R0 Liver Resections for Primary Malignant Liver Tumors in the Noncirrhotic Liver: A Diagnosis-Related Analysis

Background Primary liver cancer constitutes an increasingly malignancy in the Western world and one of the leading causes of cancer-related deaths worldwide. The purpose of this study was to evaluate and compare long-term outcomes after R0 resections in noncirrhotic livers for hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). Methods Between April 1998 and May 2006 a total of 102 patients with either ICC (n = 41, group 1) or HCC (n = 61, group 2) in the absence of cirrhosis underwent curative liver resection in our department. Demographic characteristics, operative details, perioperative complications, pathologic findings, tumor recurrence and survival were analyzed. Results Gender (P = 0.007), extent of liver resection (P = 0.036), additional surgical procedures (P < 0.001) and operative morbidity (P = 0.018) differed among the two groups. Following resection, after a median follow-up of 28 months, the calculated 5-year survival was 44% and 40% for ICC and HCC, respectively (P = 0.38). The corresponding recurrence-free survival was 25% for both ICC and HCC (P = 0.66). UICC stage was found to predict overall and recurrence-free survival in both types of tumors. Multifocality in the case of ICC, and tumor differentiation and vascular invasion in the case of HCC, were predictive factors for overall and recurrence-free survival, respectively. In multivariable analyses, vascular invasion for HCC was predictive for overall and recurrence-free survival, whereas in the case of ICC significant differences were detected in the recurrence analysis for multifocality and UICC stage. Conclusions R0 resections for both ICC and HCC result to similar long-term outcomes, which are characterized by good overall and acceptable recurrence-free survival rates.     

Evaluation of UICC TNM classification for pancreatic cancer

Summary Conclusion A different stage grouping of TNM factors can improve the predictivity of the UICC TNM classification for pancreatic cancer. Nevertheless, the Japanese Pancreas Society (JPS) classification maintains a higher prognostic value. Background The use of a reliable staging classification facilitates the evaluation of anticancer treatments and the correct management of patients. The aim of the present study was to evaluate the prognostic value of three modified UICC TNM classifications, obtained by different stage grouping of the UICC TNM factors, comparing their predictivity to the standard UICC and the JPS classifications. Methods Clinical material consisted of 228 patients who underwent resection for pancreatic cancer. The reliability of the classifications was analyzed by the following methods: univariate analysis of stage survival curves; multivariate analysis of each classification after adjusting for grading and radicality; and correlation between the patients' distribution in the stages of each classification and in survival classes. Results The following modfiied UICC classification allowed a better differentiation of stage II and III survival (P=0.08) than standard UICC (p=0.74): stage I: T1N0M0; stage II: T1N1M0/T2N0M0: stage III: T2N1M0/T3 any NM0; stage IV: M1. The JPS classification better discriminated between the different stages (P<0.001). All classifications had an independent prognostic value by multivariate analysis. The correlation between stages and survival classes was higher for the JPS classification than either UICC TNM classification or the modified UICC classifications.     

Comparison of the prognostic value of the 6th and 7th editions of the Union for International Cancer Control TNM staging system in patients with lower esophageal cancer undergoing neoadjuvant chemotherapy followed by surgery

Carcinoma of the esophagus is classified according to the Union for International Cancer Control (UICC) TNM staging system. The 7th edition of the UICC TNM staging system was published in 2009. This is the first study to compare the prognostic value of the TNM 6th and 7th editions in patients with esophageal carcinoma treated with chemotherapy followed by surgery. Two hundred forty‐three patients with esophageal carcinoma were retrospectively selected from two referral centers. All patients received chemotherapy before surgery. Histopathologic data from the resection specimens were retrieved and restaged according to the TNM 7th edition. Disease‐specific survival curves were plotted for depth of tumor invasion (ypT), lymph node status (ypN), and ypTNM stage and then compared. Median follow‐up after surgery was 2.5 years (range 0.2–9 years). Survival analysis using the log‐rank method revealed that there was a significant difference in survival between ypT4 disease and ypT3 disease (P= 0.003), but no difference between ypT0, ypT1, ypT2, and ypT3 categories irrespective of TNM edition used. Survival probability was significantly different between ypN0 and ypN1 (P= 0.001 for TNM 6th and 7th edition), as well as ypN2 and ypN3 (TNM 7th edition, P= 0.004), but not between ypN1 and ypN2 (TNM 7th edition, P= 0.89). Neither the TNM 6th nor 7th edition T staging provides accurate survival probability stratification. However, the advantage of the 7th edition is the introduction of a third tier in survival stratification for patients with nodal involvement.     

