Comparison of the prognostic accuracy of the sixth and seventh editions of the TNM classification for intrahepatic cholangiocarcinoma

Background

The seventh TNM edition introduced a new, specific staging structure for intrahepatic cholangiocarcinoma (IHC).

Objective

To compare the accuracy of the sixth and the new seventh edition to predict survival after hepatectomy for IHC.

Methods

In all, 434 consecutive patients who underwent hepatectomy at 16 tertiary-care centres (1990–2008) were identified. End points were overall (OS) and recurrence-free survival (RFS) for both T cohorts and stage strata.

Results

After a median follow-up of 32.4 months, 3- and 5-year OS and RFS estimates were 47.1% and 32.9%, and 26.5% and 19.1%, respectively. Overall, both the editions were statistically significant discriminators of OS and RFS (P < 0.05). However, the survival curves of the new T2a and T2b cohorts appear superimposed. Conversely, the old T2 and T3 cohorts accurately stratify patients into distinct prognostic groups (P < 0.01). The seventh edition does not show monotonicity of gradients (the T4 category demonstrates significantly better OS and RFS compared with T2 patients). The seventh edition stage I and II are significantly different whereas the old stage I and II were not.

Conclusions

The new seventh edition of the AJCC/UICC Staging System proved to be adequate although further studies are need to confirm its superiority compared with the previous edition.     

Role of hepatic intra-arterial therapies in metastatic neuroendocrine tumours (NET): guidelines from the NET-Liver-Metastases Consensus Conference

Objectives

Liver metastasis from a neuroendocrine tumour (NET) represents a significant clinical entity. A multidisciplinary group of experts was convened to develop state-of-the-art recommendations for its management.

Methods

Peer-reviewed published reports on intra-arterial therapies for NET hepatic metastases were reviewed and the findings presented to a jury of peers. The therapies reviewed included transarterial embolization (TAE), transarterial chemoembolization (TACE) and radioembolization (RE). Two systems were used to evaluate the level of evidence in each publication: (i) the US National Cancer Institute (NCI) system, and (ii) the GRADE system.

Results

Eighteen publications were reviewed. These comprised 11 reports on TAE or TACE and seven on RE. Four questions posed to the panel were answered and recommendations offered.

Conclusions

Studies of moderate quality support the use of TAE, TACE and RE in hepatic metastases of NETs. The quality and strength of the reports available do not allow any modality to be determined as superior in terms of imaging response, symptomatic response or impact on survival. Radioembolization may have advantages over TAE and TACE because it causes fewer side-effects and requires fewer treatments. Based on current European Neuroendocrine Tumor Society (ENETS) Consensus Guidelines, RE can be substituted for TAE or TACE in patients with either liver-only disease or those with limited extrahepatic metastases.     

Liver transplantation for neuroendocrine tumour liver metastases

Objective

Search and review of available literature were made to define the indications for and timing of liver transplantation for neuroendocrine tumour (NET) liver metastases.

Methods

Electronic bibliographical databases were searched. Prospective and retrospective cohort studies and case–controlled studies were used for qualitative and quantitative synthesis of the systematic review. Reports of patients with liver transplantation alone for NET liver metastases of any origin or combined with resection of extrahepatic tumour deposits were recruited.

Results

The number of patients who have undergone liver transplantation for NET liver metastases is 706. The post-transplant 5-year survival rate from the time of diagnosis was approximately 70%. NET patients with metastases confined to the liver and not poorly differentiated are favourable candidates for liver transplantation. Selection of patients based on evolution of tumours over 6 months is not recommended.

Conclusion

Non-resectable NET liver metastasis resistant to medical treatment and confined to the liver is an accepted indication for liver transplantation.     

Long-term survival in laparoscopic vs open resection for colorectal liver metastases: inverse probability of treatment weighting using propensity scores

Background

This study compares long-term outcomes between intention-to-treat laparoscopic and open approaches to colorectal liver metastases (CLM), using inverse probability of treatment weighting (IPTW) based on propensity scores to control for selection bias.

Method

Patients undergoing liver resection for CLM by 5 surgeons at 3 institutions from 2000 to early 2014 were analysed. IPTW based on propensity scores were generated and used to assess the marginal treatment effect of the laparoscopic approach via a weighted Cox proportional hazards model.

