The combined use of serum neurotensin and IL-8 as screening markers for colorectal cancer.

This pilot study aimed to determine the feasibility of serum neurotensin/IL-8 values being used as a screening tool for colorectal cancer. Fifty-six patients and 15 healthy controls were assigned to seven groups according to their disease entity based on theater records and histology report. Blood samples for neurotensin and IL-8 were measured using an enzyme-linked immunosorbent assay. There were no differences in the clinical and biochemical parameters of patients and controls. Group (p=0.003) and age (p=0.059, marginally significant) were independent predictors of neurotensin plasma values. Neurotensin (p=0.004) and IL-8 (p=0.029) differed between healthy and colorectal cancer patients. Neurotensin values differentiate the control group from all remaining groups. The value of plasma neurotensin ≤ 54.47 pg/ml at enrollment selected by receiver operating characteristic (ROC) curves demonstrated a sensitivity of 77 %, specificity of 90 %, and an estimate of area under ROC curve (accuracy) of 85 % in predicting colorectal cancer. At enrollment, the value of plasma IL-8 ≥ 8.83 pg/ml had a sensitivity of 85 %, specificity 80 %, and an estimate of area under ROC curve (accuracy) of 81 % in predicting colorectal cancer. IL-8 should be used complementary to neurotensin due to its lower specificity. None of the colorectal cancer patients displayed a combination of high neurotensin and low IL-8 values (beyond cutoffs). It seems that a blood neurotensin/IL-8 system may be used as a screening tool for colorectal cancer, but much has to be done before it is validated in larger-scale prospective studies.

Laparoscopic totally extraperitoneal versus open preperitoneal mesh repair for inguinal hernia recurrence: a decision analysis based on net health benefits.

BACKGROUND: The aim of this study is to evaluate the most cost-effective treatment strategy using preperitoneal mesh for patients with recurrent inguinal hernia. Currently, the issue of cost-effectiveness is entirely unresolved. METHODS: A decision analysis was carried out based on the results of a systematic literature review of articles concerning recurrent inguinal hernia repair that were published between 1979 and 2011. A virtual cohort was programmed to undergo three different treatment procedures: (1) laparoscopic totally extraperitoneal hernia repair (TEP), (2) open preperitoneal mesh repair according to Stoppa, and (3) open preperitoneal mesh repair according to Nyhus. We carried out a base-case analysis and varied all variables over a broad range of reasonable hypotheses in multiple one-way and two-way sensitivity analyses. RESULTS: The average cost-effectiveness ratio of Nyhus, Stoppa, and TEP per quality-adjusted life year was US $ ($)1,942, $1,948, and $2,011, respectively. In terms of the incremental cost-effectiveness ratio (ICER), Stoppa was dominated. The choice between TEP or Nyhus procedure depends on the combination of a specific center's rates of recurrence and morbidity as disclosed by three-way sensitivity analysis. CONCLUSIONS: Nyhus and TEP repairs are possible optimal choices depending primarily on the institution's rates of recurrence and morbidity. Based on our net benefit-related decision analysis, a hypothetical "fixed budget trade-off" suggests potential annual incremental health system cost savings of $200,000 attained by shifting care for 1,000 patients from TEP to Nyhus repair (depending on clinical end-points, which is a decisive factor).

Prognostic scoring system predictive of survival after surgical resection of esophageal carcinoma.

BACKGROUND: The aim of our study was to develop a prognostic index score for patients undergoing surgical resection for esophageal cancer that accurately determines survival with specific clinicopathological characteristics. METHODS: Clinical, histological, and demographical variables of 475 patients were entered in an univariate and multivariate regression model, followed by individual calculation of the Prognostic Indicator Score and model validation via simulation. RESULTS: Significant variables included in the scoring system were number of positive lymph nodes, pT, pL, R, obesity, and American Society of Anesthesiologist classification. Survival probability and its associated hazard function was significantly different between the scores, with an increase of hazard ratio ranging from 2.56 (score 2) to 20 (score 6 or higher). Comparing histological cancer entities revealed statistical significance only between stage IIA versus IIB in squamous cell and stage IIIA versus IIIB in adenocarcinoma. CONCLUSIONS: According to our methodology, an individualized follow-up by each possible score might allow interdisciplinary selection of patients for treatments based on expected survival. This may represent a breakthrough in patient selection for currently available treatments and clinical studies.

