13/41), χ2=0.30, P=0.584], nausea and vomiting [55.00% (22/40) vs. 48.78% (20/41), χ2=0.31, P=0.575], constipation and diarrhea [20.00% (8/40) vs. 17.07% (7/41), χ2=0.12, P=0.734], liver function damage [35.00% (14/40) vs. 29.27% (12/41), χ2=0.31, P=0.581], peripheral sensory neuropathy [30.00% (12/40) vs. 26.83% (11/41) ), χ2=0.10, P=0.752], acute cholinergic syndrome [12.50% (5/40) vs. 14.63% (6/41), χ2=0.08, P=0.779] and fatigue [52.50% (21/40) vs. 43.90% (18/41), χ2=0.60, P=0.439]. Conclusion:SBRT combined with mFOLFOXIRI and cetuximab is more effective than drug therapy alone in patients with liver metastases after colorectal cancer surgery, which can effectively prolong the survival period, and the adverse reactions are tolerable.

Comparison of the detection rates of colorectal cancer liver metastasis using different MRI sequences and enhanced CT / 中华肝胆外科杂志

Objective:To study the detection rates of using different MRI sequences and enhanced CT in colorectal cancer liver metastasis (CRLM).Methods:The imaging data of CRLM patients who were treated at Peking University Third Hospital from March 2018 to September 2021 were retrospectively analyzed. Sixty-six CRLM lesions with a maximum diameter ≤10 mm were selected. Different MRI sequences such as T 1 weighted imaging (T 1WI), T 2 weighted imaging (T 2WI), diffusion weighted imaging (DWI), dynamic enhanced phase of MRI (MR-Dyn), gadolinium-etoxybenzyl-diethylenetriaminepentaacetic acid (Gd-EOB-DTPA), enhanced hepatobiliary phase of MRI (HBP) and CT enhancement phase (CT-Dyn) were reviewed independently to determine whether the target lesions were detected. The pathological results were used as the gold standard. Paired chi-square test was used to compare the detection rate of CRLM in each group. Results:Among the 66 liver metastases, 15, 31, 55, 21, 56 and 20 were detected by T 1WI, T 2WI, DWI, MR-Dyn, HBP and CT-Dyn, respectively. Their detection rates were 22.7%, 47.0%, 83.3%, 31.8%, 84.8% and 30.3%, respectively. The detection rates of HBP and DWI were higher than those of T 2WI, MR-Dyn, CT-Dyn and T 1WI, respectively (all P<0.05). The detection rate of T 2WI was higher than that of MR-Dyn, CT-Dyn and T 1WI (all P<0.05). The detection efficiencies of non-contrast MRI and Gd-EOB-DTPA enhanced MRI for CRLM were highly consistent ( Kappa=0.745). Conclusions:The detection rates of HBP, DWI and T 2WI for CRLM were high. Non-contrast MRI could replace Gd-EOB-DTPA enhanced MRI for detection of large CRLM.

Exploration of the preponderant population for primary tumor resection of asymptomatic metastatic colorectal cancer / 国际肿瘤学杂志

