The Expression of Both Peroxisome Proliferator-Activated Receptor Delta and Cyclooxygenase-2 in Tissues Is Associated with Poor Prognosis in Colorectal Cancer Patients

Background

The role of peroxisome proliferator-activated receptor delta (PPAR ??) in the development and progression of colorectal cancer (CRC) remains controversial.

Aims

We investigated the impact of PPAR ?? expression in tissues on liver metastasis of CRC.

Methods

We analyzed samples of primary CRC and matched normal adjacent tissues from 52 patients for the expression of PPAR ??, cyclooxygenase (COX)-2, vascular endothelial growth factor (VEGF)-A, and CXC chemokine receptor 4 (CXCR4). Correlations of the molecules expressions with clinical characteristics and prognosis of patients were studied.

Results

The number of patients positive for PPAR ??, COX-2, CXCR4, and VEGF-A was 25, 33, 18, and 19, respectively. Among the PPAR ?? (+)/COX-2 (+), PPAR ?? (?)/COX-2 (+), PPAR ?? (+)/COX-2 (?), and PPAR ?? (?)/COX-2 (?) patient groups, PPAR ?? (+)/COX-2 (+) patients had the highest incidence of liver metastasis (p < 0.01). PPAR ?? (+)/COX-2 (+) expression was a significant independent prognostic factor (HR = 7.108, 95% CI 1.231?C41.029, p = 0.0283) by Cox proportional analysis. PPAR ?? (+)/COX-2 (+) patients had the highest positivity for CXCR4 or VEGF-A in tissues (p < 0.01). Among the patients in the CXCR4 (+)/VEGF-A (+), CXCR4 (+)/VEGF-A (?), CXCR4 (?)/VEGF-A (+), and CXCR4 (?)/VEGF-A (?) groups, CXCR4 (+)/VEGF-A (+) patients had the highest incidence of liver metastasis (p < 0.01).

Conclusions

The expression of both PPAR ?? and COX-2 in tissues may lead to liver metastasis and consequent poor prognosis in CRC patients.     

New invasive patterns as a prognostic factor for superficial esophageal cancer

Background

Prognostic factors for superficial esophageal cancer cannot be limited to such factors as lymph node metastasis (N factor), depth of tumor invasion (T factor), and genetic alterations. The purpose of this study was to examine whether invasive growth patterns of tumors, such as infiltrative growth pattern c (INFc) and budding, represent new useful prognostic factors for superficial esophageal cancer.

Methods

We investigated 87 cases of superficial esophageal cancer in patients treated with radical surgery. First, the invasive growth pattern of the tumor was pathologically evaluated based on the traditional infiltrative growth pattern (INF) classification. Next, new INF criteria were proposed, and the invasive pattern was re-evaluated. We also investigated budding (Bud) in the stroma of the invasive frontal lesion.

Results

When the patients were divided into two groups, with and without an INFc component, the group with an INFc component had a poorer outcome than the group without an INFc component. When the group with an INFc component was defined as ??new INFc??, new INFc was correlated with the T factor (p = 0.006) and the ly factor (lymphatic invasion) (p = 0.041). Bud was correlated with the T factor (p = 0.001), the N factor (p = 0.030), and new INFc (p < 0.001). An analysis of survival revealed new INFc (p = 0.002) and Bud (p = 0.006) to be prognostic factors. The survival of the group with new INFc(+)/Bud(+) was poorer than that with new INFc(?)/Bud(?) (p = 0.007).

Conclusions

New INFc and Bud, which represent new invasive patterns, were prognostic factors for superficial esophageal cancer.     

Quality Improvement Measures Lead to Higher Surveillance Rates for Hepatocellular Carcinoma in Patients with Cirrhosis

Background

Cirrhosis is a major risk factor associated with the development of hepatocellular carcinoma (HCC). The American Association for the Study of Liver Diseases recommends surveillance for HCC in cirrhosis patients with ultrasound every six months. However, various studies suggest that surveillance rates in actual practice are quite low.

Aim

The aims of this study were to evaluate the effectiveness of implementing quality improvement (QI) measures in increasing the rate of HCC surveillance among patients in a tertiary care facility.

Methods

Patients with cirrhosis were prospectively enrolled into a chronic disease management program, which integrates nursing-based protocols with automatic reminders when patients are due for surveillance. Patients enrolled in this program between March 2010 and April 2011 were compared to a prior cohort in 2008–2009. The primary endpoint was the receipt of at least one abdominal imaging study performed for the purposes of surveillance during the study period.