Survival after chemotherapy and/or radiotherapy versus self-expanding metal stent insertion in the setting of inoperable esophageal cancer: a case-control study.

BACKGROUND: Our aim was to compare survival of the various treatment modality groups of chemotherapy and/or radiotherapy in relation to SEMS (self-expanding metal stents) in a retrospective case-control study. We have made the hypothesis that the administration of combined chemoradiotherapy improves survival in inoperable esophageal cancer patients. METHODS: All patients were confirmed histologically as having surgically non- resectable esophageal carcinoma. Included were patients with squamous cell carcinoma, undifferentiated carcinoma as well as Siewert type I--but not type II - esophagogastric junctional adenocarcinoma. The decision to proceed with palliative treatments was taken within the context of a multidisciplinary team meeting and full expert review based on patient's wish, co-morbid disease, clinical metastases, distant metastases, M1 nodal metastases, T4-tumor airway, aorta, main stem bronchi, cardiac invasion, and peritoneal disease. Patients not fit enough to tolerate a radical course of definitive chemo- and/or radiation therapy were referred for self-expanding metal stent insertion. Our approach to deal with potential confounders was to match subjects according to their clinical characteristics (contraindications for surgery) and tumor stage according to diagnostic work-up in four groups: SEMS group (A), Chemotherapy group (B), Radiotherapy group (C), and Chemoradiotherapy group (D). RESULTS: Esophagectomy was contraindicated in 155 (35.5%) out of 437 patients presenting with esophageal cancer to the Department of General and Abdominal Surgery of the University Hospital of Mainz, Germany, between November 1997 and November 2007. There were 133 males and 22 females with a median age of 64.3 (43-88) years. Out of 155 patients, 123 were assigned to four groups: SEMS group (A) n = 26, Chemotherapy group (B) n = 12, Radiotherapy group (C) n = 23 and Chemoradiotherapy group (D) n = 62. Mean patient survival for the 4 groups was as follows: Group A: 6.92 ± 8.4 months; Group B: 7.75 ± 6.6 months; Group C: 8.56 ± 9.5 months, and Group D: 13.53 ± 14.7 months. Significant differences in overall survival were associated with tumor histology (P = 0.027), tumor localization (P = 0.019), and type of therapy (P = 0.005), respectively, in univariate analysis. Treatment modality (P = 0.043) was the only independent predictor of survival in multivariate analysis. The difference in overall survival between Group A and Group D was highly significant (P < 0.01) and in favor of Group D. As concerns Group D versus Group B and Group D versus Group C there was a trend towards a difference in overall survival in favor of Group D (P = 0.069 and P = 0.059, respectively). CONCLUSIONS: The prognosis of inoperable esophageal cancer seems to be highly dependent on the suitability of the induction of patient-specific therapeutic measures and is significantly better, when chemoradiotherapy is applied.

The effect of warm liver ischaemia & reperfusion injury on circulating plasma lipid levels & lipolytic enzyme activity in rat & the impact of ischaemic preconditioning.

BACKGROUND & OBJECTIVES: Ischaemia/reperfusion (I/R) associated with major liver surgery compromises liver function. Ischaemic preconditioning (IPC) may be effective in minimizing hepatic I/R injury. This study aimed to investigate the impact of liver ischaemic manipulations on lipid metabolism in rat during the process of liver recovery after liver surgery. METHODS: Sixty three male Wistar rats were assigned to three groups: the sham group, the I/R group which underwent warm ischaemia and reperfusion (I/R), and the IPC group. The animals were subdivided in 3 groups [1 st , 3 rd and 7 th postoperative day (PO)]. Hepatic lipase (HL) and total lipase (TL) activity and the levels of aspartate and alanine transaminases (AST, ALT), triglycerides, HDL and cholesterol were measured in plasma. RESULTS: There was no significant difference in the activity of HL and TL between the groups. Significant higher levels of HDL (P<0.0001) were observed in the IPC group when compared to the other groups on the 3 rd PO day. Triglycerides (P<0.0001) and HDL (P=0.003) in the IPC group were higher than the sham group on the 7 th PO day while HDL was also higher in the I/R group. Significantly higher cholesterol levels were found in the I/R and IPC groups on the 7 th PO day, which were not observed in the sham group. There was a similar curve for triglycerides in the sham and IPC groups while there were significantly higher levels of triglycerides on day 7 for the I/R group. The levels of HDL in the IPC group were higher on the 3 rd and 7 th PO day, compared to day 1. INTERPRETATION & CONCLUSION: Warm ischaemia and I/R injury do not seem to affect lipolytic enzyme activity after the 1 st PO day despite the effects on plasma lipids. IPC seems to prevent accumulation of triglycerides and cholesterol in plasma.

