Down-staging depth score to predict outcomes in locally advanced rectal cancer achieving ypl stage after neoadjuvant chemo-radiotherapy versus de novo stage pl cohort:A propensity score-matched analysis

Objective：Prognosis of patients with locally advanced rectal cancer（LARC）but achieving yp T1–2N0 stage after neoadjuvant concurrent chemo-radiotherapy（CRT）has been shown to be favorable.This study aims to determine whether the long-term outcome of yp T1–2N0 cases can be comparable to that of p T1–2N0 cohort that received definitive surgery for early disease.Method：From January 2008 to December 2013,449 consecutive patients with rectal cancer were treated and their outcome maintained in a database.Patients with LARC underwent total mesorectal excision（TME）surgery at4–8 weeks after completion of CRT,and those achieving stage yp I were identified as a group.As a comparison,stage p I group pertains to patients whose initially limited disease was not upstaged after TME surgery alone.After propensity score matching（PSM）,comparisons of local regional control（LC）,distant metastasis-free survival（DMFS）,disease-free survival（DFS）and overall survival（OS）were performed using Kaplan-Meier analysis and log-rank test between yp I and p I groups.Down-staging depth score（DDS）,a novel method of evaluating CRT response,was used for subset analysis.Results：Of the 449 patients,168 matched cases were generated for analysis.Five-year LC,DMFS,DFS and OS for stage p I vs.yp I groups were 96.7%vs.96.4%（P=0.796）,92.7%vs.73.6%（P=0.025）,91.2%vs.73.6%（P=0.080）and 93.1%vs.72.3%（P=0.040）,respectively.In the DDS-favorable subset of the yp I group,LC,DMFS,DFS and OS resulted in no significant differences in comparison with the p I group（P=0.384,0.368,0.277 and0.458,respectively）.Conclusions：LC was comparable in both groups;however,distant metastasis developed more frequently in down-staged LARC than de novo early stage cases,reflecting the need to improve the efficacy of systemic treatment despite excellent pathologic response.DDS can be an indicator to identify a subset of the yp I group whose longterm oncologic outcomes are as good as those of stage p I cohort.

Outcomes of loco-regional therapy for down-staging of hepatocellular carcinoma prior to liver transplantation

BACKGROUND: The number of loco-regional therapies (LRTs) for hepatocellular carcinoma (HCC) has increased dramatically during the past decade. Many patients with HCC who were beyond the Milan criteria were allowed to receive a liver transplantation (LT) once the HCC was successfully down-staged. This retrospective study aimed to analyze the outcomes of LRTs prior to LT in patients with HCC beyond the Milan criteria. METHODS: We analyzed 56 patients treated from June 2006 to March 2010: 22 met the Milan criteria (T1+T2, 39.3%), 16 had T3 tumors (28.6%), and 11 had T4a tumors (19.6%), while 7 were suspected of tumor vascular invasion (T4b, 12.5%). All patients underwent preoperative LRTs, including transcatheter arterial chemoembolization, radiofrequency ablation, percutaneous ethanol injection, liver resection, and/or microwave coagulation therapy. The number of the patients who were successfully down-staged before LT, the types of LRTs used before LT, and their outcomes after LT were recorded. RESULTS: Eleven patients had necrotic tumors (pT0, 19.6%); 6 had pT1 tumors (10.7%), 22 had pT2 tumors (39.3%), 6 had pT3 tumors (10.7%), 5 had pT4a tumors (8.9%), and 6 had pT4b tumors (10.7%). The histopathologic tumors of 39 patients (69.6%) were down-staged and met the established Milan criteria (pT0-2). Imaging-proven under-staging was present in 5 HCC patients (8.9%) who had tumors involving the intrahepatic venous system. Twenty-three patients (41.1%) had stable HCC and 10 (17.9%) died. The 1-, 3- and 4-year survival rates were 96%, 73% and 61%, respectively, with a mean survival time of 22.29±1.63 months. Six patients died of tumorrecurrence. The 1-, 3- and 4-year recurrence-free survival (RFS) rates were 88%, 75% and 66%, respectively. The 3-year RFS of patients with pT0-2 tumors was 82%, which was markedly greater than that of patients with pT3 tumors (63%, P=0.018) or pT4 tumors (17%, P=0.000). Although the 3-year RFS of patients with pT3 tumors was greater than that of patients with pT4 tumors, the difference was not significant. CONCLUSIONS: Successful down-staging of HCCs can be achieved in the majority of carefully selected patients by LRTs. Importantly, patients who are successfully down-staged and undergo LT may have a higher RFS rate.

