Considering extended right lobe grafts as major extended donor criteria in liver transplantation is justified

The outcomes of split-liver transplantation are controversial. This study compared outcomes and morbidity after extended right lobe liver transplantation (ERLT) and whole liver transplantation (WLT) in adults. MEDLINE and Web of Science databases were searched systematically and unrestrictedly for studies on ERLT and its impact on graft and patient survival, and postoperative complications. Graft loss and patient mortality odds ratios (OR) and 95% confidence intervals (CI) were assessed by meta-analyses using Mantel–Haenszel tests with a random-effects model. Vascular and biliary complications, primary nonfunction, 3-month, 1-, and 3-year graft and patient survival, and retransplantation after ERLT and WLT were analyzed. The literature search yielded 10 594 articles. After exclusion, 22 studies (n = 75 799 adult transplant patients) were included in the analysis. ERLT was associated with lower 3-month (OR = 1.43, 95% CI = 1.09–1.89, P = 0.01), 1-year (OR = 1.46, 95% CI = 1.08–1.97, P = 0.01), and 3-year (OR = 1.37, 95% CI = 1.01–1.84, P = 0.04) graft survival. WL grafts were less associated with retransplantation (OR = 0.57; 95% CI = 0.41–0.80; P < 0.01), vascular complications (OR = 0.53, 95% CI = 0.38–0.74, P < 0.01) and biliary complications (OR = 0.67; 95% CI = 0.47–0.95; P = 0.03). Considering ERLT as major Extended Donor Criteria is justified because ERL grafts are associated with vasculobiliary complications and the need for retransplantation, and have a negative influence on graft survival.     

The difficulty in defining extended donor criteria for liver grafts: the Eurotransplant experience

Donor criteria for liver grafts have been expanded because of organ shortage. Currently, no exact definitions for extended donor grafts have been established. The aim of this study was to analyze the impact of donor‐specific risk factors, independent of recipient characteristics. In collaboration with Eurotransplant and European Liver Transplant Register, solely donor‐specific parameters were correlated with 1‐year survival following liver transplantation. Analyses of 4701 donors between 2000 and 2005 resulted in the development of a nomogram to estimate graft survival for available grafts. Predictions by nomogram were compared to those by Donor Risk Index (DRI). In the multivariate analysis, cold ischemic time (CIT), highest sodium, cause of donor death, γ‐glutamyl transferase (γ‐GT), and donor sex (female) were statistically significant factors for 3 months; CIT, γ‐GT, and cause of donor death for 12‐month survival. The median DRI of this study population was 1.45 (Q1: 1.17; Q3: 1.67). The agreement between the nomogram and DRI was weak (kappa = 0.23). Several donor‐specific risk factors were identified for early survival after liver transplantation. The provided nomogram will support quick organ quality assessment. Nevertheless, this study showed the difficulties of determining an exact definition of extended criteria donors.     

Perioperative chemotherapy and hepatic resection for resectable colorectal liver metastases

The role of perioperative chemotherapy in the management of initially resectable colorectal liver metastases (CRLM) is still unclear. The EPOC trial [the European Organization for Research and Treatment of Cancer (EORTC) 40983] is an important study that declares perioperative chemotherapy as the standard of care for patients with resectable CRLM, and the strategy is widely accepted in western countries. Compared with surgery alone, perioperative FOLFOX therapy significantly increased progression-free survival (PFS) in eligible patients or those with resected CRLM. Overall survival (OS) data from the EPOC trial were recently published in The Lancet Oncology, 2013. Here, we discussed the findings and recommendations from the EORTC 40983 trial.     