Results

Of the 355 patients enrolled, 331 (93 %) had imaging performed for HCC surveillance, compared to 119/160 (74 %) patients in the previous cohort (p < 0.001). Chart review revealed the most common reasons for failure to undergo surveillance were patients’ lack of insurance and lack of follow-up on studies ordered at outside institutions. Six patients were diagnosed with HCC during the study period, of which three were at early stage.

Conclusions

Implementation of QI measures incorporating automatic reminders of surveillance status for providers can significantly increase the rate of HCC surveillance among cirrhosis patients.     

Value of Highly Sensitive Fucosylated Fraction of Alpha-Fetoprotein for Prediction of Hepatocellular Carcinoma Recurrence After Curative Treatment

Background

The fucosylated fraction of alpha-fetoprotein (AFP-L3) has been used as a diagnostic marker for hepatocellular carcinoma (HCC). Recently, a highly sensitive immunoassay using an on-chip electrokinetic reaction and separation by affinity electrophoresis (micro-total analysis system; μTAS) has been developed.

Aim

The aim of this study was to investigate the relationship between changes in the serum AFP-L3 level measured by μTAS assay and recurrence of HCC after curative treatment.

Methods

A total of 414 HCC patients who met the Milan criteria and underwent hepatectomy or radiofrequency ablation were investigated prospectively for the relationship between HCC recurrence and values of tumor markers.

Results

There were significant differences in recurrence-free survival between groups with and without AFP-L3 elevation measured before and after treatment (p = 0.024 and p = 0.001 for before and after treatment, respectively). Multivariate analysis revealed that AFP-L3 status (p = 0.002) measured 1 month after treatment was a significant independent predictor of HCC recurrence after curative treatment.

Conclusions

Elevation of the serum AFP-L3 level before treatment is a predictor of HCC recurrence, and sustained elevation of the AFP-L3 level after treatment is an indicator of HCC recurrence. Repeated measurement of μTAS AFP-L3 should be performed for surveillance of HCC recurrence after curative treatment.     

Clinicopathological features of ulcerative colitis-associated colorectal cancer pointing to efficiency of surveillance colonoscopy in a large retrospective Japanese cohort

Purpose

Cancer surveillance has been conducted in patients with ulcerative colitis (UC), and the number of operative cases of ulcerative colitis-associated colorectal cancer (UC-CRC) has been increasing. The aim of this study was to clarify the clinicopathological features and prognoses of UC-CRC patients and the relationship between surveillance colonoscopy and UC-CRC.

Methods

The clinical records of 1,274 UC patients who required surgery between 1984 and 2010 at a single institution were reviewed retrospectively. Of these, 83 patients had CRC (107 sections). All cases were extracted from the database, along with their clinicopathological data.

Results

The 5-year survival rate of the UC-CRC group was 89 %. The 5-year survival rate was 100 % in stages 0 and II, 96 % in stage I, 56 % in stage III, and 0 % in stage IV. Surveillance colonoscopy was performed for 40 of the 83 patients. Of 40 patients, 30 with UC who underwent surveillance colonoscopies and 22 of 43 patients without surveillance colonoscopies were in stages 0 to I (P?=?0.04).

Conclusion

The number of UC-CRC patients who are diagnosed by surveillance colonoscopy is increasing, and many of them are detected in the very early stages (stages 0 or I). Thus, the survival rate of UC-CRC is better than before. Surveillance colonoscopy proofs efficient as CRC are detected in earlier stages.     

The prevalence and risk factors for atrioesophageal fistula after percutaneous radiofrequency catheter ablation for atrial fibrillation: the Canadian experience

Purpose

Atrioesophageal fistula (AEF) is an infrequent complication of radiofrequency (RF) ablation for atrial fibrillation (AF). The aim of this study was to determine the prevalence and operator-dependent factors associated with AEF using a nationwide survey of electrophysiologists (EP).

Methods

Thirty-eight EPs performing AF ablation between 2008 and 2012 were invited to complete a web-based questionnaire assessing the prevalence and factors associated with AEF.

