Liver resection and transplantation for intrahepatic cholangiocarcinoma

The incidence of intrahepatic cholangiocarcinoma (iCCA) is increasing worldwide. Although several advances have been made in the past decades to better understand this complex malignancy and to develop new treatment strategies, the prognosis of iCCA remains dismal. Liver resection (LR) is the mainstay of treatment but only a minority of patients are amenable to surgery. In most cases, patients with iCCA will require a major hepatectomy for complete resection of the tumour. This may be contraindicated or increase the surgical burden in patients with chronic liver disease and small remnant liver volume. Lymphadenectomy with a minimal harvest of 6 lymph nodes is considered adequate, as microscopic nodal metastases have been shown in more than 40% of patients. Current 5-year overall survival following LR is in the range of 25%\u201340%. For locally advanced disease not amenable to upfront LR, neoadjuvant locoregional therapies may be used with the aim of converting these patients to resectability or even to transplantation in well-selected cases. Recent studies have shown that liver transplantation (LT) might be a treatment option for patients with unresectable very-early iCCA (i.e. 642 cm), with survival outcomes comparable to those of hepatocellular carcinoma. In patients with unresectable, advanced tumours, confined to the liver who achieve sustained response to neoadjuvant treatment, LT may be considered an option within prospective protocols. The role of adjuvant therapies in iCCA is still under debate. Herein, we review the recent advances in the surgical treatment of iCCA and examine its correlation with locoregional therapies, adjuvant and neo-adjuvant strategies

Resection or transplant‐listing for solitary hepatitis C‐associated hepatocellular carcinoma: an intention‐to‐treat analysis

AbstractObjectivesThe relative roles of liver resection (LR) and liver transplantation (LT) in the treatment of a solitary hepatocellular carcinoma (HCC) remain unclear. This study was conducted to provide a retrospective intention‐to‐treat comparison of these two curative therapies.MethodsRecords maintained at the study centre for all patients treated with LR or listed for LT for hepatitis C‐associated HCC between January 2002 and December 2007 were reviewed. Inclusion criteria required: (i) an initial diagnosis of a solitary HCC lesion measuring ≤ 5 cm, and (ii) Child–Pugh class A or B cirrhosis. The primary endpoint analysed was intention‐to‐treat survival.ResultsA total of 75 patients were listed for transplant (LT‐listed group) and 56 were resected (LR group). Of the 75 LT‐listed patients, 23 (30.7%) were never transplanted because they were either removed from the waiting list (n = 13) or died (n = 10). Intention‐to‐treat median survival was superior in the LR group compared with the LT‐listed group (61.8 months vs. 30.6 months), but the difference did not reach significance. Five‐year recurrence was higher in the LR group than in the 52 LT patients (71.5% vs. 30.5%; P < 0.001).ConclusionsIn the context of limited donor organ availability, partial hepatectomy represents an efficacious primary approach in properly selected patients with hepatitis C‐associated HCC

The high-risk recipient: the Eighth Annual American Society of Transplant Surgeons’ State-of-the-Art Winter Symposium

Sung RS, Pomfret EA, Andreoni KA, Baker TB, Peters TG. The high-risk recipient: the Eighth Annual American Society of Transplant Surgeons’ State-of-the-Art Winter Symposium. Clin Transplant 2010: 24: 23–28. © 2009 John Wiley & Sons A/S.The evolution of organ transplantation has produced results so successful that many transplant programs commonly see recipients with medical risks, which in the past, would have prohibited transplantation. The Eighth Annual American Society of Transplant Surgeons State-of-the-Art Winter Symposium focused on the high-risk recipient. The assessment of risk has evolved over time, as transplantation has matured. The acceptance of risk associated with a given candidate today is often made in consideration of the relative value of the organ to other candidates, the regulatory environment, and philosophical notions of utility, equity, and fairness. In addition, transplant programs must balance outcomes, transplant volume, and the costs of organ transplantation, which are impacted by high-risk recipients. Discussion focused on various types of high-risk recipients, such as those with coronary artery disease, morbid obesity, and hepatitis C; strategies to reduce risk, such as down-staging of hepatocellular carcinoma and treatment of pulmonary hypertension; the development of alternatives to transplantation; and the degree to which risk can or should be used to define candidate selection. These approaches can modify the impact of recipient risk on transplant outcomes and permit transplantation to be applied successfully to a greater variety of patients.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/78695/1/j.1399-0012.2009.01156.x.pd