Portal and Hepatic Venous Territorial Mapping in Healthy Human Livers: Virtual Three-Dimensional Computed Tomography Size-Shape-Topography Study.

OBJECTIVES: This study aimed to assess portal and hepatic venous volumes as related to the planning of complex liver resections and segmental liver transplant. MATERIALS AND METHODS: We analyzed 3-dimensional computed tomography of portal and hepatic vein territorial maps of 140 potential living related liver donors. Portal and hepatic vein maps were simulated both separately and in overlap (cross-mapping) to calculate inflow and outflow volumes. RESULTS: In total liver volume, the right hemiliver was always dominant (mean 64.7 ± 4.8%) and the right medial sector (mean 36.4 ± 6.8%) and segment 8 (mean 19.1 ± 4.3%) accounted for the largest volumes, whereas the left medial sector(mean 13.5 ± 3.1%) and segment 4A (mean 5.8 ± 1.8%) accounted for the smallest volumes (with exclusion of caudate lobe). The right hepatic vein was dominant for both right hemiliver and right lateral sector and had the largest drainage volume in total liver volume (mean 40.0 ± 11.2%). The left hepatic vein was dominant for both left hemiliver and left lateral sector but had the smallest drainage volume fortotal liver volume (mean 21.3 ± 5.0%). The middle hepatic vein drained 50.2 ± 12.5% of the right medial sector and 75.8 ± 15.4% of the left medial sector. In 67 cases, an accessory vein (inferior hepatic vein) drained 16.5 ± 13.2% ofthe right hemiliver, 31.4 ± 25.1% ofthe right lateral sector, 26.6 ± 23.2% of segment 7, and 37.4 ± 31.3% of segment 6. CONCLUSIONS: The portal and hepatic vein territorial anatomy was characterized by extensive individual variability. An extremely smallremnant volume (<25% of total liver volume) precluded a minority of virtual extended left and a majority of extended right hepatectomies. Left trisectionectomy was associated with risky drainage from the middle hepatic vein, extensive segment 6 remnant congestion volume in 8% of cases, and right lateral sector-favorable inferior hepatic vein large drainage pattern in 13% of livers.

"Anatomical" versus "territorial" belonging of the middle hepatic vein: virtual imaging and clinical repercussions.

BACKGROUND: Venous drainage patterns are of vital importance in live donor liver transplantation. The purpose of this study was to delineate "anatomical-topographical" and "territorial-physiologic" patterns of the middle hepatic vein (MHV) in a 3-D liver model as determined by the Pringle line and its drainage volume of the right and left hemilivers. METHODS: One hundred thirty-seven consecutive live donor candidates were evaluated by 3-D CT reconstructions and virtual hepatectomies. Based on right (R) and left (L), anatomical (A) and territorial (T) belonging patterns of the MHV, each individual was assigned to one of four possible types: type I:A(R)-T(R); type II:A(L)-T(L); type III:A(R)-T(L); type IV:A(L)-T(R). Couinaud's anatomical MHV variants A-C were subsequently included in our combined anatomical/territorial MHV belonging classification. RESULTS: The MHV showed a significant predominance of right "anatomical" (59.1%) and left "territorial" belonging patterns (65.7%). The paradoxical combinations A(R)-T(L) (type III) and A(L)-T(R) (type IV) were encountered in 36.5% and 11.7% of cases, respectively. The constellations Couinaud's A-belonging type IV and Couinaud's C-belonging type IV were predictive of right hemiliver venous congestion. CONCLUSIONS: (1) Almost half of all livers in our series had paradoxical "anatomical"/"territorial" MHV belonging patterns that placed them at risk for right and left hepatectomies. (2) The proposed combined "anatomical"/"territorial" MHV belonging types (I-IV) provide useful preoperative information. (3) Combined types III and IV as well as Couinaud's A-IV, and Couinaud's C-IV should be considered particularly risky for venous congestion in right hemiliver grafts and in extended left hepatectomies.