Results

A total of 298 operations were performed in 256 patients. 7 patients with planned two-stage resections were excluded leaving 284 operations in 249 patients for analysis. After IPTW, the population was well balanced. With a median follow up of 36 months, 5-year overall survival (OS) and recurrence-free survival (RFS) for the cohort were 59% and 38%. 146 laparoscopic procedures were performed in 140 patients, with weighted 5-year OS and RFS of 54% and 36% respectively. In the open group, 138 procedures were performed in 122 patients, with a weighted 5-year OS and RFS of 63% and 38% respectively. There was no significant difference between the two groups in terms of OS or RFS.

Conclusion

In the Brisbane experience, after accounting for bias in treatment assignment, long term survival after LLR for CLM is equivalent to outcomes in open surgery.     

A meta-analysis of adjuvant therapy after potentially curative treatment for hepatocellular carcinoma

BACKGROUND:

The high recurrence rate of hepatocellular carcinoma (HCC) after potentially curative treatment determines the long-term prognosis.

OBJECTIVE:

To evaluate the efficacy and safety of adjuvant therapies in patients with HCC who have undergone hepatic resection, transplantation or locoregional ablation therapy.

METHODS:

Several databases were searched to identify randomized controlled trials (RCTs) fulfilling the predefined selection criteria. Meta-analyses were performed to estimate the effects of adjuvant therapies of any modality on recurrence-free survival (RFS) and overall survival (OS).

RESULTS:

Eight adjuvant modalities were identified from 27 eligible RCTs conducted predominantly in Asian populations comparing adjuvant with no adjuvant therapy. Adjuvant chemotherapy, internal radiation and heparanase inhibitor PI-88 therapy failed to improve RFS or OS, while interferon (IFN) therapy yielded significant survival results. The findings of adjuvant vitamin analogue therapy required further examination. Adjuvant adoptive immunotherapy conferred significant benefit for RFS but not for OS. Although cancer vaccine therapy and radioimmunotherapy may improve survival after radical surgery, the results were from single, small-scale trials. Severe side effects were observed in the studies of adjuvant chemotherapy and of IFN therapy.

CONCLUSIONS:

Adjuvant IFN therapy can improve both RFS and OS; however, the benefits of using this agent should be weighed against its side effects. Combination of systemic and transhepatic arterial chemotherapy is not recommended for HCC after potentially curative treatment. Other adjuvant therapies produce limited success for survival. Additional RCTs with proper design are required to establish the role of adjuvant therapies for HCC.     

Factors affecting prognosis of small hepatocellular carcinoma in Taiwanese patients following hepatic resection

BACKGROUND:

Small hepatocellular carcinoma (HCC) affects millions of individuals worldwide. Surveillance of high-risk patients increases the early detection of small HCC.

OBJECTIVE:

To identify prognostic factors affecting the overall survival (OS) and recurrence-free survival (RFS) of patients with small HCC.

METHODS:

The present prospective study enrolled 140 Taiwanese patients with stage I or stage II small HCC. Clinical parameters of interest included operation type, tumour size, tumour histology, Child-Pugh class, presence of hepatitis B surface antigen and liver cirrhosis, hepatitis C status, alpha-fetoprotein, total bilirubin and serum albumin levels, and administration of antiviral and salvage therapies.

RESULTS:

Tumour size correlated significantly with poorer OS in patients with stage I small HCC (P=0.014); however, patients with stage II small HCC experienced a significantly poorer RFS (P=0.033). OS rates did not differ significantly between patients with stage I and stage II small HCC. Tumour margins, tumour histology and cirrhosis did not significantly affect OS or RFS (P>0.05).

DISCUSSION:

Increasing tumour size has generally been associated with poorer prognoses in cases of HCC. The present study verified the relationship between small HCC tumour size and OS; however, a reduction in OS with increasing tumour size was demonstrated for patients with stage I – but not for stage II – small HCC.

CONCLUSION:

Patients with stage II small HCC may benefit from aggressive surveillance for tumour recurrence and appropriate salvage treatment. Further studies are needed for additional stratification of stage I patients to identify those at increased risk of death.     

Prognostic significance of lymph node ratio after resection of peri-hilar cholangiocarcinoma

Background

Lymph node (LN) metastases are a major negative prognostic factor for peri-hilar cholangiocarcinoma (PCC). Prognostic significance of the extent of LN dissection, number of metastatic LN and the lymph node ratio (LNR) are still under debate.