Liver transplantation for colorectal liver metastases: revisiting the concept

Liver transplantation (Lt) for colorectal cancer (CRC) liver metastases is no more considered due to the poor outcome observed up to the 1990s. According to the European Liver Transplant Registry (ELTR), 1‐ and 5‐year patient survival following Lt for CRC liver metastases performed prior to 1995 was 62% and 18%, respectively. However, 44% of graft loss or patient deaths were not related to tumor recurrence. Over the last 20 years there has been dramatic progress in patient survival after Lt, thus it could be anticipated that survival after Lt for CRC secondaries today would exceed from far, the outcome of the past experience. By utilizing new imaging techniques for proper patient selection, modern chemotherapy and aggressive multimodal treatment against metastases, long term survivors and even cure could be expected. Preliminary data from a pilot study show an overall survival rate of 94% after a median follow up of 25 months. While long term survival after the first Lt is 80% all indications confounded, 5‐year survival after repeat Lt is no more than 50% to 55%. If patients transplanted for CRC secondaries can reach the latter survival rate, it could be difficult to discriminate them in the liver allocation system and live donation could be an option.     

结直肠癌肝脏转移的基础研究进展

肝转移是结直肠肿瘤患者预后不良的独立危险因素,本文就国外近5年来对肝转移机制研究的状况作出大体的总结:研究发现肿瘤细胞对肝血窦特异性的黏附是导致转移发生的一个重要因素.转移的过程大体可分为:脱落、黏附、入侵、生存、增生.在肝转移发生过程中,肝脏的非实质细胞与肿瘤细胞相互作用促使肿瘤生长.缺氧、炎症、免疫抑制是肿瘤微环境的特点,微环境中的各种细胞因子在肿瘤进展中发挥不可忽视的作用.     

Impact of liver-directed therapy in colorectal cancer liver metastases

Background

There is a paucity of data on the current management and outcomes of liver-directed therapy (LDT) in older patients presenting with stage IV colorectal cancer (CRC). The aim of the study was to evaluate treatment patterns and outcomes in use of LDT in the setting of improved chemotherapy.

Methods

We used Cancer Registry and linked Medicare claims to identify patients aged ≥66 y undergoing surgical resection of the primary tumor and chemotherapy after presenting with stage IV CRC (2001–2007). LDT was defined as liver resection and/or ablation-embolization.

Results

We identified 5500 patients. LDT was used in 34.9% of patients; liver resection was performed in 1686 patients (30.7%), and ablation-embolization in 554 patients (10.1%), with 322 patients having both resection and ablation-embolization. Use of LDT was negatively associated with increasing year of diagnosis (odds ratio [OR] = 0.96, 95% confidence interval [CI] 0.93–0.99), age >85 y (OR = 0.61, 95% CI 0.45–0.82), and poor tumor differentiation (OR = 0.73, 95% CI 0.64–0.83). LDT was associated with improved survival (median 28.4 versus 21.1 mo, P < 0.0001); however, survival improved for all patients over time. We found a significant interaction between LDT and period of diagnosis and noted a greater survival improvement with LDT for those diagnosed in the late (2005–2007) period.

Conclusions

Older patients with stage IV CRC are experiencing improved survival over time, independent of age, comorbidity, and use of LDT. However, many older patients deemed to be appropriate candidates for resection of the primary tumor and receipt of systemic chemotherapy did not receive LDT. Our data suggest that improved patient selection may be positively impacting outcomes. Early referral and optimal selection of patients for LDT has the potential to further improve survival in older patients presenting with advanced colorectal cancer.     

Synchronous resection of colorectal cancer and liver metastases: comparative views of colorectal and liver surgeons