VEGF-D correlates with metastatic disease in gastric cancer patients undergoing surgery.

BACKGROUND: The present study was designed to evaluate the impact of the tyrosine kinase ligands VEGF-A/C/D, PDGF-A/B on tumor dissemination and survival in gastric cancer. This is the first study analyzing all these parameters in a homogeneous patient population undergoing surgery. METHODS: The expression pattern of VEGF-A/C/D and PDGF-A/B was analyzed by reverse transcriptase polymerase chain reaction (RT-PCR) in 69 samples of human gastric adenocarcinoma and correlated with tumor stage and survival. RESULTS: Expression of the ligand VEGF-D significantly correlated with distant metastatic disease (P=0.00001) but not with patient survival. However, VEGF-A inversely correlated with M1 and grading, PDGF-A inversely correlated with pT and pN category. In contrast, VEGF-C and PDGF-B did not have an impact on clinicopathological parameters. CONCLUSIONS: The ligand VEGF-D, rather than the other ligands or tyrosine kinase receptors analyzed, is associated with progressive disease in gastric cancer patients undergoing surgery. The VEGF-D ligand might be a helpful marker indicating disseminated disease, and targeting VEGF-D may be a potential therapeutic strategy, although limitations imposed by the selected sample population have to be considered critically.

Incidental findings in focused assessment with sonography for trauma in hemodynamically stable blunt trauma patients: speaking about cost to benefit.

BACKGROUND: The purpose of this study was to identify which age-related groups of hemodynamically stable blunt trauma patients will present a positive cost-to-benefit ratio, in regard to the screening of incidental findings on Focused Assessment with Sonography for Trauma (FAST). METHODS: We conducted a prospective study using retrospective data taken from the trauma registry of 6,041 consecutive hemodynamically stable blunt trauma patients who underwent FAST at our Level I urban trauma hospital during the year 2009. A receiver operating characteristic curve was used to determine whether age level is useful in detecting organ-/system-specific incidental findings in trauma patients undergoing FAST and to establish the required diagnostic cutoff value of this selected test. A cost-benefit analysis was then performed for the age-specific cutoff values of each organ/system evaluated by FAST. RESULTS: We found 522 incidental findings in 468 patients (7.8%). Further diagnostic workup was instructed in 35% (168 of 468) of patients with incidental findings. The cost-benefit analysis for the age-specific cutoff values found in the receiver operating characteristic curve analysis showed that the project of screening for incidental findings on FAST was viable only when the ultrasound operator additionally searches the liver/biliary tree (≥43 years) and the kidneys (≥56 years). CONCLUSIONS: A systematic examination of the liver and biliary tree and both kidneys of specific age groups during FAST screening of hemodynamically stable blunt trauma patients may disclose a potentially unknown pathology with a positive cost-to-benefit ratio.

Comparison of skin-sparing mastectomy versus non-skin-sparing mastectomy for breast cancer: a meta-analysis of observational studies.

OBJECTIVES: To evaluate differences in outcomes of breast cancer patients undergoing either conventional mastectomy without reconstruction (NSSM) or skin-sparing mastectomy (SSM) with immediate reconstruction. DATA SOURCES: All comparative studies published between 1997 and 2009 were used to evaluate local recurrence and distant relapse in the 2 study groups. REVIEW METHODS: Meta-analytical models were used to evaluate the study outcomes. Sensitivity analysis, was carried out to evaluate the robustness of the pooled estimates and assess the between-study heterogeneity. RESULTS: Nine studies, comprising of 3739 patients (1104 SSM and 2635 NSSM) were included in the analysis. There were no significant differences in the disease stage or the proportion of invasive cancers between groups (73.9% vs. 83.8%, P = 0.65). There was no significant difference in local recurrence between the SSM versus NSSM groups (7 studies, 3436 patients, 6.2% vs. 4.0%, odds ratio = 1.25, 95% CI: 0.81-1.94) and there was no significant heterogeneity between the studies. The SSM group had a lower proportion of distant relapses compared with the NSSM group (5 studies, 2122 patients, 10.0% vs. 12.7%, odds ratio = 0.67, 95% CI: 0.48-0.94) but this should be interpreted with caution since the grade of the tumors was not adequately reported in the studies considered. CONCLUSIONS: Our results suggest that in breast cancer patients, SSM was not significantly different from NSSM, in terms of rates of local recurrence. As no randomized control trial has addressed this question to date, the present meta-analysis reports the best evidence on the subject.