Objective:To explore the population who benefit from primary tumor resection (PTR) of asymptomatic metastatic colorectal cancer (mCRC) .Methods:The clinicopathological data of 121 patients with asymptomatic mCRC with unresectable liver metastases treated in the First Affiliated Hospital of Yangtze University from January 2014 to January 2019 were retrospectively analyzed. Kaplan-Meier method was used to draw the survival curve accompanied with log-rank test. Cox regression model was used to analyze the prognostic factors.Results:The median overall survival (OS) of 121 mCRC patients was 20 months, and the 3- and 5-year survival rates were 34.71% and 10.74%. The median OS of PTR and non-PTR patients were 21 months and 18 months respectively, with no statistically significant difference ( χ2=0.79, P=0.375) . In 65 mCRC patients received targeted therapy, the median OS of PTR and non-PTR patients were 25 months and 28 months respectively, with no statistically significant difference ( χ2=1.65, P=0.199) . In 84 patients with mCRC of the left colon and rectum, the median OS of PTR and non-PTR patients were 24 months and 18 months respectively, with a statistically significant difference ( χ2=4.25, P=0.039) . In 37 patients with mCRC of the right colon, the median OS of PTR and non-PTR patients were 19 months and 17 months respectively, with no statistically significant difference ( χ2=0.18, P=0.675) . In 64 mCRC patients who received liver local treatment, the median OS of PTR and non-PTR patients were 36 months and 17 months respectively, with a statistically significant difference ( χ2=12.60, P<0.001) . In 57 mCRC patients who did not receive liver local treatment, the median OS of PTR and non-PTR patients were 15 months and 17 months respectively, with no significant difference ( χ2=0.58, P=0.445) . Univariate analysis showed that the location of the primary tumor ( HR=0.51, 95% CI: 0.25-0.76, P=0.025) , the degree of differentiation ( HR=1.46, 95% CI: 1.13-9.45, P=0.004) , the maximum diameter of the liver metastases ( HR=1.86, 95% CI: 1.35-4.60, P=0.012) , the level of serum carcinoembryonic antigen ( HR=3.55, 95% CI: 2.55-8.45, P<0.001) , local treatment of liver metastases ( HR=0.35, 95% CI: 0.19-0.93, P<0.001) were influencing factors for OS of asymptomatic mCRC patients with unresectable liver metastases. Multivariate analysis showed that the primary sites of the left colon and rectum ( HR=0.43, 95% CI: 0.25-0.93, P=0.039) , local treatment of liver metastases ( HR=0.78, 95% CI: 0.27-0.86, P<0.001) were independent influencing factors for OS of asymptomatic mCRC patients with unresectable liver metastases. Conclusion:Asymptomatic mCRC patients with unresectable liver metastases with primary sites of the left colon and rectum and local treatment of liver metastases can benefit from PTR.

Prognostic factors affecting the success of conversion chemotherapy in patients with unresectable liver metastases from initially colorectal cancer / 中华胃肠外科杂志

Objective: To investigate the factors affecting the success of conversion therapy in patients with initially unresectable colorectal cancer liver metastases (CRLM) in order to provide evidence-based medical evidence for formulating individualized treatment strategies for patients. Methods: A retrospective case-control study was used in this study. Clinical data of 232 patients with initially unresectable CRLM receiving first-line systemic treatment in Sun Yat-sen University Cancer Center from January 2013 to January 2020 were collected, including 98 patients of successful conversion and 134 patients of failed conversion as control. Conversion therapy scheme: 38 patients received FOLFOXIRI regimen chemotherapy (irinotecan, oxaliplatin, calcium folinate and fluorouracil), 152 patients received FOLFOX regimen (oxaliplatin, calcium folinate and fluorouracil), 19 patients received FOLRIRI regimen (irinotecan, calcium folinate and fluorouracil), 23 patients received systemic chemotherapy combined with fluorouridine hepatic artery infusion chemotherapy; 168 patients received targeted therapy, including 68 of bevacizumab and 100 of cetuximab. Logistics analysis was used to compare the factors affecting the success of conversion therapy. The Kaplan-Meier method was used to calculate progression-free survival (PFS), and the Log-rank test was used for survival comparison. Results: Among 232 patients, 98 patients had successful conversions and 134 patients had failed conversions with a successful conversion rate of 42.2%, meanwhile 30 patients underwent simple hepatectomy and 68 underwent hepatectomy combined with intraoperative radiofrequency ablation. After first-line chemotherapy, 111 patients (47.8%) were partial remission, 57 patients (24.6%) were stable disease, and 64 patients (27.6%) were progression disease. During the median follow-up of 18.8 (1.0-87.9) months, 148 patients were dead or with tumor progression. The median PFS time of patients with successful conversion was longer than that of patients with failed conversion (31.0 months vs. 9.9 months, P<0.001). Univariate analysis found that the bilobar distribution of liver tumors (P=0.003), elevated baseline carcinoembryonic antigen (CEA) levels (P=0.024), tumor invasion of the portal vein (P=0.001), number of metastatic tumor>8 (P<0.001), non-FOLFOXIRI (P=0.005), and no targeted therapy (P=0.038) were high risk factors for the failed conversion therapy. The results of multivariate logistics analysis indicated that the number of metastatic tumor >8 (OR=2.422, 95%CI: 1.291-4.544, P=0.006), portal vein invasion (OR=2.727, 95%CI: 1.237-4.170, P=0.008) were the independent risk factors for failed conversion therapy, while FOLFOXIRI regimen (OR=0.300, 95%CI: 0.135-0.666, P=0.003) and targeted drugs (OR=0.411, 95%CI: 0.209-0.809, P=0.010) were independent protective factors for successful conversion therapy. Conclusions: The number of metastatic tumor and portal vein invasion are key factors that affect the outcomes of conversion therapy for initially unresectable CRLM. If a patient can tolerate chemotherapy, a combination program of three-drug and targeted therapy is preferred for the active conversion therapy.