Aim The optimal management of patients presenting with colorectal cancer and synchronous liver metastases is controversial. This survey was intended to summarize the opinions of UK colorectal and liver surgeons on the specific issues pertaining to synchronous resection. Method A validated electronic survey was sent to the consultant members of the Association of Coloproctology of Great Britain and Ireland (ACPGBI) and the Association of Upper Gastrointestinal Surgeons (AUGIS). The questions were structured to allow direct comparison between the two groups of the responses obtained. Results Four hundred and twenty‐four specialist colorectal surgeons and 52 specialist hepatobiliary surgeons were identified from the register of their respective associations. Responses were obtained from 133 (31%) colorectal and 22 (42%) liver surgeons. A majority of both groups of surgeons felt that synchronous resection was a valid therapeutic option. A majority of both groups believed that synchronous resection was justified despite the options of laparoscopic surgery and enhanced recovery programmes for each discipline. Agreed possible advantages of synchronous resections were: a decrease in the overall length of hospital stay, cost and patient anxiety. The major concern about synchronous resections was an excessive overall physiological insult. Specific scenarios indicated that synchronous resection was favoured for major/complex major colorectal resection with minor liver resection or most colorectal resections not involving an anastomosis with either a minor or major liver resection. Conclusion Although significant concerns relating to synchronous resection remain amongst colorectal and liver surgeons, a majority of them felt that synchronous resections could be offered to appropriately selected patients.     

大肠癌肝转移动物模型的研究进展

肝脏是大肠癌转移的最常见器官.为更好地研究大肠癌肝转移,建立和选择合适的大肠癌肝转移模型十分重要.在此就大肠癌肝转移模型:原位植入模型,经脾接种癌细胞,门静脉内注射,直接将癌细胞种植到肝脏的相关研究进展进行综述.     

Safety of dual kidney transplantation compared to single kidney transplantation from expanded criteria donors: a single center cohort study of 39 recipients

Our objective was to compare the outcomes of dual kidney transplanataion (DKT) to single kidney transplantation (SKT) performed with grafts from expanded criteria donors (ECD) in recipients ≥65 years, focusing on surgical complications. All kidney transplantations (KT) performed between 2006 and 2014 in our institution were analysed. DKT was indicated according to the criteria of the French national Agence de la Biomedecine. Thirty‐nine DKT and 155 SKT were included, with a median follow‐up of 36 and 26.5 months, respectively. The rate of early surgical revisions was not significantly higher after DKT (23.1% vs 15.5% (P = 0.2593)) but more venous graft thromboses (12.8% vs 3.2% (P = 0.02)) were reported. The glomerular filtration rate (GFR) 24 months after KT was significantly higher after DKT (45.0 ± 16.3 vs 39.8 ± 13.8 ml/min/1.73m²; P = 0.04) and allowed shorter waiting time without a significant increased risk of surgical revision, excepted for venous graft thrombosis, more frequent after DKT. Graft survivals were not significantly different and GFR was higher after DKT. DKT seems to remain an appropriate strategy to address the growing graft shortage in elderly patients.     

The incidence and outcome of brain metastases after liver resection for colorectal cancer metastases

Aim Brain metastases from colorectal cancer are rare, with an incidence of 0.6–4%. The risk and outcome of brain metastases after hepatic and pulmonary metastasectomy have not been previously described. This study aimed to determine the incidence, predictive factors, treatment and survival of patients developing colorectal brain metastases, who had previously undergone resection of hepatic metastases. Method A retrospective review was carried out of a prospectively maintained database of patients undergoing liver resection for colorectal metastases. Results Fifty‐two (4.0%) of 1304 patients were diagnosed with brain metastases. The annual incidence rate was 1.03% per person‐year. In the majority of cases brain metastases were found as part of multifocal disease. Median survival was 3.2 months (95% CI: 2.3–4.1), but was best for six patients treated with potentially curative resection [median survival = 13.2 (range, 4.9–32.1) months]. Multivariate analysis showed that a lymph node‐positive primary tumour [hazard ratio (HR) = 2.7, 95% CI: 1.8–6.19; P = 0.019], large liver metastases (> 6 cm) [HR = 2.23, 95% CI: 1.19–2.33; P = 0.012] and recurrent intrahepatic and extrahepatic disease [HR = 2.11, 95% CI: 1.2–4.62; P = 0.013] were independent predictors for the development of brain metastases. Conclusion The annual risk of developing brain metastases following liver resection for colorectal metastases is low, but highest for patients presenting with a Dukes’ C primary tumour, large liver metastases or who subsequently develop disseminated disease. The overall survival from colorectal brain metastases is poor, but resection with curative intent offers patients their best chance of medium‐term survival.     