Results

Responses were obtained from 25 EPs (68 %) accounting for 7,016 AF ablations. Five cases of proven AEF (0.07 %) were reported. Operators who reported AEF [AEF (+)] more often used general anesthesia (GA) [90 % AEF (+) vs. 44 % AEF (?), p?=?0.046]. AEF (+) operators were also more likely to be users of the non-brushing technique in the posterior wall of the LA [5 (100 %) AEF (+) vs. 5 (25 %) AEF (?), p?=?0.005]. The combined usage of GA and non-brushing technique during LA posterior wall ablation had a strong association with AEF (+) operators [4 (80 %) AEF (+) vs. 2 (10 %) AEF (?), p?=?0.002]. There was a trend towards higher maximal RF energy setting in the posterior wall [47.4 + 7.6 AEF (+) vs. 40.2 + 8 AEF (?), p?=?0.09]. Other procedure parameters were similar.

Conclusions

The reported prevalence of AEF among Canadian AF ablators is 0.07 %. AEF was associated with high mortality. The use of GA and non-brushing movements during posterior wall ablation were two factors associated with AEF.     

Familial clustering of hepatocellular carcinoma in HBsAg-positive patients in the United States

Purpose

The impact of familial clustering of hepatocellular carcinoma (HCC) in hepatitis B virus (HBV)-infected persons in a low HBV endemic area was investigated.

Methods

Four hundred thirteen HBsAg-positive patients, 173 with HCC and 240 without HCC, were subgrouped into those with or without a family history of HCC and analyzed for risk factors associated with HCC development. In families with HCC clustering, the ages of HCC onset in parents and siblings were compared.

Results

Forty-four of 173 (25.4 %) HCC patients, all of Asian descent, had 82 other blood relatives with HCC. Of these, 69 (84.1 %) were first-degree relatives. Compared to HCC patients without HCC family history, male HCC patients with family history developed HCC at a younger age than either their mothers or fathers with HCC (45.2 ± 10.3 years vs. 63.0 ± 6.8 years, p < 0.001 and 41.2 ± 14.8 years vs. 60.5 ± 5.5 years, p = 0.001, respectively); however, this was not observed in female HCC patients. In mothers of index HCC cases, 22/26 (84.6 %) tested were HBsAg positive and 14 (63.6 %) had HCC; in fathers, 11/21 (52.4 %) tested were HBsAg positive and 10 (90.9 %) had HCC. By multivariate analysis, independent risk factors for HCC development included family history (OR = 2.58, p = 0.05), male gender (OR = 3.23, p = 0.03), cirrhosis (OR = 2.4, p = 0.04), Child-Pugh classification (OR = 7.62, p = 0.004), AFP per log₁₀ increase (OR = 1.68, p = 0.01), precore mutation (OR = 3.77, p = 0.003), and basal core promoter mutation (OR = 8.33, p < 0.001).

Conclusions

HBsAg-positive male HCC patients presented at a younger age than their parents with HCC. In adult patients with an HCC family history, HCC surveillance should begin at the time of the initial clinic encounter.     

High-sensitivity Lens culinaris agglutinin-reactive alpha-fetoprotein assay predicts early detection of hepatocellular carcinoma

Background

Prognosis of patients with hepatocellular carcinoma (HCC) remains poor because HCC is frequently diagnosed late. Therefore, regular surveillance has been recommended to detect HCC at the early stage when curative treatments can be applied. HCC biomarkers, including Lens culinaris agglutinin-reactive fraction of alpha-fetoprotein (AFP-L3), are widely used for surveillance in Japan. A newly developed immunoassay system measures AFP-L3 % with high sensitivity. This retrospective study aimed to evaluate clinical utility of high-sensitivity AFP-L3 (hs-AFP-L3) as a predictor of early stage HCC in surveillance at a single site.

Methods

Of consecutive 2830 patients in the surveillance between 2000 and 2009, 104 HCC-developed and 104 non-HCC patients were selected by eligibility criteria and propensity score matching. Samples were obtained from the HCC patients who had blood drawn annually for 3 years prior to HCC diagnosis.

Results

In the present study, hs-AFP-L3 was elevated 1 year prior to diagnosis in 34.3 % of patients. The survival rate of patients with the hs-AFP-L3 ≥ 7 % at 1 year prior to diagnosis was significantly lower than that of patients with hs-AFP-L3 < 7 %.

Conclusions

Elevation of hs-AFP-L3 was early predictive of development of HCC even at low AFP levels and in absence of ultrasound findings of suspicious HCC. The hs-AFP-L3 should be added to surveillance programs with US because elevated hs-AFP-L3 may be a trigger to perform enhanced imaging modalities for confirmation of HCC.     