Long‐term outcome of a covered vs. uncovered transjugular intrahepatic portosystemic shunt in Budd–Chiari syndrome

Background: The clinical outcome of a covered vs. uncovered transjugular intrahepatic portosystemic shunt (TIPS) for patients with Budd–Chiari syndrome (BCS) is as yet largely unknown. Objectives: To compare patency rates of bare and polytetrafluoroethylene (PTFE)‐covered stents, and to investigate clinical outcome using four prognostic indices [Child–Pugh score, Rotterdam BCS index, modified Clichy score and Model for End‐Stage Liver Disease (MELD)]. Methods: Consecutive patients with BCS who had undergone TIPS between January 1994 and March 2006 were evaluated in a retrospective review in a single centre. Results: Twenty‐three TIPS procedures were performed on 16 patients. The primary patency rate at 2 years was 12% using bare and 56% using covered stents (P=0.09). We found marked clinical improvement at 3 months post‐TIPS as determined by a drop in median Child–Pugh score (10–7, P=0.04), Rotterdam BCS index (1.90–0.83, P=0.02) and modified Clichy score (7.77–2.94, P=0.003), but not in MELD (18.91–17.42, P=0.9). Survival at 1 and 3 years post‐TIPS was 80% (95% CI: 59–100%) and 72% (95% CI: 48–96%). Four patients (25%) died and one required liver transplantation. Conclusions: A transjugular intrahepatic portosystemic shunt using PTFE‐covered stents shows better patency rates than bare stents in BCS. Moreover, TIPS leads to an improvement in important prognostic indicators for the survival of patients with BCS.     

White blood cell recovery after allogeneic hematopoietic cell transplantation predicts clinical outcome

To determine whether outcome after allogeneic hematopoietic cell transplantation (HCT) could be estimated by using peripheral white blood cell count (WBC) as a metric that integrates several aspects of HCT recovery, we conducted a retrospective study of 1,109 adult patients who underwent first allogeneic HCT from 2003 through 2009. WBC at 1–3 months after HCT was categorized as low (<2), normal (2–10), and high (>10 × 10⁹ cells/L). Overall survival (OS) and progression‐free survival (PFS) were lower for patients with low or high WBC at 1–3 months after HCT (P < 0.0001). We developed a predictive three‐group risk model based on the pattern of WBC recovery early after HCT. Five‐year OS was 47, 30, and 15% (P < 0.0001) and 5‐year PFS was 39, 22, and 14% for patients in the three different risk groups (P < 0.0001). The pattern of WBC recovery early after HCT provides prognostic information for relapse, nonrelapse mortality, progression‐free survival, and overall survival. A scoring system based on the trajectory of the WBC in the first 3 months after HCT can effectively stratify patients into three groups with different PFS and OS. If validated, this system could be useful in the clinical management of patients after HCT, and to stratify patients enrolled on HCT clinical trials. Am. J. Hematol. 89:591–597, 2014. © 2014 Wiley Periodicals, Inc.     

Thymidine phosphorylase, dihydropyrimidine dehydrogenase and thymidylate synthase mRNA expression in primary colorectal tumors—correlation to tumor histopathology and clinical follow-up