Oncological benefit of complete metastasectomy for simultaneous colorectal liver and lung metastases

BackgroundThe oncological benefit of complete metastasectomy for simultaneous colorectal liver and lung metastases (SLLM) have not been fully investigated.MethodsPatients undergoing initial hepatectomy for colorectal liver metastases (CLM) from 2005 to 2016 were divided into three groups: patients with isolated CLM undergoing complete resection (Group1, n = 317), SLLM undergoing complete metastasectomy (Group2, n = 33), and SLLM undergoing complete hepatectomy but incomplete lung resection (Group3, n = 20). A staged strategy (hepatectomy followed by lung resection) without interval chemotherapy was mainly applied for SLLM.ResultsThe 5-year overall survival rate of Group2 was significantly better than that of Group3 (71.7% vs. 10.2%, P < 0.001) and similar to that of Group1 (63.9%, P = 0.779). The 5-year disease-free survival rate was significantly worse in Group2 than Group1 (15.7% vs. 29.0%, P = 0.035). On multivariable analysis, CEA>200 ng/ml was the sole predictor of incomplete resection of lung metastases (odds ratio, 13.7; 95% confidence interval, 1.30–145; P = 0.011).ConclusionsThe prognosis in patients with SLLM who achieve complete metastasectomy is acceptable and might be improved by appropriate selection based on operative indications.     

The number of lung transplants can be safely doubled using extended criteria donors; A single‐center review

Relaxing the standard lung donor criteria may significantly increase the reported 15% organ yield but post‐transplant recipient outcome should be carefully monitored. Charts from all consecutive deceased organ donors within our hospital network were reviewed over a 2‐year period. Reasons for lung refusals and number of lungs transplanted were analysed. Hospital outcome including early recipient survival was compared between standard‐ and extended criteria donors. Out of 283 referrals, 164 (58%) qualified as donor of any organ. The majority (65.9%) of these effective donors were declined for lung donation because of chest X‐ray abnormalities (20%), age >70 years (13%), poor oxygenation (10%), or aspiration (9%). Out of 56 (34.1%) accepted lung donors, 50 transplants were performed at our center, 23 from standard criteria donors versus 27 from extended criteria donors. There were no significant differences in hospital outcome and in early survival between lung recipients from both donor groups. Lung acceptance rate (34.1%) in our donor network is 10–20% higher than reported figures. The number of lung transplants in our center doubled by accepting extended criteria donors. This policy did not negatively influence our results after lung transplantation.     

The timing of liver resection in patients with colorectal cancer and synchronous liver metastases: a population‐based study of current practice and survival

Aim

There is uncertainty regarding the optimal sequence of surgery for patients with colorectal cancer (CRC) and synchronous liver metastases. This study was designed to describe temporal trends and inter‐hospital variation in surgical strategy, and to compare long‐term survival in a propensity score‐matched analysis.

Method

The National Bowel Cancer Audit dataset was used to identify patients diagnosed with primary CRC between 1 January 2010 and 31 December 2015 who underwent CRC resection in the English National Health Service. Hospital Episode Statistics data were used to identify those with synchronous liver‐limited metastases who underwent liver resection. Survival outcomes of propensity score‐matched groups were compared.

Results

Of 1830 patients, 270 (14.8%) underwent a liver‐first approach, 259 (14.2%) a simultaneous approach and 1301 (71.1%) a bowel‐first approach. The proportion of patients undergoing either a liver‐first or simultaneous approach increased over the study period from 26.8% in 2010 to 35.6% in 2015 (P < 0.001). There was wide variation in surgical approach according to hospital trust of diagnosis. There was no evidence of a difference in 4‐year survival between the propensity score‐matched cohorts according to surgical strategy: bowel first vs simultaneous [hazard ratio (HR) 0.92 (95% CI: 0.80–1.06)] or bowel first vs liver first [HR 0.99 (95% CI: 0.82–1.19)].