Functional abdominal complaints occurred frequently in living liver donors after donation

Background. Donor outcome after living donor liver transplantation has not been examined extensively with regard to postoperative abdominal complaints. We wanted to examine the extent and type of abdominal complaints after removal of a part of the liver and gallbladder in living donors as well as potential similarities with known disorders. Methods. Twelve patients of mixed ethnicity, nine men, aged 18-45 years, and three women, aged 32-46 years, were enrolled in the study during a 3-year period and followed up at 6 and 12 months. Patients filled out questionnaires pertaining to functional abdominal complaints (FAC) using a recognized questionnaire, Rome II, as well as specific abdominal pain symptoms known from gallstone disease. Results. FAC occurred in 11 patients at 6 months and nine patients at 12 months while abdominal pain occurred in seven and six patients, respectively. Three patients had FAC but no abdominal pain while two patients had no complaints at 12 months. Irritable bowel syndrome (IBS) was found in the majority of patients. Conclusions. FAC and pain seemed to indicate a general postoperative disorder, of a psychosomatic character, and not connected with removal of part of the liver and gallbladder in particular. However, the occurrence of IBS and FD should merit attention, as they are known to impair quality of life.Fil: Søndenaa, Karl. University of Bergen; NoruegaFil: Gondolesi, Gabriel Eduardo. Fundación Favaloro; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Roayaie, Sasan. No especifíca;Fil: Goldman, Jody S.. No especifíca;Fil: Hausken, Trygve. University of Bergen; NoruegaFil: Schwartz, Myron E.. No especifíca

Prognostic Significance of Lymph Node Metastases in Small Intestinal Neuroendocrine Tumors

Background/Aims: Current staging guidelines for small intestinal neuroendocrine tumors (SI-NETs) differentiate between the presence (N1) and absence (N0) of lymph node (LN) metastases. However, the prognostic significance of the extent of LN involvement remains unknown. In this study, we used data from a population-based cancer registry to examine whether involvement of a higher number of LNs is associated with worse survival. Methods: We used the Surveillance, Epidemiology, and End Results (SEER) database to identify patients with histologically confirmed, surgically resected SI-NETS diagnosed between 1988 and 2010. Patients were classified into three groups by the LN ratio (number of positive LNs/number of total LNs examined, LNR):0.2-0.5, and \u3e0.5. We used the Kaplan-Meier method and Cox models to assess NET cancer-specific survival differences (up to 10 years from diagnosis) according to LNR status. Results: We identified 2,984 surgically resected patients with stage IIIb (N1, M0) SI-NETs with detailed LN data. More than half of the NETs were located in the ileum. A higher LNR was significantly associated with worse NET cancer-specific survival (p \u3c 0.0001). Ten-year NET-specific survival was 85, 77, and 74% for patients in the0.2-0.5, and \u3e0.5 LNR groups, respectively. In stratified analyses, higher LNR groups had worse survival only in early tumor (T1, T2) disease (p \u3c 0.0001). Conclusions: The extent of LN involvement provides independent prognostic information on patients with LN-positive SI-NETs. This information may be used to identify patients at high risk of recurrence and inform decisions about the use of adjuvant therapy. (C) 2015 S. Karger AG, Base

Differential Protein Expression in Small Intestinal Neuroendocrine Tumors and Liver Metastases

OBJECTIVE: Small intestinal neuroendocrine tumors (SI-NETs) are often detected after they have become metastatic. Using a novel protein array, we identified pathways important in SI-NET metastasis development in surgically resected patients. METHODS: Paired primary tumors and liver metastases from 25 patients undergoing surgical resection for metastatic SI-NETs were harvested. Extracted proteins were separated by sodium dodecyl sulfate gel and multiplex immunoblots were performed with 136 antibodies. Significant Analysis of Microarray was used to select for differentially expressed proteins. A tissue microarray was constructed from 27 archived specimens and stained by immunohistochemistry. RESULTS: Comparing primary SI-NETs with matched normal small-bowel mucosa, 9 proteins were upregulated and cyclin E was downregulated. The SI-NET liver metastases demonstrated upregulation of P-ERK and p27 but downregulation of CDK2 and CDC25B. When comparing primary SI-NET with their paired liver metastases, cyclin E demonstrated a significant upregulation in the liver metastasis. Tissue microarray demonstrated higher p38 expression and lower Cdc 25b expression in SI-NETs versus liver metastases and confirmed higher expression of p27 in liver metastases versus normal liver. CONCLUSIONS: Few studies have compared protein expression in paired primary and metastatic SI-NETs. Our findings reveal changes in a limited number of proteins, suggesting that these may be targets for therapy

Downstaging of Hepatocellular Carcinoma Prior to Liver Transplant: Is There a Role for Adjuvant Sorafenib in Locoregional Therapy?