Aims

The aims of the present study were to evaluate the prognostic value of the LN status, the total number of LNs evaluated and LNR in PCC.

Methods

Between 1990 and 2008, 62 patients with PCC submitted to surgical resection with curative intent were retrospectively evaluated. Number and status of harvested LN were recorded.

Results

In 53 patients (85.4%) regional lymphadenectomy was performed. Median number of LNs examined was 7 (range 1–25). Median survival was 41.9 months in patients with N0 compared with 22.7 months in 21 patients (39.6%) with N+ (P = 0.03). Median survival was 3, 18.5 and 29 months for patients with 0, 1–3 and >3 LN retrieved, respectively (P < 0.01). Five-year survival for patients above and below the LNR cut-off value of 0.25 was 0% and 22.5%, respectively (P = 0.03).

Conclusions

LN metastases are a major prognostic factor for survival after surgical resection of PCC. The number of LN harvested and LNR showed high prognostic value.     

Intraductal papillary mucinous neoplasm (IPMN) with high-grade dysplasia is a risk factor for the subsequent development of pancreatic ductal adenocarcinoma

Background

Non-invasive intraductal papillary mucinous neoplasm (IPMN) with high-grade dysplasia and IPMN-associated invasive pancreatic ductal adenocarcinoma (PDAC) are frequently included under the term “malignancy”. The goal of this study is to clarify the difference between these two entities.

Methods

From 1996 to 2013, data of 616 patients who underwent pancreatic resection for an IPMN were reviewed.

Results

The median overall survival for patients with IPMN with high-grade dysplasia (92 months) was similar to survival for patients with IPMN with low/intermediate-grade dysplasia (118 months, p = 0.081), and superior to that of patients with IPMN-associated PDAC (29 months, p < 0.001). IPMN-associated PDAC had lymph node metastasis in 53%, perineural invasion in 58%, and vascular invasion in 33%. In contrast, no lymph node metastasis, perineural or vascular invasion was observed with high-grade dysplasia. None of the patients with IPMN with high-grade dysplasia developed recurrence outside the remnant pancreas. In stark contrast 58% of patients with IPMN-associated PDAC recurred outside the remnant pancreas. The rate of progression within the remnant pancreas was significant in patients with IPMN with high-grade (24%) and with low/intermediate dysplasia (22%, p = 0.816).

Conclusion

Non-invasive IPMN with high-grade dysplasia should not be considered a malignant entity. Compared to patients with IPMN with low/intermediate-grade dysplasia, those with high-grade dysplasia have an increased risk of subsequent development of PDAC in the remnant pancreas.     

Dynamic Changes of Treg and Th17 Cells and Related Cytokines Closely Correlate With the Virological and Biochemical Response in Chronic Hepatitis B Patients Undergoing Nucleos(t)ide Analogues Treatment

Background:

The restoration of HBV-specific T-cell response during antiviral therapy is associated with CD4+T-cell activity. Treg cells and Th17 cells are subtypes of CD4+T cell. However, it has remained unknown how the Treg and Th17 cells and their associated cytokines affect nucleos(t)ide analogues (NA) antiviral efficacy.

Objectives:

The aim of the present study was to provide a new insight to evaluate the NA antiviral therapy for patients with chronic hepatitis B (CHB).

Patients and Methods:

Forty-four CHB patients hospitalized between July 2010 and August 2011 were enrolled in this study. They were received NA (entecavir, lamivudine and adefovir) treatment for 14.42 ± 13.08 weeks, and the peripheral blood was collected. The frequencies of Treg and Th17 cells were detected by flow cytometric analysis, and the levels of IL-10, TGF-β1, IL-17 and IL-23 were measured by enzyme-linked immunosorbent assay (ELISA).

Results:

In complete and partial-responders, Treg cells frequencies and IL-10, TGF-β1, IL-23 levels were all decreased significantly after NA therapy, while Th17 cells and the IL-17 levels were increased slightly. Treg/Th17 ratio was only dramatically declined in complete-responders. But there was no significant difference in non-responders. Either HBV DNA decreased by at least 2 log copies /mL or ALT turned to normal level, Treg cells frequencies and IL-10, TGF-β1, IL-23 levels were significantly reduced. Meanwhile, Treg cells were positively correlated with HBV DNA and ALT.