Multicentric evaluation of a clinical and prognostic scoring system predictive of survival after resection of intrahepatic cholangiocarcinomas.

OBJECTIVE: To develop a clinical and prognostic scoring system predictive of survival after resection of intrahepatic cholangiocarcinomas (ICC). PATIENTS: Two hundred and one consecutive ICC patients (83 from Essen, Germany, 54 from New York, USA and 64 from Chiba, Japan). The scoring systems were developed utilizing the data set from Essen University and then applied to the data sets from Mount Sinai Medical Center and Chiba University for validation. Eighteen potential prognostic factors were evaluated. Statistical analysis included multivariable regression analyses with the Cox proportional hazard model, power analysis, internal validation with structural equation modelling bootstrapping and external validation. The prognostic scoring model was based mainly in pathological and demographical variables, whereas the clinical scoring model was based mainly in radiological and demographical variables. RESULTS: Gender (P=0.0086), UICC stage (P=0.0140) and R-class (P=0.0016) were predictive of survival for the prognostic scoring model, while gender (P=0.0023), CA 19-9 levels (P=0.0153) and macrovascular invasion (P=0.0067) were predictive of survival for the clinical scoring model. Prognostic points were assigned as follows: female:male=1:2 points, UICC (I-II):UICC (III-IV)=1:2 points and R0:R1=1:2 points. Clinical points were allocated as follows: female:male=1:2 points, CA 19-9 (<100 U/ml):CA 19-9 (> or =100 U/ml)=1:2 points and no macrovascular invasion:macrovascular invasion=1:2 points. Prognostic groups with 3-4, 5 and 6 points (P=0.000001) and clinical groups with 3-4 and 5-6 points (P=0.0103) achieved statistically significant difference. CONCLUSIONS: We propose a clinical and prognostic scoring system predictive of long-term survival after surgical resections for ICC.

Low expression of chemokine receptor CCR5 in human colorectal cancer correlates with lymphatic dissemination and reduced CD8+ T-cell infiltration.

BACKGROUND: Chemokines and their receptors have been proposed to distinctly contribute to tumor growth, dissemination, and local immune escape. The aim of this study was to evaluate the relevance of the chemokine receptor CCR5 expression for the progression of human colorectal cancer. METHODS: CCR5 expression was assessed by RT-PCR analysis in 103 colorectal cancer patients. Intensity of CCR5 expression was correlated with both tumor and patient characteristics. Infiltration of tumor margins with CD8(+) T cells in the context of CCR5 expression was analyzed by immunohistochemistry in additional 18 colorectal cancer specimens. RESULTS: Human colorectal cancer revealed variable intensities of CCR5 expression ranging from absent (48/103: 47%), weak (30/103: 29%), intermediate (13/103: 13%), to strong (12/103: 12%). Absent or weak CCR5 expression was significantly associated with advanced UICC stages (P=0.02) and lymphatic metastasis (P=0.05). In addition, CCR5 expression positively correlated with CD8(+) T-cell infiltration in tumor margins (P=0.001). CONCLUSION: In summary, intermediate and strong CCR5 expression was significantly associated with nonmetastatic colorectal cancer and increased CD8(+) T-cell infiltration.

Minimally invasive versus open esophagectomy: meta-analysis of outcomes.

BACKGROUND: A meta-analysis of the current literature was performed to compare the perioperative outcome measures and oncological impact between minimally invasive and open esophagectomy. METHODS: Using the electronic databases Medline, Embase, Pubmed and the Cochrane Library, we performed a meta-analysis pooling the effects of outcomes of 1,008 patients enrolled into eight comparative studies, using classic and modern meta-analytic methods. RESULTS: Two comparisons were considered for this systematic review: (I) open thoracotomy vs. VATS/laparoscopy esophagectomy and (II) open thoracotomy vs. VATS esophagectomy. In comparison I: both procedures report equally comparable outcomes (removed lymph nodes, 30-day mortality, 3-year survival) with the exception of overall morbidity (P = 0.038; in favor of the MIE arm) and anastomotic stricture (P < 0.001; in favor of the open thoracotomy arm). In comparison II: No differences were noted between treatment arms concerning postoperative outcomes and survival. CONCLUSIONS: In summary, both arms were comparable with regard to perioperative results and prognosis. Further prospective comparative or randomized-controlled trials focusing on the oncological impact of MIE are needed.