Thrombocytosis and Hepatocellular Carcinoma

Background

Thrombocytopenia has been reported to be both a risk factor for hepatocellular carcinoma (HCC) development as well as a prognostic factor. Many HCCs also occur in presence of normal platelets.

Aim

To examine a cohort of HCC patients with associated thrombocytosis.

Methods

Records were examined of a cohort of 634 biopsy-proven and randomly presenting HCC patients without thrombocytopenia.

Results

In the total cohort, 52 patients were identified with thrombocytosis (platelet levels >400 × 10⁹/L) and compared with 582 patients with normal platelet values. The average tumor sizes were 13.1 versus 8.8 cm (p < 0.0001), and their total average bilirubin levels were 0.9 versus 1.5 (p = 0.02), comparing thrombocytosis patients versus normal platelet count HCC patients. These differences were even more pronounced in patients with HCC sizes >5 cm. Thrombocytosis patients were younger and had less cirrhosis, but similar percent with hepatitis B or C or alcohol consumption.

Conclusion

Thrombocytosis in association with HCC occurs in patients with larger tumor sizes and better liver function.     

Survival of infiltrative hepatocellular carcinoma patients with preserved hepatic function after treatment with transarterial chemoembolization

Purpose

Transarterial chemoembolization (TACE) is highly effective and safe therapeutic modality for unresectable hepatocellular carcinoma (HCC). However, the role of TACE for infiltrative HCC has never been elucidated owing to the concern about hepatic failure and subsequent mortality after the procedure. In this study, we aimed to document whether patients with infiltrative HCC would benefit from TACE.

Methods

Child-Pugh class A/B patients who were newly diagnosed as infiltrative HCC and treated with curative-intent TACE were enrolled. All radiological images were reviewed by a radiologist with more than 20 years of experience in TACE.

Results

Among 1,184 patients newly diagnosed as HCC, 233 (19.7 %) had infiltrative-type tumors and 128 (54.9 %) underwent curative-intent TACE. Although the median overall survival was 5.4 months (IQR 3.1–13.9 months) and 16 (12.5 %) patients had experienced significant complications, 19 (15.9 %) patients survived more than 2 years after the first diagnosis. In multivariable analysis, age >60 years old (HR 0.54, 95 % CI 0.31–0.92), Child-Pugh class A (HR 0.48, 95 % CI 0.30–0.76), and a major PVT without parasitic supply (HR 0.66, 95 % CI 0.44–0.99) were independent favorable prognostic factors. Development of significant complication after TACE was a significant hazard factor of survival (HR 1.99, 95 % CI 1.09–3.62).

Conclusions

In carefully selected patients with preserved hepatic function and good performance, TACE may achieve long-term survival of infiltrative HCC patients with major PVT without parasitic supply. However, the risk of morbidity and immediate mortality after TACE should be considered to select subjects for the procedure.     

Characteristics and Management of Patients with Chronic Hepatitis B in an Integrated Care Setting

Background

Few population-based studies have described characteristics and management of patients with chronic hepatitis B (CHB) in the USA.

Methods

We retrospectively studied adults with CHB in the Northern California Kaiser Permanente Medical Care Program (KPNC) from July 2009 to December 2010 (n = 12,016). Laboratory tests, treatment patterns, and hepatocellular carcinoma (HCC) surveillance were ascertained during a “recent” 18-month study window (July 2009–December 2010), or as “ever” based on records dating to 1995.

Results

The mean age was 49 years; 51 % were men, 83 % Asian, and 87 % KPNC members >5 years. Overall, 51 % had ≥1 liver-related visit, 14 % with gastroenterology or infectious disease specialists, and 37 % with primary care providers (PCP) only. Less than 40 % of patients had both hepatitis B virus (HBV) DNA and ALT testing conducted recently, while 56 % of eligible patients had received HCC surveillance. Recent laboratory testing and HCC surveillance were more frequent in patients seen by a specialist versus PCP only (90 vs. 47 % and 92 vs. 73 %, respectively, p values <0.001). During the study period, 1,649 (14 %) received HBV treatment, while 5 % of untreated patients had evidence of treatment eligibility. Among 599 patients newly initiated on HBV therapy, 76 % had guideline-based indications for treatment.