Hepatectomía en dos tiempos por metástasis hepáticas bilobares de origen colorrectal: reporte de un caso / Two-stage hepatectomy for bilobar colorectal liver metastases: case report / Hepatectomia em dois estágios para metástases hepáticas bilobares de origem colorretal: relato de um caso

La mitad de los pacientes con cáncer de origen colorrectal desarrollan metástasis hepáticas durante el curso de su enfermedad y de esas el 80% son irresecables. La resecabilidad se define no por la extensión de la hepatectomía, sino por la función del hígado remanente, por lo que para pacientes con ciertos factores favorables se pueden realizar técnicas de remodelación hepática para aumentar el volumen del hígado remanente para que este sea suficiente. La hepatectomía en dos tiempos se basa en procedimientos secuenciales que buscan tratar metástasis hepáticas colorrectales consideradas inicialmente irresecables, logrando la resección completa de las mismas dejando un remanente hepático funcionante suficiente, lo cual no sería posible en un solo acto quirúrgico. El objetivo de este trabajo es presentar el caso clínico de un paciente portador de metástasis hepáticas sincrónicas de origen colorrectal irresecables, que luego de una quimioterapia de conversión, con el fin de aumentar el futuro remanente hepático y evitar falla hepática postoperatoria y realizar una resección oncológica, fue sometido a una hepatectomía en dos tiempos, técnica utilizada con baja frecuencia en nuestro medio, destacando una evolución favorable, con marcadores tumorales en valores normales y sin evidencia imagenológica de recaída local ni sistémica.

Half of colorectal cancer patients develop liver metastases during the course of their disease, 80% of which are unresectable. Resectability is defined not by the extent of the hepatectomy, but by the function of the liver remnant. Therefore, for patients with certain factors, liver remodeling techniques can be performed to increase volume of the remaining liver so that it is sufficient. Two-stage hepatectomy is performed on colorectal liver metastases which are initially considered unresectable in one stage resection procedures, in which sequential procedures are performed in order to achieve complete resection and preserve a sufficient functioning liver remnant. The objective of this paper is to present the case of a patient with unresectable synchronous colorectal liver metastases, in which after conversion chemotherapy, in order to increase the future liver remnant, avoid postoperative liver failure and perform an oncological resection underwent a two-stage hepatectomy, a technique used with low frequency in our setting, highlighting a favorable evolution, with tumor markers in normal values and without imaging evidence of local or systemic relapse.

Metade dos pacientes com câncer colorretal desenvolve metástases hepáticas durante o curso da doença e, desses, 80% são irressecáveis. A ressecabilidade é definida não pela extensão da hepatectomia, mas pela função do fígado remanescente; portanto, para pacientes com certos fatores favoráveis, técnicas de remodelação hepática podem ser realizadas para aumentar o volume do fígado remanescente de forma que seja suficiente. A hepatectomia em dois estágios é baseada em procedimentos sequenciais que buscam tratar metástases hepáticas colorretais inicialmente consideradas irressecáveis, obtendo ressecção completa, deixando um remanescente hepático funcional suficiente, o que não seria possível em um único ato cirúrgico. O objetivo deste trabalho é apresentar o caso clínico de um paciente com metástases hepáticas sincrônicas irressecáveis ​​de origem colorretal, que após quimioterapia de conversão, com o objetivo de aumentar o futuro remanescente hepático e evitar insuficiência hepática pós-operatória e realizar uma ressecção oncológica, foi submetido a dois Hepatectomia em estágio, técnica utilizada com baixa frequência em nosso meio, evidenciando evolução favorável, com marcadores tumorais em valores normais e sem evidências de imagem de recidiva local ou sistêmica.