The use of self-expanding stents in esophageal and gastroesophageal junction cancer palliation: a meta-analysis and meta-regression analysis of outcomes.

BACKGROUND: The objective of this study was to examine the impact of self-expanding stents versus locoregional treatment modalities in the setting of esophageal cancer palliation. METHODS: The present meta-analysis pooled the effects of outcomes of 1,027 patients enrolled in 16 randomized controlled trials. RESULTS: The meta-analysis revealed an advantage to the use of stents compared to locoregional modality treatments with respect to the number of patients requiring reinterventions, although the latter treatment arm had a higher 1-year survival. No difference was observed between the use of the antireflux stents and conventional stents in relieving reflux. Previous chemoradiotherapy had no impact on complications, procedural deaths, and overall patient survival. Differences in outcomes among stents were minimal. CONCLUSIONS: Conventional self-expanding stents and anti-reflux stents are equally effective. Although the risk difference for 1-year survival favoured locoregional palliative treatment modalities, the latter were associated with a higher number of patients requiring reintervention.

Surgical treatment of Klatskin tumor: liver resection versus transplantation.

BACKGROUND: Our objective was to evaluate liver transplantation as a treatment option for Klatskin tumor. Results for transplanted patients suffering from hilar cholangiocarcinoma were therefore compared to patients after hemihepatectomy. METHODOLOGY: In a retrospective case-control study, seven patients transplanted for hilar cholangiocarcinoma were matched in terms of UICC stage with seven patients who underwent resection of the hilar bifurcation combined with a hemihepatectomy. RESULTS: Median survival was 22 months (range 1-55 months) for patients after liver resection and 64 months (range 1-138 months) for patients after liver transplantation. One and three year overall survival was 71% and 43% after liver resection versus 71% and 57% after liver transplantation. One patient from each group died within one month after surgery. Fatal cerebral bleeding and post-resection liver failure leading to multi-organ failure and sepsis were the causes of early mortality. Three patients are currently alive: one with 64 months after transplantation and two patients with 42 and 55 months after liver resection. CONCLUSIONS: Based on our findings and recently published promising results using liver transplantation for Klatskin tumor, it seems worthwhile to reconsider its potential use in the light of multimodal tumor treatment.

Corticosteroid-free immunosuppression in liver transplantation: a meta-analysis and meta-regression of outcomes.

To examine the impact of steroid withdrawal from the immunosuppression protocols in liver transplantation. The electronic databases Medline, Embase, Pubmed and the Cochrane Library were searched. Meta-analysis pooled the effects of outcomes of a total of 2590 patients enrolled into 21 randomized controlled trials (RCTs), using classic and modern meta-analytic methods. Meta-analysis of RCTs addressing patients transplanted for any indication showed no differences between corticosteroid-free immunosuppression and steroid-based protocols in most of the analyzed outcomes. More importantly, steroid-free cohorts appeared to benefit in terms of de novo diabetes mellitus development [R.R = 1.86 (1.43, 2.41)], Cytomegalovirus (CMV) infection [R.R = 1.47 (0.99, 2.17)], cholesterol levels [WMD = 19.71 (13.7, 25.7)], the number of patients that received the allocated treatment [O.R = 1.55 (1.17, 2.05)], severe acute rejection [R.R = 1.71 (1.14, 2.54)] and overall acute rejection [R.R = 1.31 (1.09, 1.58)] (when steroids were replaced in the steroid-free arm). Taking RCTs into account independently when steroids were not replaced, overall acute rejection was favoring the steroid-based arm [R.R = 0.75 (0.58, 0.98)]. Studies addressing exclusively transplanted HCV patients demonstrated a significant advantage of steroid-free protocols considering HCV recurrence [R.R = 1.15 (1.01, 1.13)], acute graft hepatitis [O.R = 3.15 (1.18, 8.40)], and treatment failure [O.R = 1.87 (1.33, 2.63)]. No unfavorable effects were observed after steroid withdrawal during short-term follow-up. On the contrary, significant advantages were documented.