Conclusions:

The changes of Treg and Th17 cells and their associated cytokines were related to virological and biochemical responses.     

Factors linked to longterm survival of patients with hepatocellular carcinoma accompanied by tumour thrombus in the major portal vein after surgical resection

Objectives

The prognosis in patients with hepatocellular carcinoma (HCC) accompanied by main portal vein tumour thrombus (MPVTT) is poor. The aim of this study was to clarify the factors linked to survival of >5 years after hepatectomy in HCC patients with MPVTT.

Methods

Twenty-nine HCC patients with MPVTT were divided into two groups comprising, respectively, patients who survived >5 years after hepatectomy (survivors, n = 5) and those who did not (non-survivors, n = 24). The two groups were compared.

Results

Overall survival rates at 1, 3 and 5 years were 62.1%, 24.1% and 17.2%, respectively. Four (80.0%) 5-year survivors had recurrences of HCC in which the number of recurrent nodules was under four. Three (21.4%) of the 14 non-survivors who underwent curative resection experienced recurrences of HCC and all of them demonstrated fewer than four recurrent nodules (P = 0.0114). Local therapy, such as radiofrequency ablation and resection of recurrence, had more often been used in survivors than in non-survivors (P = 0.0364).

Conclusions

Although surgical outcomes in patients with HCC accompanied by MPVTT are unsatisfactory, some patients do enjoy longterm survival. When the number of recurrent nodules is less than four, local therapy should be selected with the aim of achieving 5-year survival.     

A 21‐year analysis of stage I gallbladder carcinoma: is cholecystectomy alone adequate?

Objectives

Gallbladder carcinoma (GBC) is a rare disease that is often diagnosed incidentally in its early stages. Simple cholecystectomy is considered the standard treatment for stage I GBC. This study was conducted in a large cohort of patients with stage I GBC to test the hypothesis that the extent of surgery affects survival.

Methods

The National Cancer Institute''s Surveillance, Epidemiology and End Results (SEER) database was queried to identify patients in whom microscopically confirmed, localized (stage I) GBC was diagnosed between 1988 and 2008. Surgical treatment was categorized as cholecystectomy alone, cholecystectomy with lymph node dissection (C + LN) or radical cholecystectomy (RC). Age, gender, race, ethnicity, T1 sub-stage [T1a, T1b, T1NOS (T1 not otherwise specified)], radiation treatment, extent of surgery, cause of death and survival were assessed by log-rank and Cox''s regression analyses.

Results

Of 2788 patients with localized GBC, 1115 (40.0%) had pathologically confirmed T1a, T1b or T1NOS cancer. At a median follow-up of 22 months, 288 (25.8%) had died of GBC. Five-year survival rates associated with cholecystectomy, C + LN and RC were 50%, 70% and 79%, respectively (P < 0.001). Multivariate analysis showed that surgical treatment and younger age were predictive of improved disease-specific survival (P < 0.001), whereas radiation therapy portended worse survival (P = 0.013).

Conclusions

In the largest series of patients with stage I GBC to be reported, survival was significantly impacted by the extent of surgery (LN dissection and RC). Cholecystectomy alone is inadequate in stage I GBC and its use as standard treatment should be reconsidered.     

Role of radical surgery in patients with stage IV gallbladder cancer

Objectives

The role of surgery in stage IV gallbladder (GB) cancer is not well established. This study analyses prognostic factors in patients with stage IV GB cancer following surgical resection with the aim of identifying a subgroup of patients who might benefit from surgical resection.

Methods

Clinicopathological details were analysed for 94 patients who were surgically treated for stage IV GB cancer at Seoul National University Hospital.

Results

Median survival was 8 months in patients with either stage IVa or IVb disease. Sixteen patients (17.0%) underwent resection with curative intent, which increased overall survival over that in patients undergoing palliative surgery (P < 0.001). No survival benefit was seen following surgery with curative intent in patients with stage IVa disease (P = 0.764). Surgery with curative intent resulted in a survival benefit in patients with stage IVb disease, patients with an isolated liver metastasis near the GB bed (median survival: 31 months vs. 9 months; P < 0.001) and patients with limited numbers of peritoneal implantations (median survival: 20 months vs. 6 months; P = 0.002). Preoperative serum carcinoembryonic antigen (CEA) (P = 0.018), surgery with curative intent (P = 0.045) and adjuvant chemotherapy (P = 0.002) were independent prognostic factors in patients with stage IV GB cancer.