Conclusions

Most patients initiated on HBV treatment met eligibility, and very few patients with evidence of needing treatment were left untreated. However, monitoring of ALT and HBV DNA levels, as well as HCC surveillance, were not frequent, underestimating the proportion of patients that warranted HBV therapy. Viral monitoring and cancer surveillance are therefore important targets for improving the scope of CHB care in the community setting.     

Ultrasound surveillance for early detection of hepatocellular carcinoma among patients with chronic hepatitis C

Background and aims

Ultrasonography is the most frequently used modality in surveillance for HCC among patients with chronic hepatitis C. However, the optimal surveillance interval is still controversial and the usefulness of supplementary tumor marker determination has not been confirmed.

Methods

A total of 243 cases of naive HCC were detected among 1,431 patients with chronic hepatitis C under outpatient-based surveillance. The mode of HCC detection, including ultrasound surveillance interval, was retrospectively examined and the relation between the interval and detected tumor size was analyzed. Tumor volume doubling time was estimated from exponential increase in serum tumor marker levels when applicable.

Results

HCC was first detected by ultrasonography in 221 patients. Ultrasound surveillance interval, ranging between 2 and 8 months, was not correlated with the size of tumor at detection. Patients with cirrhosis were likely to be surveyed at shorter intervals. The size of tumor exceeded 30 mm only in three (1.4%) cases. They were all positive for a biomarker and the estimated tumor doubling time was short. In 14 cases, HCC was first detected by CT indicated by abnormal rise in tumor marker levels despite negative ultrasound findings. In the remaining eight cases, ultrasonography had been replaced by CT as surveillance modality because of excessive obesity or coarseness of liver parenchyma.

Conclusions

Ultrasound surveillance at 6-month intervals was appropriate in general for the detection of HCC at a size smaller than 30 mm. However, in patient with established cirrhosis, more frequent screening would be needed to detect tumors of the same size.     

Laparoscopic liver resection for treating recurrent hepatocellular carcinoma

Background

It is still unknown whether laparoscopic liver resection is suitable for recurrent hepatocellular carcinoma (HCC) after previous curative hepatic resection.

Method

The perioperative outcomes of 40 patients treated with second surgery for recurrent HCC by partial hepatectomy were studied retrospectively. The second surgery was performed under laparotomy in 20 patients (laparotomy group) and under laparoscopy in 20 patients (laparoscopy group).

Results

Intraoperative blood loss (p < 0.0001) and the incidence of postoperative complications (p = 0.0004) were lower in the laparoscopy group than in the laparotomy group. The incidence rates of surgical site infection and intractable ascites were significantly higher in the laparotomy group than in the laparoscopy group (p = 0.0202, p = 0.0436, respectively). The proportion of patients classified as Clavien grade IIIa was higher in the laparotomy group than in the laparoscopy group (p = 0.0033). The duration of the postoperative hospital stay was significantly shorter in the laparoscopy group than in the laparotomy group (p < 0.0001).

Conclusions

Postoperative morbidity has been decreased by the introduction of laparoscopic liver resection in patients with recurrent HCC after curative hepatic resection. As a result, the duration of the postoperative stay is shorter.     

A non-smooth tumor margin in the hepatobiliary phase of gadoxetic acid disodium (Gd-EOB-DTPA)-enhanced magnetic resonance imaging predicts microscopic portal vein invasion, intrahepatic metastasis, and early recurrence after hepatectomy in patients with hepatocellular carcinoma

Background

The value of the hepatobiliary phase of gadoxetic acid disodium (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) in patients with hepatocellular carcinoma (HCC) has not been evaluated in detail.

Methods

Between 2008 and 2009, 61 patients with HCC within the Milan criteria underwent Gd-EOB-DTPA-enhanced MRI and hepatectomy. The tumor margin was determined preoperatively based on hepatobiliary phase images. Microscopic portal vein invasion (MPVI), intrahepatic metastasis (IM), and recurrence of HCC within 1 year after hepatectomy were evaluated in 24 patients with non-smooth margins at the periphery of the tumor and 37 patients with smooth margins.

Results

The number of patients with MPVI and IM of HCC was significantly higher among those with non-smooth margins (42 and 38%, respectively) than among those with smooth margins (3%; p = 0.0002 and 5%; p = 0.0042, respectively). A non-smooth margin was identified as a significant predictor of MPVI (odds ratio 18.814, p = 0.024) and IM (odds ratio 6.498, p = 0.036) of HCC on multivariate analysis. Furthermore, a non-smooth margin was identified as a significant predictor of recurrence within 1 year after hepatectomy (odds ratio 4.306, p = 0.04) on multivariate analysis.