Prognostic impact of intrahepatic lymphatic and microvascular involvement in cases of colorectal liver metastases.

OBJECTIVE: The purpose of this study was to evaluate the effect of intrahepatic microvascular and lymphatic infiltration on survival in cases of colorectal liver metastases. MATERIALS AND METHODS: Prospectively collected data of 331 patients were analyzed for microvascular invasion (V), lymphatic infiltration (L), and resection margins (R) with respect to overall and disease-free survival. RESULTS: One-, 3-, and 5-year overall survival rates for R0 resected patients were 89%, 64%, and 39%, respectively. The corresponding survival rates for R1 resected patients were 83%, 42%, and 24% (p < 0.001). The sole presence of microvascular invasion (V1) or lymphatic infiltration (L1) was not associated with a diminished overall survival (p > 0.05). However, patients with a combination of L1V1 had a significantly worse overall survival of 68%, 20%, and 0% when compared to L0V0 patients. This difference was not influenced by the status of the resection margin. No other parameter investigated was found to be of predictive value. CONCLUSIONS: The presence of combined lymphatic and vascular invasion (L1V1) constitutes a predictor of poor overall and disease-free survival. This subgroup of patients might benefit from adjuvant strategies such as chemotherapeutic treatment.

Liberal policy in living donor liver transplantation for hepatocellular carcinoma: lessons learned.

BACKGROUND: Living donor liver transplantation (LDLT) in cases of hepatocellular carcinoma (HCC) that do not fulfil accepted tumor criteria continues to be a matter of controversy. The aim of this study was to evaluate survival and prognostic factors associated with a liberal exclusionary policy. MATERIAL AND METHODS: This is an analysis of data collected prospectively on 57 HCC patients who underwent LDLT at our institution between April 1998 and January 2007. RESULTS: Overall 3-year survival was 62%; this increased to 71% when 45-day mortality was excluded from the analysis. Age proved to be a predictor of survival irrespective of the 45-day mortality. In contrast, the Model for End stage Liver Disease (MELD) score predicted survival only when 45-day mortality was included in the analysis, while alpha fetoprotein (AFP) level predicted survival only when it was excluded. Significant cut-off values were patient age of over 60 years, MELD score above 22, and AFP level greater than 400 ng/ml. A scoring system was developed. Survival rate at 3 years--including 45-day mortality--was 72% for score =2 and 41% for score >2 (P = 0.0146). When 45-day mortality was excluded, the survival rate at 3 years was 90% for score =2 and 32% for score >2 (P = 0.00002). CONCLUSIONS: Our results could further enhance current guidelines on age, MELD score, and AFP level for patients with HCC being evaluated to undergo LDLT.

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.

Liver transplantation, liver resection, and transarterial chemoembolization for hepatocellular carcinoma in cirrhosis: which is the best oncological approach?

The aim of the study was to evaluate our institutional experience with monotherapies for hepatocellular carcinoma (HCC) in the setting of cirrhosis. A retrospective cohort study was carried out at the tertiary care academic referral center and involved 185 consecutive HCC patients with cirrhosis and no previous treatment who underwent resection (n = 61), transarterial chemoembolization (TACE) (n = 64), or liver transplantation (LT) (n = 60). Long-term survival and survival according to the Milan criteria were the main outcomes measured. Median survival after resection, TACE, and LT was 11, 14, and 23 months, respectively. Five-year cumulative survival after resection, TACE, and LT was 23, 10, and 59%, respectively (P = 0.001). Five-year cumulative disease-free survival after resection and LT was 15% and 77%, respectively (P = 0.002). The presence of complications in the resection group (P = 0.004), MELD score (P = 0.0003), and maximum tumor diameter (P = 0.05) in the TACE group, and tumor grade (P = 0.01) and complications (P = 0.004) in the LT group were found to be independent predictors of survival. Five-year survival for patients within the Milan criteria after resection, TACE, and LT was 26, 37, and 66%, respectively. Five-year survival for patients outside the Milan criteria for patients undergoing LT was 53%. The results suggest that LT represents the best oncological treatment option for patients with HCC in the setting of cirrhosis, even for those beyond the Milan criteria. Considering the scarcity of available organs, liver resection remains the best alternative option. TACE remains a potential therapy in patients within the Milan criteria, where it may be more beneficial than resection.