Conclusions

Surgery in combination with systemic chemotherapy may be beneficial in carefully selected patients with stage IVb GB cancer.     

Monitoring of CD4+CD25highIL-7Rαhigh activated T Cells in Kidney Transplant Recipients

Summary

Background and objectives

In humans, circulating CD4⁺CD25^high T cells contain mainly regulatory T cells (Treg; FoxP3⁺IL-7Rα^low), but a small subset is represented by activated effector T cells (Tact; FoxP3⁻IL-7Rα^high). The balance between Tact and Treg may be important after transplantation. The aim of this study was first to analyze and correlate CD4⁺CD25^high Tact and Treg with the clinical status of kidney transplant recipients and second to study prospectively the effect of two immunosuppressive regimens on Tact/Treg during the first year after transplantation.

Design, setting, participants, & measurements

CD4⁺CD25^high Tact and Treg were analyzed by flow cytometry, either retrospectively in 90 patients greater than 1 year after kidney transplantation (cross-sectional analysis) or prospectively in 35 patients receiving two immunosuppressive regimens after kidney transplantation (prospective analysis).

Results

A higher proportion of Tact and a lower proportion of Treg were found in the majority of kidney recipients. In chronic humoral rejection, a strikingly higher proportion of Tact was present. A subgroup of stable recipients receiving calcineurin inhibitor–free immunosuppression (mycophenolate mofetil, azathioprine, or sirolimus) had Tact values that were similar to healthy individuals. In the prospective analysis, the proportion of Tact significantly increased in both immunosuppression groups during the first year after transplantation.

Conclusions

These data highlight distinct patterns in the proportion of circulating Tact depending on the clinical status of kidney recipients. Moreover, the prospective analysis demonstrated an increase in the proportion of Tact, regardless of the immunosuppressive regimen. The measurement of Tact, in addition to Treg, may become a useful immune monitoring tool after kidney transplantation.     

Predictors of response to radio-embolization (TheraSphere®) treatment of neuroendocrine liver metastasis

Background

Neuroendocrine tumours (NET) frequently metastasize to the liver. NET liver metastasis has been shown to respond to Yttrium-90 microspheres therapy. The aims of the present study were to define factors that predict the response to radio-embolization in patients with NET liver metastases.

Methods

From January 2006 until March 2009, all patients with NET liver metastasis that received radio-embolization using TheraSphere® (glass microspheres) were reviewed. The response was determined by a change in the percentage of necrosis (ΔN%) after the first radio-embolization based on the modified RECIST criteria (mRECIST) criteria. The following confounding variables were measured: age, gender, size of the lesions, liver involvement, World Health Organization (WHO) classification, the presence of extra-hepatic metastasis, octereotide treatment and previous operative [surgery and (RFA)] and non-operative treatments (chemo-embolization and bland-embolization).

Results

In all, 25 patients were identified, with a median follow-up of 21.7 months. The median age was 64.6 years, 28% had extra-hepatic metastasis and 56% were WHO stage 2. Post-treatment, the mean ΔN% was 48.4%. Previous surgical therapy was a significant predictor of the response with a response rate of 66.7 ΔN% vs. 31.5 ΔN% (P = 0.02). Bilateral liver disease, a high percentage of liver involvement and large metastatic lesions were inversely related to the degree of tumour response although did not reach statistical significance.

Conclusion

Radio-embolization increased the necrosis of NET liver metastasis mainly in patients with less bulky disease. This may imply that surgical therapy before radio-embolization would increase the response rates.     

Surgical resection for hilar cholangiocarcinoma: experience improves resectability

Objectives

In hilar cholangiocarcinoma, resection provides the only opportunity for longterm survival. A US experience of hilar cholangiocarcinoma was examined to determine the effect of clinical experience on negative margin (R0) resection rates.

Methods

We conducted a retrospective analysis of 110 consecutive hilar cholangiocarcinoma patients presenting over an 18-year period. Analyses were performed using chi-squared, Wilcoxon rank sum and Kaplan–Meier methods, and multivariable Cox and logistic regression modelling.