Conclusions

A non-smooth tumor margin in the hepatobiliary phase of Gd-EOB-DTPA-enhanced MRI is useful to predict MPVI, IM, and early recurrence of HCC after hepatectomy.     

Pre-S Mutation Is a Significant Risk Factor for Hepatocellular Carcinoma Development: A Long-Term Retrospective Cohort Study

Background

Several cross-sectional studies have shown an association between pre-S mutation and hepatocellular carcinoma (HCC).

Aims

We aim to verify whether pre-S mutation represents a risk for HCC development in a longitudinal way.

Methods

A total of 195 patients with chronic HBV infection [age: 43.7 ± 10.8 years, males: 141 (72.3 %), genotype C: 195 (100 %), hepatitis B e antigen (HBeAg) positive: 109 (55.9 %), cirrhosis: 79 (40.5 %), and pre-S mutation positive: 44 (22.6 %)] were followed up for a median of 7.2 years (range 1.0–7.8 years).

Results

HCC developed in 24 patients during follow-up. The 1-, 3-, and 5-year cumulative incidences of HCC were 0.5, 4.9, and 10.4 %, respectively. Patients with pre-S mutation had significantly higher 5-year cumulative incidences of HCC than those without (26.5 vs. 5.7 %, p < 0.001) and showed higher hazard ratio for HCC [3.04 (95 % CI 1.24–7.42), p = 0.015, adjusted for age, gender, HBeAg, cirrhosis and baseline HBV DNA level]. Notably, in patients aged ≥50 years, the 5-year cumulative incidences of HCC in patients with pre-S mutation were considerably high (58.3 %), compared to those without (16.1 %, p < 0.001).

Conclusions

Patients with pre-S mutations had higher incidence of HCC during follow-up, especially in aged patients. Patients with pre-S mutations, especially older ones, may require careful attention to HCC development.     

Hepatocellular carcinoma 20 mm or smaller in cirrhosis patients: early magnetic resonance enhancement by gadoxetic acid compared with gadopentetate dimeglumine

Purpose

To evaluate the differences in enhancement pattern of hepatocellular carcinoma (HCC) 20 mm or smaller and enhancement effects of hepatic vessels on early dynamic contrast-enhanced magnetic resonance imaging (MRI) obtained with gadoxetic acid and gadopentetate dimeglumine in the same patients with cirrhosis.

Methods

We reviewed MR images using gadoxetic acid and gadopentetate dimeglumine in the same 34 patients with 42 histologically confirmed HCCs (median diameter, 14.5 mm). The percentage enhancements (PEs) of HCC, the hepatic artery and portal vein and relative contrasts (RCs) between HCC and the liver were calculated and analyzed statistically.

Results

The PEs of HCC, the hepatic artery and portal vein were significantly lower for gadoxetic acid in comparison with gadopentetate dimeglumine in the arterial phase (p = 0.0256 for HCC, p < 0.0001 for hepatic artery) and portal phase (p < 0.0001 for HCC, portal vein). The RC between HCC and the liver was significantly lower for gadoxetic acid in comparison with gadopentetate dimeglumine in the arterial phase (p = 0.0422), but was not significantly different in the portal phase (p = 0.1133). Forty-one of the 42 (97.62 %) nodules showed arterial hypervascularization. Of these, 31 (75.61 %) nodules were hypointense in the portal phase for gadoxetic acid, and 22 (53.66 %) were hypointense for gadopentetate dimeglumine (p = 0.038).

Conclusions

Compared with gadopentetate dimeglumine, gadoxetic acid-enhanced MRI demonstrated a different enhancement pattern of inferior arterial enhancement and was more rapidly hypointense in the portal phase for HCC. It showed markedly lower enhancement for hepatic artery and portal vein in the patients with cirrhosis.     

Ultrasound Elastography for Fibrosis Surveillance Is Cost Effective in Patients with Chronic Hepatitis C Virus in the UK

Background

Chronic hepatitis C (HCV) is a significant risk factor for cirrhosis and subsequently hepatocellular carcinoma (HCC). HCV patients with cirrhosis are screened for HCC every 6 months. Surveillance for progression to cirrhosis and consequently access to HCC screening is not standardized. Liver biopsy, the usual test to determine cirrhosis, carries a significant risk of morbidity and associated mortality. Transient ultrasound elastography (fibroscan) is a non-invasive test for cirrhosis.