Liver transplantation for hepatocellular carcinoma: Where do we stand?

Hepatocellular carcinoma represents an important cause of morbidity and mortality worldwide. It is the sixth most common cancer and the fourth leading cause of cancer death. Liver transplantation is a key tool for the treatment of this disease in human therefore hepatocellular carcinoma is increasing as primary indication for grafting. Although liver transplantation represents an outstanding therapy for hepatocellular carcinoma, due to organ shortage, the careful selection and management of patients who may have a major survival benefit after grafting remains a fundamental question. In fact, only some stages of the disease seem amenable of this therapeutic option, stimulating the debate on the appropriate criteria to select candidates. In this review we focused on current criteria to select patients with hepatocellular carcinoma for liver transplantation as well as on the strategies (bridging) to avoid disease progression and exclusion from grafting during the stay on wait list. The treatments used to bring patients within acceptable criteria (down-staging), when their tumor burden exceeds the standard criteria for transplant, are also reported. Finally, we examined tumor reappearance following liver transplantation. This occurrence is estimated to be approximately 8%-20% in different studies. The possible approaches to prevent this outcome after transplant are reported with the corresponding results.

Long-term outcomes of hepatocellular carcinoma that underwent chemoembolization for bridging or downstaging

BACKGROUND Prospective study of 200 patients with hepatocellular carcinoma(HCC)that underwent liver transplant(LT)after drug-eluting beads transarterial chemoembolization(DEB-TACE)for downstaging versus bridging.Overall survival and tumor recurrence rates were calculated,eligibility for LT,time on the waiting list and radiological response were compared.After TACE,only patients within Milan Criteria(MC)were transplanted.More patients underwent LT in bridging group.Five-year post-transplant overall survival,recurrence-free survival has no difference between the groups.Complete response was observed more frequently in bridging group.Patients in DS group can achieve posttransplant survival and HCC recurrence-free probability,at five years,just like patients within MC in patients undergoing DEB-TACE.AIM To determine long-term outcomes of patients with HCC that underwent LT after DEB-TACE for downstaging vs bridging.METHODS Prospective cohort study of 200 patients included from April 2011 through June 2014.Bridging group included patients within MC.Downstaging group(out of MC)was divided in 5 subgroups(G1 to G5).Total tumor diameter was≤8 cm for G1,2,3,4(n=42)and was>8 cm for G5(n=22).Downstaging(n=64)and bridging(n=136)populations were not significantly different.Overall survival and tumor recurrence rates were calculated by the Kaplan-Meier method.Additionally,eligibility for LT,time on the waiting list until LT and radiological response were compared.RESULTS After TACE,only patients within MC were transplanted.More patients underwent LT in bridging group 65.9%(P=0.001).Downstaging population presented:higher number of nodules 2.81(P=0.001);larger total tumor diameter 8.09(P=0.001);multifocal HCC 78%(P=0.001);more post-transplantation recurrence 25%(P=0.02).Patients with maximal tumor diameter up to 7.05 cm were more likely to receive LT(P=0.005).Median time on the waiting list was significantly longer in downstaging group 10.6 mo(P=0.028).Five-year posttransplant overall survival was 73.5%in downstaging and 72.3%bridging groups(P=0.31),and recurrence-free survival was 62.1%in downstaging and 74.8%bridging groups(P=0.93).Radiological response:complete response was observed more frequently in bridging group(P=0.004).CONCLUSION Tumors initially exceeding the MC down-staged after DEB-TACE,can achieve post-transplant survival and HCC recurrence-free probability,at five years,just like patients within MC in patients undergoing DEB-TACE.

Comprehensive application of modern technologies in precise liver resection

BACKGROUND: Liver surgery has gone through the phases of wedge liver resection, regular resection of hepatic lobes, irregular and local resection, extracorporeal hepatectomy, hemi-extracorporeal hepatectomy and Da Vinci surgical system-assisted hepatectomy. Taking advantage of modern technologies, liver surgery is stepping into an age of precise liver resection. This review aimed to analyze the comprehensive application of modern technologies in precise liver resection. DATA SOURCE: PubMed search was carried out for English-language articles relevant to precise liver resection, liver anatomy, hepatic blood inflow blockage, parenchyma transection, and down-staging treatment. RESULTS: The 3D image system can imitate the liver operation procedures, conduct risk assessment, help to identify the operation feasibility and confirm the operation scheme. In addition, some techniques including puncture and injection of methylene blue into the target Glisson sheath help to precisely determine the resection. Alternative methods such as Pringle maneuver are helpful for hepatic blood inflow blockage in precise liver resection. Moreover, the use of exquisite equipment for liver parenchyma transection, such as cavitron ultrasonic surgical aspirator, ultrasonic scalpel, Ligasure and Tissue Link is also helpful to reduce hemorrhage in liver resection, or even operate exsanguinous liver resection without blocking hepatic blood flow. Furthermore, various down-staging therapies including transcatheter arterial chemoembolization and radio-frequency ablation were appropriate for unresectable cancer, which reverse the advanced tumor back to early phase by local or systemic treatment so that hepatectomy or liver transplantation is possible.CONCLUSIONS: Modern technologies mentioned in this paper are the key tool for achieving precise liver resection and can effectively lead to maximum preservation of anatomical structural integrity and functions of the remnant liver. In addition, large randomized trials are needed to evaluate the usefulness of these technologies in patients with hepatocellular carcinoma who have undergone precise liver resection.