Results

Of the 110 patients in the cohort, 59.1% were male and 90.9% were White. The median patient age was 64 years. A total of 59 (53.6%) patients underwent resection; 37 of these demonstrated R0. The 30-day mortality rate was 5.1%; the complication rate was 39.0%. The rate of resectability increased over time (36.4% vs. 70.9%; P = 0.001), as did the percentage of R0 resections (10.9% vs. 56.5%; P < 0.001). Of the 59 patients who underwent resection, 23 (39.0%) experienced recurrence. Multivariable Cox regression analysis identified resection margins [hazard ratio (HR) = 4.124 for positive vs. negative; P = 0.002] and type of operation (HR = 5.075 for exploration vs. resection; P = 0.001) as significant to survival.

Conclusions

Although R0 resection can be achieved in only a minority of patients, these patients have a reasonable chance of longterm survival. The last decade has seen a significant rise in rates of resectability of Klatskin''s tumour at specialty centres.     

Quality of life and survival analysis of patients undergoing transarterial chemoembolization for primary hepatic malignancies: a prospective cohort study

Introduction

Transarterial chemoembolization (TACE) is indicated for primary hepatic tumours when resection or local ablation are not feasible. Patients undergoing TACE have a better survival than best supportive therapy. However, there is paucity of prospective studies on the quality of life (QOL) after TACE for primary hepatic malignancies, especially in the Western world.

Purpose

The primary aim of the present study was to determine if TACE impacts on the QOL of patients affected by primary hepatic tumours, and to assess treatment efficacy in a prospective cohort of patients treated at a tertiary Canadian university medical centre.

Methods

From September 2005 to December 2010, 48 candidates for TACE underwent at least one TACE session. Data on their QOL, tumour response, serum alpha fetoprotein (AFP) and survival were prospectively collected every 3–4 months.

Results

The overall QOL of patients undergoing TACE did not decline during the first 12 months after treatment. A decline was observed in the physical health domain after the third TACE that coincided with the increasing size of the largest tumour and a rise in the serum AFP levels. Psychological, social and environmental domains remained stable throughout the treatment period. Multivariate analysis revealed that tumour focality, AFP levels and model of end-stage liver disease (MELD) scores were associated with long-term survival (P = 0.001, P = 0.01, P = 0.02, respectively). The overall survival at 12, 36 and 48 months were 72%, 28% and 12%, respectively.

Conclusion

TACE is an effective palliative intervention for unresectable and non-ablatable primary liver tumours without affecting the QOL of patients even when repeated interventions are performed.     

Preoperative computed tomography measurements of pancreatic steatosis and visceral fat: prognostic markers for dissemination and lethality of pancreatic adenocarcinoma

Background

Increased visceral fat and pancreatic steatosis promote lymphatic metastases and decreased survival in patients with pancreatic adenocarcinoma after pancreatoduodenectomy (PD).

Objectives

We aim to determine the utility of preoperative computed tomography (CT) measurements of pancreatic steatosis and visceral fat as prognostic indicators in patients with pancreatic adenocarcinoma.

Methods

High-resolution CT scans of 42 patients undergoing PD for pancreatic adenocarcinoma were reviewed. Attenuation in CT of the pancreas, liver and spleen were measured in Hounsfield units and scored by two blinded investigators. Perirenal adipose tissue was measured in mm.

Results

Lymphatic metastases were present in 57% of patients. Age, gender, tumour size and margin status were similar in patients with and without nodal metastases. Node-positive patients had increased visceral but not subcutaneous fat pads compared with node-negative patients and decreased CT attenuation of the pancreatic body and tail and liver. Node-positive patients stratified by visceral adiposity (≥10 mm vs. <10 mm) demonstrated poorer survival (7 ± 1 months vs. 16 ± 2 months; P < 0.01).

Conclusions

In resected pancreatic adenocarcinoma, increased pancreatic steatosis and increased visceral fat stores are associated with lymphatic metastases. Furthermore, increased visceral fat is associated with abbreviated survival in patients with lymphatic metastases. Hence, increased visceral fat may be a causative factor of abbreviated survival and serves a prognostic role in patients with pancreatic malignancies.     

A diagnostic paradigm for resectable liver lesions: to biopsy or not to biopsy?