Purpose

This study assesses the cost effectiveness of annual surveillance for cirrhosis in patients with chronic HCV and the effect of replacing biopsy with fibroscan to diagnose cirrhosis.

Method

A Markov decision analytic model simulated a hypothetical cohort of 10,000 patients with chronic HCV initially without fibrosis over their lifetime. The cirrhosis surveillance strategies assessed were: no surveillance; current practice; fibroscan in current practice with biopsy to confirm cirrhosis; fibroscan completely replacing biopsy in current practice (definitive); annual biopsy; annual fibroscan with biopsy to confirm cirrhosis; annual definitive fibroscan.

Results

Our results demonstrate that annual definitive fibroscan is the optimal strategy to diagnose cirrhosis. In our study, it diagnosed 20 % more cirrhosis cases than the current strategy, with 549 extra patients per 10,000 accessing screening over a lifetime and, consequently, 76 additional HCC cases diagnosed. The lifetime cost is £98.78 extra per patient compared to the current strategy for 1.72 additional unadjusted life years. Annual fibroscan surveillance of 132 patients results in the diagnosis one additional HCC case over a lifetime. The incremental cost-effectiveness ratio for an annual definitive fibroscan is £6,557.06/quality-adjusted life years gained.

Conclusion

Annual definitive fibroscan may be a cost-effective surveillance strategy to identify cirrhosis in patients with chronic HCV, thereby allowing access of these patients to HCC screening.     

Factors predicting survival after post-transplant hepatocellular carcinoma recurrence

Background

Although factors associated with an increased risk of recurrence after liver transplantation for hepatocellular carcinoma (HCC) have been extensively studied, the history of patients with a post-transplant recurrence is poorly known.

Methods

Patients experiencing a post-transplant HCC recurrence from 1996 to 2011 in two transplant programs were included. Demographic, transplant, and post-recurrence variables were assessed.

Results

Thirty patients experienced an HCC recurrence–22 men and 8 women with a mean age of 55 ± 6 years. Sixteen (53 %) were outside the Milan criteria at the time of transplantation. Most recurrences (60 %) appeared within the first 18 months after transplantation, ranging between 1.7 and 109 months (median 14.2 months). Mean post-recurrence survival was 33 ± 31 months. On univariate analysis, total tumor volume (TTV; p = 0.047), microvascular invasion (p = 0.011), and time from transplant to recurrence (p = 0.001) predicted post-recurrence survival. On multivariate analysis, both time from transplant to recurrence (p = 0.001) and history of rejection (p = 0.043), but not the location of the recurrence or the type of recurrence treatment, predicted post-recurrence survival.

Conclusion

This study suggests that patients with early post-transplant HCC recurrence have worse outcomes. Those with a history of graft rejection have better survivals, possibly due to more active anti-cancer immunity.     

Costs and prolonged length of stay of central venous catheter-associated bloodstream infections (CVC BSI): a matched prospective cohort study

Purpose

Central venous catheter-associated bloodstream infections (CVC BSI) are a common and serious complication among critically ill patients on intensive care units (ICUs), but also result in a financial burden for the health care system. Our aim was to determine the additional costs and length of stay (LOS) of patients with ICU-acquired CVC BSI.

Methods

We used the surveillance method of the German nosocomial infection surveillance system (Krankenhaus Infections Surveillance System, KISS) to find cases of CVC BSI. The associated costs of CVC BSI were estimated as true costs generated within our hospital. We used a matched cohort design, comparing patients with CVC BSI and patients without BSI. The study period was from January to December 2010. Patients were matched by age, sex, and Simplified Acute Physiology Score (SAPS). The LOS in the ICU of control patients needed to be at least as long as that of CVC BSI patients before the onset of CVC BSI.

Results

We matched 40 CVC BSI patients to 40 patients without BSI. The median hospital costs for CVC BSI patients were significantly higher than for patients without BSI (60,445 € vs. 35,730 €; p = 0.006) and the CVC BSI patients stayed longer in the hospital than patients without CVC BSI (44 days vs. 30 days; p = 0.110). The median attributable costs per CVC BSI was 29,909 € (p = 0.006) and the median attributable LOS was 7 days (p = 0.006).

Conclusion

CVC BSI is associated with increased hospital costs and prolonged hospital stay. Hospital management should implement control measurements to keep the incidence of CVC BSI as low as possible.