China guideline for diagnosis and comprehensive treatment of colorectal liver metastases (version 2020) / 中华胃肠外科杂志

The liver is the most common anatomical site for hematogenous metastases of colorectal cancer, and colorectal liver metastasis is one of the most difficult and challenging situations in the treatment of colorectal cancer. In order to improve the diagnosis and comprehensive treatment in China, the Guidelines have been edited and revised for several times since 2008, including the overall evaluation, personalized treatment goals and comprehensive treatments, to prevent the occurrence of liver metastases, improve the resection rate of liver metastases and survival. The revised Guideline version 2020 includes the diagnosis and follow-up, prevention, multidisciplinary team (MDT), surgery and local ablative treatment, neoadjuvant and adjuvant therapy, and comprehensive treatment, with state-of-the-art experience and findings, detailed content, and strong operability.

Current status and prospects in surgical treatment of pancreatic neuroendocrine tumor with liver metastases / 中华内分泌外科杂志

Pancreatic neuroendocrine tumor (pNET) is a heterogeneous group of neoplasms that vary in their clinical presentation, biological behavior and prognosis. The most common site of metastasis is the liver. Surgical resection of both primary tumor and liver metastases is thought to have the best long-term outcomes by achieving a radical resection. The role of primary tumor resection in the setting of unresectable metastatic disease is controversial; However, more and more studies demonstrate an active cytoreductive surgery will benefit patients with a reasonable preoperative evaluation. For patients who are not surgical candidates, neoadjuvant therapy is attempted to find if it would downstage the tumor to regain the opportunity of R0 resection. Cytotoxic chemotherapy, targeted therapy, and PRRT present good treatment prospects, and further research is still needed. With multidisciplinary treatment, individualized protocol should provide patients a better treatment results.

Prognosis-related Factors of Colorectal Cancer Patients with Positive PD-L1 Expression in Liver Metastases After Hepatectomy / 肿瘤防治研究

Objective To evaluate the prognosis-related factors of colorectal cancer patients with positive PD-L1 expression in liver metastases after hepatectomy. Methods We reviewed retrospectively the clinical data of 68 colorectal cancer patients with positive PD-L1 expression in liver metastases receiving personalized comprehensive treatment which was mainly consisted of surgical resection. We observed the results and prognosis after surgical resection and analyzed related factors. Results Univariate analysis showed that no radiotherapy, N stage, RAS mutation status, T stage, dMMR, Duck stage, disease free interval from primary to metastases≤12 months and largest hepatic tumor diameter > 5 cm had obvious significance (all P < 0.05). Multivariate logistic analysis regression revealed that without dMMR (P=0.012), Duck A stage (P=0.000), disease free interval from primary to metastases > 12 months (P=0.020) and largest hepatic tumor diameter < 5 cm (P=0.006) were independent protective factors for the prognosis of colorectal cancer patients with positive PD-L1 expression in liver metastases after surgical resection. Conclusion Personalized comprehensive treatment which is mainly consisted of surgical resection still has a good effect on colorectal cancer patients with positive PD-L1 expression in liver metastases after hepatectomy. Without dMMR, Duck A stage, disease free interval from primary to metastases > 12 months and largest hepatic tumor diameter ≤5cm are independent protective factors for patients' prognosis.

Clinical research progress on disappearing colorectal liver metastases / 中华胃肠外科杂志

Colorectal cancer is currently one of the most common digestive system tumors, and the liver is the most common metastatic site of colorectal cancer. In recent years, with the continuous development of the multidisciplinary treatment for colorectal cancer patients, there are quite a few cases of disappearing liver metastases (DLM) after receiving preoperative chemotherapy (or combined targeted drug therapy), and the diagnosis and treatment of DLM is currently still a very challenging and controversial topic. This article sorts out the related researches on DLM in recent years, mainly including the following 4 aspects: (1) The factors associated with DLM, including the size and number of liver metastases, chemotherapy regimens and cycles, targeted therapy drugs, and the pattern of liver metastases, Ras/Braf status and the location of the primary lesion. (2) The relationship between DLM and true complete response (pathological complete response and persistent clinical complete response), and the related predictive factors of pathological complete response. (3) Clinical evaluation of DLM: preoperative evaluation includes ultrasound, CT, MRI, and PET, while intraoperative evaluation includes intraoperative exploration, intraoperative ultrasound, and augmented reality. (4) DLM treatment strategies, including surgical treatment, local treatment, non-surgical treatment and individualized treatment.