Background:

Despite a growing body of evidence reporting the deleterious mechanical and oncological complications of biopsy of hepatic malignancy, a small but significant number of patients undergo the procedure prior to specialist surgical referral. Biopsy has been shown to result in poorer longterm survival following resection and advances in modern imaging modalities provide equivalent, or better, diagnostic accuracy.

Methods:

The literature relating to needle-tract seeding of primary and secondary liver cancers was reviewed. MEDLINE, EMBASE and the Cochrane Library were searched for case reports and series relating to the oncological complications of biopsy of liver malignancies. Current non-invasive diagnostic modalities are reviewed and their diagnostic accuracy presented.

Results:

Biopsy of malignant liver lesions has been shown to result in poorer longterm survival following resection and does not confer any diagnostic advantage over a combination of non-invasive imaging techniques and serum tumour markers.

Conclusions:

Given that chemotherapeutic advances now often permit downstaging and subsequent resection of ‘unresectable’ disease, the time has come to abandon biopsy of solid lesions outside the setting of a specialist multi-disciplinary team meeting (MDT).     

Evaluation of peri-operative chemotherapy using a prognostic nomogram for survival after resection of colorectal liver metastases

Introduction:

Nomograms are statistical tools designed to predict outcomes. This study evaluates the effects of peri-operative chemotherapy on the accuracy of a prognostic nomogram for disease-specific survival (DSS) after resection of colorectal liver metastases (CRLM) established at Memorial-Sloan Kettering Cancer Center (MSKCC).

Methods:

An external cohort of 203 patients who underwent resection of CRLM between 1996 and 2006 was used to assess the nomogram.

Results:

After median follow-up of 30.4 months (range 0.33–150), Kaplan–Meier (KM) estimates for 3-, 5- and 8-year post-resection DSS were 56%, 41%, and 32%, respectively; similar to nomogram-predicted probabilities for DSS. The concordance index for the nomogram was higher (0.602) than for the Fong colorectal risk score (CRS; 0.533). KM DSS was longer for patients (n= 50) treated with at least 6 months of peri-operative irinotecan or oxaliplatin compared with all other patients (median 66 vs. 40 months, P= 0.06). KM DSS was greater than nomogram predicted DSS for treated patients and less than nomogram predicted DSS for all other patients.

Conclusions:

The CRLM nomogram was validated by an external cohort and more accurately predicted post-resection survival than the commonly used CRS. Differences in observed and nomogram-predicted survival may reflect the effect of treatment factors, such as peri-operative chemotherapy.     

Concomitant dysregulation of microRNAs miR-151-3p and miR-126 correlates with improved survival in resected cholangiocarcinoma

Background

MicroRNAs (miRNAs) are small non-coding genes which become dysregulated in cancer and may predict survival. The role of miRNAs in outcomes in cholangiocarcinoma (CC) has not been reported.

Methods

RNA was extracted from 32 resected CCs along with adjacent uninvolved bile duct epithelium. A total of 43 miRNAs were quantified using NanoString™. Clinicopathologic characteristics and outcomes were captured and compared. Overall survival curves were created using the Kaplan–Meier method; factors, including miRNA expression, were compared by log-rank, chi-squared or Cox regression analyses.

Results

Absolute expression of each miRNA was compared with overall survival after excluding perioperative deaths (n= 3). One upregulated (miR-151-3p; P= 0.003) and one downregulated (miR-126; P= 0.023) miRNA in resected CC relative to adjacent normal bile duct epithelium correlated with survival on univariate analysis. Clinical factors and these miRNAs were compared. Dysregulated miR-151-3p and miR-126, respectively, were the only factors that correlated with improved overall survival [41.5 months vs. 12.3 months (P= 0.002) and 21.9 months vs. 15.1 months (P= 0.02), respectively]. In eight patients, both miRNAs were dysregulated. In the remainder, only one or neither showed dysregulation. Concomitant dysregulation correlated with the best overall survival (58.7 months vs. 15.1 months; P < 0.000; n= 8); clinicopathologic factors in these groups were otherwise similar.

Conclusions

In resected CC, the concomitant dysregulation of both miR-151-3p and miR-126 was the factor related to the greatest improvement in overall survival. Further analysis of the targets of these miRNAs may yield potential therapeutic targets or prognostic biomarkers.