Aim Evaluation of thymidine phosphorylase (TP), dihydropyrimidine dehydrogenase (DPD), and thymidylate synthase (TS) mRNA levels in formalin-fixed, and paraffin-embedded tissues of patients with colorectal cancer and their prognostic and/or predictive value.Materials and methods Total RNA was isolated from microdissected, formalin-fixed, and paraffin-embedded tissues (controls and tumor) and subjected to quantitative RT-PCR (QRT-PCR) in the LightCycler system. Resulting mRNA levels correlated to tumor histology (n=102) and the clinical follow-up in patients treated by resection alone (n=40) and by resection plus adjuvant 5-FU-based chemotherapy (n=52).Results Correlation to histopathological parameters revealed a significant association between tumor stage and the TP mRNA level (T and N category and UICC) as well as the TP:DPD (T and N category and UICC) and TS:DPD (T category) ratio. In addition, tumor differentiation was correlated to the TS mRNA level and the TS:DPD ratio. Finally, the TS:DPD ratio was a prognostic marker for overall survival in patients receiving resection alone (p=0.032). Moreover, a high TP:DPD ratio (>8.1; p=0.002) and, marginally, low DPD (<8.2; p=0.05) mRNA levels significantly correlated to disease-free survival.Conclusion We present a novel, standardized approach for TP, DPD, and TS mRNA quantification in archival tissue specimens and applied this to a large series of primary colorectal tumors. Correlations to histopathological parameters and clinical follow-up revealed an association of TP, DPD and TS mRNA expression patterns with tumor stage and suggested new prognostic and predictive markers for patients with colorectal cancer.     

Transarterial chemoembolization versus percutaneous microwave coagulation therapy for recurrent unresectable intrahepatic cholangiocarcinoma: Development of a prognostic nomogram

Background:Transarterial chemoembolization(TACE)and percutaneous microwave coagulation therapy(PMCT)are commonly used to treat intrahepatic recurrent liver cancers.However,there is no informa-tion regarding their effectiveness in patients with recurrent intrahepatic cholangiocarcinoma(ICC)after resection.Methods:A total of 275 patients with localized recurrent ICC who received either TACE(n=183)or PMCT(n=92)were studied.A propensity score matching analysis was performed to compare prognostic impact of TACE and PMCT.Prognostic factors for TACE and PMCT were identified respectively.Predictive nomograms for each TACE and PMCT were developed using the Cox independent prognostic factors and were validated in independent patient groups by receiver operating characteristic curves and area under curve values.Results:Both TACE and PMCT provided curativeness in partial patients(5-year overall survival:21.4%and 6.1%,respectively),but TACE provided better survival benefit in both overall patients(hazard ratio[HR]=0.71;95%confidence interval[CI]:0.50–0.97;P=0.034)and propensity score matching analysis(HR=0.69;95%CI:0.47–0.98;P=0.041).Independent prognostic factors for TACE were tumor size>5 cm,poor differentiation,and major resection,whereas poor differentiation,hepatitis B virus infection,cholelithiasis,and lymph node metastasis were identified for PMCT.Both predictive nomograms for TACE and PMCT were validated to be effective with area under curve values of 0.77 and 0.70,respectively.Conclusions:TACE provided better survival benefits compared to PMCT.However,there was a disparity in prognostic factors,suggesting evaluation of the two nomograms may be supportive in modality selection.Further prospective validation studies are required for the results to be applied in clinical medicine.     

Serum DJ-1 as a diagnostic marker and prognostic factor for pancreatic cancer

OBJECTIVE: DJ‐1 is an oncoprotein secreted by cancer cells. Therefore, it might be a diagnostic or prognostic biomarker for pancreatic cancer (PC). METHODS: The study involved 47 patients with PC, 43 with chronic pancreatitis, and 40 healthy subjects. We assayed the serum level of DJ‐1 and the conventional tumor marker carbohydrate antigen 19‐9 (CA 19‐9) to define the diagnostic and prognostic value of DJ‐1 for PC. RESULTS: Serum DJ‐1 level was elevated in patients with PC compared with those with chronic pancreatitis and healthy individuals. The area under the curve (AUC) of serum DJ‐1 was higher than CA 19‐9 (DJ‐1 vs. CA19‐9, 0.8735 ± 0.0356 vs. 0.6647 ± 0.0572 ng/mL), and an 87.5% sensitivity was reached with a combination of serum DJ‐1 and CA19‐9. No association of serum DJ‐1 level with tumor node metastasis (TNM) classification or tumor resectability was found. However, after resection, the median serum DJ‐1 level was decreased from 2.00 to 0.78 ng/mL. In addition, higher serum DJ‐1 was correlated with shorter overall survival as analyzed by both Kaplan–Meier test (P = 0.018) and COX regression analysis (P = 0.013). The median overall survival time of PC patients with serum DJ‐1 level greater than or equal to 2.06 ng/mL was 7.00 ± 1.11 months, whereas that of patients with lower DJ‐1 levels was 13.0 ± 2.5 months. CONCLUSIONS: These findings indicate the potential clinical significance for serum DJ‐1 level to be used for the diagnosis and prognosis prediction of patients with PC.     