Advances and challenges in neoadjuvant treatment for colorectal cancer liver metastasis / 中华胃肠外科杂志

Liver metastasis is the leading cause of death in patients with colorectal cancer. Since surgical resection alone has a high postoperative recurrence rate, neoadjuvant therapy as an important means is widely applied in order to reduce recurrence and improve survival. Progress has been achieved in many aspects of neoadjuvant therapy in colorectal cancer liver metastasis, such as eligible patients selection, optimal regimens and courses of chemotherapy. However, controversies still remain regarding the standards of resectability of lesions and the application of targeted drugs. Individualized treatments could be developed based on multidisciplinary teamwork to achieve the goal of 'resources integration and treatment stratification'.

Comparative study on prognosis of neoadjuvant chemotherapy followed by hepatic surgery versus upfront surgery in patients with synchronous colorectal liver metastasis / 中华胃肠外科杂志

Objective: To compare the survival outcome in patients with synchronous colorectal cancer liver metastasis receiving neoadjuvant chemotherapy followed by hepatic surgery versus upfront surgery strategies. Methods: A retrospective cohort study was carried out. Data of patients undergoing surgery at the Department of Hepatopancreatobiliary Surgery Unit I of Peking University Cancer Hospital from January 2008 to December 2018 for initially resectable synchronous colorectal liver metastasis were retrospectively collected. A total of 282 cases were enrolled, including 244 in the neoadjuvant chemotherapy group, 38 in the upfront surgery first group. The overall survival (OS) and progression-free survival (PFS) of the two groups were compared. A propensity score risk adjustment was used to eliminate potential bias between groups, and the covariates including sex, age, location of primary tumor, T stage, clinical risk score (CRS), RAS gene status, adjuvant chemotherapy, and resection margin status were included for adjustment. Results: In the neoadjuvant chemotherapy group, 244 cases received 4 (1-15) cycles of chemotherapy before hepatic resection, among whom 207 cases received oxaliplatin-based regimens, 37 cases received irinotecan-based regimens, and 90 cases received combined targeted agents in the first line treatment. The median follow-up time was 30 (5-134) months, and loss of follow-up was 1%. Before adjustment, Kaplan-Meier survival analysis showed that the 1-year and 3-year OS rates in the neoadjuvant chemotherapy group (95.1% and 66.4%) were better than those in the upfront surgery first group (94.7% and 51.5%, P=0.026); 1-year and 3-year PFS rates in neoadjuvant chemotherapy group (51.0% and 23.4%) were also better than those in surgery first group (39.5% and 11.5%, P=0.039). After propensity score risk adjustment, Cox multivariate analysis indicated that neoadjuvant chemotherapy was an independent protective factor of PFS (HR=0.664, 95% CI: 0.449-0.982, P=0.040), however, neoadjuvant chemotherapy was not an independent protective factor of OS (HR=0.651, 95% CI: 0.393-1.079, P=0.096). Subgroup analysis showed that the 1-year and 3-year OS rates in the patients with response to the first line treatment (194, including complete remission, partial remission and reduction but not partial remission) (96.9% and 67.1%) were better than those in the upfront surgery group (94.7% and 51.5%, P=0.026) after adjustment. However, the 1-year and 3-year OS rates in the patients without response to the first line treatment (50, including tumor progression or enlargement) were 90.0% and 63.3%, respectively, which were not significantly different with 94.7% and 51.5% in the upfront surgery group (P=0.310) after adjustment. Conclusions: For patients with resectable synchronous colorectal cancer liver metastasis, liver resection after neoadjuvant chemotherapy can provide longer PFS than upfront surgery. Although the whole OS benefit is not significant, patients with effective neoadjuvant first-line chemotherapy have better OS than those undergoing upfront surgery.

Research progress of conversion therapy in colorectal cancer liver metastases / 中华胃肠外科杂志

The probability of developing liver metastases in patients with colorectal cancer is 40%-50%. Liver metastases remain an important adverse factor affecting long-term prognosis of colorectal cancer patients. Surgical resection of liver metastases is the only potentially curative treatment option. After comprehensive treatment, initially unresectable liver metastases might be converted to resectable tumors. This concept is known as conversion therapy. In this review, research status of conversion therapy in colorectal cancer liver metastases was summarized, providing updated concept of resectability, discussions on the assessment of tumor response and timing of operation, debates on the influence on tumor sidedness, and latest advancement in the treatment strategy of conversion therapy. Through analyzing existing problems, we hope to offer insights into possible progress in the future and provide references for the development of clinical practice.