Hepatocellular carcinoma (HCC) remains a common cause of mortality worldwide. Liver transplantation has emerged as the optimal treatment for cirrhotic patients with HCC; however, the shortage of donor organs leaves waitlisted patients at risk for disease progression beyond transplant criteria. Prevention of waitlist dropout has fueled investigation into a wide array of locoregional therapies for the management of HCC in candidates awaiting liver transplantation. We present a patient with HCC who underwent treatment with sorafenib, which resulted in a remarkable reduction in tumor burden to allow for liver transplant listing

Tumor Response to Transcatheter Arterial Chemoembolization in Recurrent Hepatocellular Carcinoma after Living Donor Liver Transplantation

Objective To evaluate the tumor response and patient survival rate following transcatheter arterial chemoembolization (TACE) in recurrent hepatocellular carcinoma (r-HCC) after living donor liver transplantation (LDLT). Materials and Methods Twenty-eight patients with r-HCC underwent one or more cycles of TACE after LDLT (mean, 2.5 cycles). After a mixture of iodized oil and anti-cancer drugs was injected via the arteries feeding the tumors, these vessels were embolized with a gelatin sponge. Tumor response was determined by follow-up CT imaging on all patients four weeks after each TACE procedure. Patient survival was calculated using the Kaplan-Meier survival curve. Results After TACE, targeted tumor reduced in size by 25% or more in 19 of the 28 study patients (67.9%). However, intrahepatic recurrence or extrahepatic metastasis occurred in 21 of the 28 patients (75.0%) during the 3-month follow-up period and in 26 of the 28 patients (92.9%) during the 6-month period following TACE. Extrahepatic metastasis was noted in 18 of the 28 patients (64.3%). The 1-, 3- and 5-year survival rates following TACE were 47.9, 6.0 and 0%, respectively, with a mean survival of nine months in all patients. There were no significant complications related to TACE. Conclusion TACE produces an effective tumor response for targeted r-HCC after LDLT. However, the survival rate of patients with r-HCC after LDLT is poor due to extrahepatic metastasis and intrahepatic recurrence.ope

Development of pre and post-operative models to predict early recurrence of hepatocellular carcinoma after surgical resection

Background & Aims Resection is the most widely used potentially curative treatment for patients with early hepatocellular carcinoma (HCC). However, recurrence within 2 years occurs in 30–50% of patients, being the major cause of mortality. Herein, we describe 2 models, both based on widely available clinical data, which permit risk of early recurrence to be assessed before and after resection. Methods A total of 3,903 patients undergoing surgical resection with curative intent were recruited from 6 different centres. We built 2 models for early recurrence, 1 using preoperative and 1 using pre and post-operative data, which were internally validated in the Hong Kong cohort. The models were then externally validated in European, Chinese and US cohorts. We developed 2 online calculators to permit easy clinical application. Results Multivariable analysis identified male gender, large tumour size, multinodular tumour, high albumin-bilirubin (ALBI) grade and high serum alpha-fetoprotein as the key parameters related to early recurrence. Using these variables, a preoperative model (ERASL-pre) gave 3 risk strata for recurrence-free survival (RFS) in the entire cohort – low risk: 2-year RFS 64.8%, intermediate risk: 2-year RFS 42.5% and high risk: 2-year RFS 20.7%. Median survival in each stratum was similar between centres and the discrimination between the 3 strata was enhanced in the post-operative model (ERASL-post) which included 'microvascular invasion'. Conclusions Statistical models that can predict the risk of early HCC recurrence after resection have been developed, extensively validated and shown to be applicable in the international setting. Such models will be valuable in guiding surveillance follow-up and in the design of post-resection adjuvant therapy trials. Lay summary The most effective treatment of hepatocellular carcinoma is surgical removal of the tumour but there is often recurrence. In this large international study, we develop a statistical method that allows clinicians to estimate the risk of recurrence in an individual patient. This facility enhances communication with the patient about the likely success of the treatment and will help in designing clinical trials that aim to find drugs that decrease the risk of recurrence