Survival analysis of 904 patients with hepatocellular carcinoma in a hepatitis B virus-endemic area

Background and Aim: To investigate the clinical characteristics and survival outcomes of a large cohort of hepatocellular carcinoma (HCC) patients treated at a single institute in a hepatitis B virus (HBV)–endemic area. Methods: Between 2000 and 2003, 904 patients with HCC treated at our institute were enrolled, and followed until 2005. Results: The mean age of the patients was 56 years and 76.3% were HBV‐positive. The 1‐, 2‐, 3‐, and 4‐year survival rates were 53.8%, 40.0%, 31.4%, and 25.7%, respectively. The 4‐year survival rates for Child–Pugh class A patients treated by resection or transarterial chemoembolization (TACE) were 77.3% and 63.2% for those with modified International Union Against Cancer (UICC) stage I or II disease (P = 0.043), and 58.6% and 19.2% for those with modified UICC stage III disease (P < 0.001). In patients with Child–Pugh class A and stage IVa, the median survival times differed between TACE and chemotherapy treatments (6.9 vs 4.0 months, P = 0.003), whereas in patients with stage IVb there was no difference between treatments (8.5 vs 6.1 months, P = 0.173) Serum α‐fetoprotein level, presence of portal vein tumor thrombosis, Child–Pugh class, tumor, node, and metastasis stage, and the number and type of HCC were all related to prognosis. Significant differences in survival curves were observed among the Japanese Integrated Staging scores. Conclusions: The results of this study will be helpful in determining the survival outcomes and treatment strategies for HCC patients in HBV‐endemic areas.     

Prognostic scoring systems for myelodysplastic syndromes (MDS) in a population‐based setting: a report from the Swedish MDS register

The myelodysplastic syndromes (MDS) have highly variable outcomes and prognostic scoring systems are important tools for risk assessment and to guide therapeutic decisions. However, few population‐based studies have compared the value of the different scoring systems. With data from the nationwide Swedish population‐based MDS register we validated the International Prognostic Scoring System (IPSS), revised IPSS (IPSS‐R) and the World Health Organization (WHO) Classification‐based Prognostic Scoring System (WPSS). We also present population‐based data on incidence, clinical characteristics including detailed cytogenetics and outcome from the register. The study encompassed 1329 patients reported to the register between 2009 and 2013, 14% of these had therapy‐related MDS (t‐MDS). Based on the MDS register, the yearly crude incidence of MDS in Sweden was 2·9 per 100 000 inhabitants. IPSS‐R had a significantly better prognostic power than IPSS (P < 0·001). There was a trend for better prognostic power of IPSS‐R compared to WPSS (P = 0·05) and for WPSS compared to IPSS (P = 0·07). IPSS‐R was superior to both IPSS and WPSS for patients aged ≤70 years. Patients with t‐MDS had a worse outcome compared to de novo MDS (d‐MDS), however, the validity of the prognostic scoring systems was comparable for d‐MDS and t‐MDS. In conclusion, population‐based studies are important to validate prognostic scores in a ‘real‐world’ setting. In our nationwide cohort, the IPSS‐R showed the best predictive power.     