Conclusion

There is evidence of wide variation in surgical strategy in dealing with CRC and synchronous liver metastases. In selected patients, the simultaneous and liver‐first strategies have comparable long‐term survival to the bowel‐first approach.     

Borderline resectable for colorectal liver metastases: Present status and future perspective

Surgical resection for colorectal liver metastases (CRLM) may offer the best opportunity to improve prognosis. However, only about 20% of CRLM cases are indicated for resection at the time of diagnosis (initially resectable), and the remaining cases are treated as unresectable (initially unresectable). Thanks to recent remarkable developments in chemotherapy, interventional radiology, and surgical techniques, the resectability of CRLM is expanding. However, some metastases are technically resectable but oncologically questionable for upfront surgery. In pancreatic cancer, such cases are categorized as “borderline resectable”, and their definition and treatment strategies are explicit. However, in CRLM, although various poor prognosis factors have been identified in previous reports, no clear definition or treatment strategy for borderline resectable has yet been established. Since the efficacy of hepatectomy for CRLM was reported in the 1970s, multidisciplinary treatment for unresectable cases has improved resectability and prognosis, and clarifying the definition and treatment strategy of borderline resectable CRLM should yield further improvement in prognosis. This review outlines the present status and the future perspective for borderline resectable CRLM, based on previous studies.     

Potential use of Doppler perfusion index in detection of occult liver metastases from colorectal cancer

Many clinical and preclinical studies demonstrated that measurements of liver hemodynamic [Doppler perfusion index (DPI)] may be used to accurately diagnose and predict liver metastases from primary colorectal cancer in a research setting. However, Doppler measurements have some serious limitations when applied to general population. Ultrasound is very operator-dependent, and requires skilled examiners. Also, many conditions may limit the use of Doppler ultrasound and ultrasound in general, such as the presence of air in digestive tract, cardiac arrhythmias, vascular anomalies, obesity and other conditions. Therefore, in spite of the results from clinical studies, its value may be limited in everyday practice. On the contrary, scientific research of the DPI in detection of liver metastases is of great importance, since current research speaks strongly for the presence of systemic vasoactive substance responsible for observed hemodynamic changes. Identification of such a systemic vasoactive substance may lead to the development of a simple and reproducible laboratory test that may reliably identify the presence of occult liver metastases and therefore increase the success of adjuvant chemotherapy through better selection of patients. Further research in this subject is therefore of great importance.     

The management of perioperative nutrition in patients with end stage liver disease undergoing liver transplantation

Malnutrition is found in almost 100% of patients with end stage liver disease (ESLD) awaiting transplantation and malnutrition before transplantation leads to higher rates of post-transplant complications and worse graft survival outcomes. Reasons for protein energy malnutrition include several metabolic alterations such as inadequate intake, malabsorption, and overloaded expenditure. And also, stress from surgery, gastrointestinal reperfusion injury, immunosuppressive therapy and corticosteriods use lead to delayed bowl function recovery and disorder of nutrients absorption. In the pretransplant phase, nutritional goals include optimization of nutritional status and treatment of nutrition-related symptoms induced by hepatic decompensation. During the acute post-transplant phase, adequate nutrition is required to help support metabolic demands, replenish lost stores, prevent infection, arrive at a new immunologic balance, and promote overall recovery. In a word, it is extremely important to identify and correct nutritional deficiencies in this population and provide an adequate nutritional support during all phases of liver transplantation (LT). This study review focuses on prevalence, nutrition support, evaluation, and management of perioperative nutrition disorder in patients with ESLD undergoing LT.