Neoadjuvant treatment strategies for intrahepatic cholangiocarcinoma

Intrahepatic cholangiocarcinoma(ICC)is the second most common primary liver malignancy and is increasing in incidence.Long-term outcomes are optimized when patients undergo margin-negative resection followed by adjuvant chemotherapy.Unfortunately,a significant proportion of patients present with locally advanced,unresectable disease.Furthermore,recurrence rates are high even among patients who undergo surgical resection.The delivery of systemic and/or liver-directed therapies prior to surgery may increase the proportion of patients who are eligible for surgery and reduce recurrence rates by prioritizing early systemic therapy for this aggressive cancer.Nevertheless,the available evidence for neoadjuvant therapy in ICC is currently limited yet recent advances in liver directed therapies,chemotherapy regimens,and targeted therapies have generated increasing interest its role.In this article,we review the rationale for,current evidence for,and ongoing research efforts in the use of neoadjuvant therapy for ICC.

Delaying surgery after neoadjuvant chemoradiotherapy improves prognosis of rectal cancer

AIM To investigate the prognostic effect of a delayed interval between neoadjuvant chemoradiotherapy(CRT) and surgery in locally advanced rectal cancer.METHODS We evaluated 87 patients with locally advanced mid-or distal rectal cancer undergoing total mesorectal excision following an interval period after neoadjuvant CRT at ?i?li Hamidiye Etfal Training and Research Hospital,Istanbul between January 2009 and January 2014.Patients were divided into two groups according to the intervalbefore surgery: < 8 wk(group Ⅰ) and ≥ 8 wk(group Ⅱ).Data related to patients,cancer characteristics and pathological examination were collected and analyzed.RESULTS When the distribution of timing between group Ⅰ(n = 45) and group Ⅱ(n = 42) was viewed,comparison of interval periods(median ± SD) of groups showed a significant difference of as 5 ± 1.28 wk in group Ⅰ and 10.1 ± 2.2 wk in group Ⅱ(P < 0.001).The median follow-up period for all patients was 34.5(9.9-81) mo.group Ⅱ had significantly higher rates of pathological complete response(p CR) than group Ⅰ had(19% vs 8.9%,P = 0.002).Rate of tumor regression grade(TRG) poor response was 44.4% in group Ⅰ and 9.5% in group Ⅱ(P < 0.002).A poor pathological response was associated with worse disease-free survival(P = 0.009).The interval time did not show any association with local recurrence(P = 0.79).CONCLUSION Delaying the neoadjuvant CRT-surgery interval may provide nodal down-staging,improve p CR rate,and decrease the rate of TRG poor response.

Liver transplantation for intermediate hepatocellular carcinoma: An adaptive approach

Hepatocellular carcinoma is becoming an increasing indication for liver transplantation, but selection and allocation of patients are challenging because of organ shortages. Conventional Milan criteria are the reference for the selection of patients worldwide, but many expanded criteria, like University of California San Francisco criteria and up-to-7 criteria, have demonstrated that survival and recurrence results are lower than those for restricted indications. Correct staging is crucial and should include surrogate markers of biological aggressiveness(α-fetoprotein, response to loco-regional treatments). Successful down-staging can select between patients with tumor burden initially beyond transplantation criteria those with a more favorable biology, provided a 3-mo stability in meeting the transplantation criteria. Allocation rules are constantly adjusted to minimize the imbalance between the priorities of candidates with and without hepatocellular carcinoma, and take into account local donor rate and waitlist dynamics. Recently, Mazzaferro et al proposed a benefit-oriented "adaptive approach", in which the selection and allocation of patients are based on their response to non-transplantation treatments: low priority for transplantation in case of complete response, high priority in case of partial response or recurrence, and no listing in case of progression beyond transplantation criteria.