Predictors of survival in refractory anemia with ring sideroblasts and thrombocytosis (RARS‐T) and the role of next‐generation sequencing

Refractory anemia with ring sideroblasts and thrombocytosis (RARS‐T) shares overlapping features of myelodysplastic syndromes (MDS) and myeloproliferative neoplasms (MPN). RARS‐T is characterized by SF3B1 and JAK2 mutations and prognosis is considered to be better than MDS but not as good as MPN. The objective of the study was to identify predictors of survival in RARS‐T. We analyzed clinical and laboratory variables in 82 patients and applied a 27‐gene NGS assay to 48 marrow samples obtained at diagnosis. 94% of patients had ≥1 mutations; common mutations being: SF3B1 85%, JAK2V617F 33%, ASXL1 29%, DNMT3A 13%, SETBP1 13% and TET2 10%. In a multivariable survival analysis (n = 82), anemia (P = 0.02) [HB< 10 gm/dl: HR 2.3, 95% CI 1.2–4.6] and abnormal karyotype (P =.01) [HR 6.1, 95% CI 2.7‐13.8] were independently prognostic for inferior survival. In patients with NGS information (n = 48), univariate analysis showed association between poor survival and presence of SETBP1 (P = 0.04) or ASXL1 (P = 0.08) mutations whereas the absence of these mutations (ASXL1wt/SETBP1wt) was favorable (P = 0.04); the number of concurrent mutations did not provide additional prognostication (P = 0.3). We developed a HR‐weighted prognostic model, with 2 points for an abnormal karyotype, 1 point for either ASXL1 and/or SETBP1 mutations, and 1 point for a HB level < 10 gm/dl, which effectively stratified patients into three risk categories; low (0 points), intermediate (1 point) and high (≥2 points), with median survivals of 80, 42 and 11 months respectively (P = 0.01). In summary, we confirm the unique mutational landscape in RARS‐T and provide a novel mutation‐enhanced prognostic model. Am. J. Hematol. 91:492–498, 2016. © 2016 Wiley Periodicals, Inc.     

Carbohydrate antigen 19‐9 is extremely elevated in polycystic liver disease

Background/Aims: Carbohydrate antigen 19‐9 (CA19‐9) is used as a biomarker to differentiate benign from malignant gastrointestinal disorders. We examined the value of CA19‐9 measurement in polycystic livers after observing high CA19‐9 cyst fluid levels in a benign polycystic liver case. Methods: We determined CA19‐9 levels in serum (n=120) and hepatic cyst fluid (n=81), from patients with polycystic livers (n=109) and simple hepatic cysts (n=24). Further, we analysed CA19‐9 expression in normal and polycystic liver tissue (n=17). Results: Cyst fluid CA19‐9 levels from both polycystic livers and simple hepatic cysts were extremely high (median 91 000 U/ml, range 14–15 870 000 U/ml; median 85 000 U/ml, range 332–1 744 000 U/ml respectively). Serum CA19‐9 levels were significantly higher in polycystic liver patients (median 30 U/ml, range 0–1200 U/ml) compared with patients with simple hepatic cysts (median 10 U/ml, range 3–200 U/ml, P=0.0011). Serum CA19‐9 levels correlated with those in cyst fluid (r=0.3979, P=0.0399), polycystic liver volume (r=0.3870, P=0.0025) and the size of the largest cyst (simple cysts group; r=0.5319, P=0.0280). Cyst epithelia showed strong CA19‐9 expression. Evacuation of cyst fluid in four patients resulted in a dramatic decrease in the serum CA19‐9 levels (60–95%). Conclusions: CA19‐9 levels are high in the cyst fluid and serum of polycystic liver disease patients due to production and secretion by cyst epithelia. It does not reflect malignancy in these patients and may be of value as a biomarker for intervention efficiency assessment.     

Prognostic factors and evaluation of a clinical score for predicting survival after resection of colorectal liver metastases

Background: Patient outcome after resection of colorectal liver metastases can be predicted by various prognostic factors. Aims: Development of a model for risk stratification based on analysis of prognostic factors. Methods: Data of 201 patients were collected prospectively and included in a single‐centre trial. A total of 20 factors were analysed as to their influence on recurrence‐free and overall survival. Independent prognostic factors were entered into a model of a clinical risk score. Results: Median recurrence‐free survival reached 24 months for all patients; median overall survival was 50 months. Only a synchronous manifestation of primary colorectal carcinoma and liver metastases, the presence of four or more metastases and a carcino‐embryonic antigen level of 200 ng/ml or more significantly influenced recurrence‐free and overall survival in the multivariate analysis. The derived risk stratification grouped the patients according to the following criteria: low risk, zero prognostic factors (n=112); intermediate risk, one factor (n=74); high risk, two or more factors (n=15). The median recurrence‐free survival for low, intermediate and high risk were 30.0, 23.0 and 11.0 months, respectively; the median overall survival was 94.0, 40.0 and 33.0 months. Compared with the low‐risk group, patients with intermediate risk demonstrated an increased hazard ratio (HR) of 1.57‐fold for recurrence (P=0.018) and 1.91‐fold for mortality (P=0.007). For the high‐risk group, the HR rose significantly to 3.26 for recurrence (P<0.0005) and to 3.10 for mortality (P=0.001). Conclusions: The presented clinical score may allow for patients with colorectal liver metastases to be stratified appropriately and for optimization of their subsequent therapeutic management.     

Prognostic value of 18F‐FDG PET for hepatocellular carcinoma patients treated with sorafenib

Background: Sorafenib (Nexavar) is an orally active multikinase inhibitor that is approved for the treatment of hepatocellular carcinoma (HCC). In this study, we used ¹⁸F‐2‐fluoro‐2‐deoxyglucose (¹⁸F‐FDG) with positron emission tomography (PET) to predict the treatment outcome of sorafenib in patients with advanced HCC. Materials and methods: A total of 29 patients with HCC were included. Baseline ¹⁸F‐FDG PET scans were performed a median of 14 days before sorafenib treatment. Sorafenib was administered orally at a dose of 400 mg twice daily. For statistical analysis, the standardized uptake value (SUV) of the most hypermetabolic lesion was obtained and assigned as the SUVmax for each patient. Results: Among 29 patients, one patient achieved partial remission and 14 patients showed stable disease. The overall survival (OS) and progression free survival (PFS) were 5.1 months [95% confidence interval (CI): 0.0–12.0] and 3.8 months (95% CI: 1.4–6.2). The multivariate analysis of OS showed that four indices, Eastern Cooperative Oncology Group performance status, α‐fetoprotein (AFP) concentration, portal vein thrombosis and SUVmax were significant prognostic factors (P=0.030, P=0.024, P=0.020 and P=0.015 respectively). AFP concentration and SUVmax were independent prognostic factors for PFS, too (P=0.003 and P=0.026 respectively). When the patients were divided into two groups: low SUVmax (n=10; <5.00) and high SUVmax (n=19;≥5.00), the low SUV group showed significantly longer OS and PFS (P=0.023 and P=0.042 respectively). Conclusion: Our study showed that the degree of FDG uptake is an independent prognostic factor in patients with HCC who undergo sorafenib treatment.     

Is the Cancer of the Liver Italian Program system an adequate weighting for survival of hepatocellular carcinoma? Evaluation of intrascore prognostic value among 36 subgroups

Background: The Cancer of the Liver Italian Program (CLIP) staging system for hepatocellular carcinoma (HCC) was subdivided into 36 subgroups. We aimed to validate the prognostic value of CLIP scoring. Methods: This study included 3868 HCC cases treated between 1986 and 2002. Survival and prognostic impact of all subgroups were analysed. Results: In primary CLIP, comparisons of each score showed a significant difference (P<0.001) and exhibited a linear trend (P<0.001). A CLIP score of 0 was used as control group. Portal vein thrombosis, Child–Pugh B, α‐fetoprotein (AFP) ≥400 ng/ml and multinodular with tumour extension ≤50% of the four subgroups with a CLIP score of 1 exhibited decreasing univariate hazard ratios and 95% confidence intervals, with values of 2.99 (2.05–4.37), 2.39 (2.00–2.86), 1.66 (1.40–1.96) and 1.39 (1.18–1.63) respectively. Homogeneity in the same score was evaluated by comparing subgroup survival curves. For scores 1–5, 83.3% (5/6), 57.1% (16/28), 24.4% (11/45), 3.6% (1/28) and 16.7% (1/6) pairs of survival curves significantly differed, respectively, with decreasing linear trend (P<0.001). Conclusion: Different prognostic weighting of four predictive factors caused intrascore heterogeneity. Lower CLIP scores were associated with increased differences in intrascore. In conclusion, the CLIP staging scoring system is a reasonable ordinal scale, but the clinician must be aware of the heterogeneity of mortality risk within a given score.     

Lymphadenectomy in the staging and treatment of intrahepatic cholangiocarcinoma: a population-based study using the National Cancer Institute SEER database

ObjectivesAlthough lymphatic spread is common in intrahepatic cholangiocarcinoma (ICC), lymphadenectomy is not widely performed as part of operative resection in this disease. The objectives of this study were to assess national trends for lymphadenectomy and its impact on survival in patients with ICC.MethodsThe National Cancer Institute's Surveillance, Epidemiology and End Results (SEER) registry was queried to identify patients with ICC (n= 4893) reported during 1988–2007. Kaplan–Maier and Cox proportional hazards regression were used to analyse survival.ResultsFive-year overall survival (OS) was 5.2%. Lymph node (LN) status was available for 48.9% (n= 2391) of patients. Histologic LN evaluation was performed in 13.5% (n= 658) of patients for a median of two (interquartile range: 1–3) LNs. During the study period, the frequency of histologic LN assessment (P= 0.78) did not change in liver resection patients. In the 733 resected patients, positive vs. negative LN status was associated with worse 5-year OS of 8.4% vs. 25.9%, respectively (hazard ratio = 1.8; P < 0.001).ConclusionsNodal status is an important prognostic factor for survival in patients diagnosed with ICC. In the USA, few patients undergo hepatic resection with lymphadenectomy; therefore, the clinical benefit of formal lymphadenectomy in ICC remains unknown.     

Natural history and prognostic factors of primary biliary cirrhosis in Taiwan: a follow‐up study up to 18 years

Purpose: The natural history of primary biliary cirrhosis (PBC) has been little studied in Asia. We conducted a Taiwanese cohort study on the natural history of PBC and analysed the prognostic factors. Methods: This study enrolled 96 consecutive PBC patients between 1985 and 2006 to evaluate the baseline characteristics and outcomes. Results: There were 74 females and 22 males. Eighty‐five were positive for antimitochondrial antibodies in sera, and 11 were negative. The clinical manifestations and prognosis were similar between these two groups. In a median follow‐up of 47.5±55.8 months, 27 patients died. Multivariate analysis indicated that the independent prognostic factors were serum albumin (P=0.021), creatinine (P=0.033) and ursodeoxycholic acid treatment (P=0.008). Besides, 42 patients developed adverse outcomes. Albumin (P<0.001), bilirubin (P=0.019) and prothrombin time (PT) (P=0.010) were significant factors. Moreover, a Mayo risk score <5, a Model for End‐Stage Liver Disease (MELD) score <6, a Child–Pugh stage A and early liver histology were associated with favourable outcomes. Conclusion: Serum albumin, bilirubin and PT were independent prognostic factors of adverse outcomes for Taiwanese PBC patients. Besides, the Mayo risk score, the MELD score, the Child–Pugh stage and liver histology were also validated to predict survival.     

Predictive factors for intrahepatic cholangiocarcinoma recurrence in the liver following surgery

Background We performed hepatectomy without lymph node (LN) dissection for intrahepatic cholangiocarcinoma (ICC) limited to the peripheral region of the liver, and hepatectomy with extrahepatic bile duct resection and regional LN dissection for any types of ICC extending to the hepatic hilum. Surgical outcomes were evaluated to elucidate the prognostic factors that influence patient survival with respect to intrahepatic recurrence. Methods Forty-one patients underwent resection of ICC with no macroscopic evidence of residual cancer. Results Significant risk factors for poorer survival included preoperative jaundice (P = 0.0115), serum CA19-9 levels >37 U/ml (P = 0.0089), tumor diameter >4.5 cm (P = 0.017), ICC extending to the hepatic hilum (P = 0.0065), mass-forming with periductal-infiltrating type (P = 0.003), poorly differentiated adenocarcinoma, portal vein involvement (P = 0.0785), LN metastasis at initial hepatectomy (P < 0.0001), and positive surgical margin (P = 0.023). Intrahepatic recurrence, which was the predominant manner of recurrence, was detected in 20 patients (74.1%). Patients with intrahepatic recurrence had a significantly high incidence of high serum CA19-9 levels (>37 U/ml; P = 0.0006), preoperative jaundice (P = 0.0262), ICC extended to the hepatic hilum (P = 0.0349), large tumors (>4.5 cm; P = 0.0351), portal vein involvement (P = 0.0423), and LN metastasis at initial hepatectomy (P = 0.009) compared with disease-free patients. The multiple logistic regression analysis revealed that preoperative CA19-9 elevation and obstructive jaundice influenced intrahepatic recurrence of ICC. Conclusions Although LN metastasis is a significant prognostic factor, the most obvious recurrence pattern after surgery was intrahepatic recurrence, which could be predicted preoperatively by a combination of elevated serum CA19-9 levels and manifestation of obstructive jaundice.     

Relative decrease in the role played by hepatitis B virus infection in the aetiology of hepatocellular carcinoma during a 20‐year period: a multicentre Italian study

Background: Chronic hepatitis B virus (HBV) infection is one of the most frequent aetiological factors associated with the development of hepatocellular carcinoma (HCC). Aim: This study evaluated the temporal trend in the aetiological role played by HBV infection alone in patients diagnosed with HCC during the last 20 years in Italy. Methods: Among the 2042 HCC patients included in the Italian Liver Cancer (ITA.LI.CA.) database, 346 had chronic HBV infection alone. We assessed the proportion of HCC patients with HBV infection in four quinquennia (1987–1991, 1992–1996, 1997–2001, 2002–2006) and evaluated their main clinical, virological and oncological characteristics across these periods. Results: Although the absolute number increased, the proportion of HBV‐related HCC relatively decreased over time from 26.7% (47/176 patients) in 1987–1991 to 14.7% (127/862 patients) in 2002–2006 (P=0.0005). Patients' demographical, clinical and virological characteristics were similar across the four quinquennia. A greater proportion of patients was diagnosed with non‐advanced HCC in more recent years (from 26% in 1987–1991 to 48% in 2002–2006, P=0.025), likely owing to a growing use of semiannual surveillance (from 63% in 1987–1991 to 80% in 2002–2006). Conclusions: We observed a significant, relative decrease in the role played by chronic HBV infection alone in the determinism of HCC during the last 20 years. In recent years, more patients are diagnosed with non‐advanced HCC probably owing to improvements in HCC detection.     

Risk factors for intrahepatic and extrahepatic cholangiocarcinoma: a case–control study in China

Background/Aims: The risk factors for cholangiocarcinoma are incompletely defined in China, especially for intrahepatic cholangiocarcinoma (ICC). We evaluated the risk factors for both ICC and extrahepatic cholangiocarcinoma (ECC). Methods: A case–control study in which cases were cholangiocarcinoma patients referred to Peking Union Medical College Hospital (PUMCH) between 1998 and 2008 and controls were healthy individuals. Controls were randomly selected from an existing database of healthy individuals at the Health Screening Center of PUMCH. Data on liver disease, family history, diabetes, smoking and drinking were collected by a retrospective review of the patients' records and health examination reports or by interview. Results: A total of 190 patients (61 ICC; 129 ECC) and 380 age‐ and sex‐matched controls were enrolled. HBsAg (P<0.001) and anti‐HBc without HBsAg (P=0.001) were significantly related to ICC. The adjusted odds ratios (OR) and 95% confidence intervals (CI) were 18.1 (95% CI: 7.5–44.0) and 3.6 (95% CI: 1.7–7.6) respectively. Diabetes mellitus (P=0.007), cholecystolithiasis (P=0.004) and previous cholecystectomy (P<0.001) were significantly associated with ECC. The prevalence of cirrhosis was higher in ICC than that in ECC (P<0.001). Furthermore, on excluding the ICC patients with cirrhosis, ICC patients showed significant independent associations with HBsAg (OR: 7.3; 95% CI: 3.1–17.2) and anti‐HBc without HBsAg (OR: 2.4; 95% CI: 1.1–5.2). Conclusion: Cirrhosis and chronic hepatitis B virus infection are risk factors for ICC, while cholecystolithiasis, diabetes and previous cholecystectomy are risk factors for ECC.