Search

Background: Failure of portal vein ligation (PVL) to induce hypertrophy is not uncommon. The aim of the study was to evaluate the impact of intraportal alcohol injection prior to ligation on liver regeneration., Method: Forty-two patients with colorectal liver metastases who underwent PVL between 01/2004 and 06/2014 were analyzed. Beginning in 09/2011, alcohol was injected prior to PVL. Patients treated with PVL alone (Alc- group) were compared with those treated with alcohol injection plus PVL (Alc+ group). Liver regeneration was assessed by volumetric increase (VI)., Results: Alc+ (23 patients) and Alc- (19 patients) groups were similar in terms of age, sex and pre-PVL FLRV. Alc- group had a higher risk of recanalization (12 vs. 1, p < 0.001) and cavernous transformation (7 vs. 2, p = 0.055) of the occluded portal vein. Post-PVL FLRV (43.3 ± 14.3% vs. 34.6 ± 6.4%, p = 0.013) and VI (0.44 ± 0.24 vs. 0.28 ± 0.20, p = 0.029) were higher in Alc+ group. On multivariate analysis male sex (B = -0.149) and alcohol injection (B = 0.143) significantly predicted VI., Conclusions: Alcohol injection prior to PVL may increase the regeneration of the FLRV by reducing the recanalization of the occluded portal vein., (Copyright © 2018 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Background: Percutaneous transhepatic biliary drainage (PTBD) has a crucial role in treatment of proximal biliary cancer (PBC). We assessed the incidence, risk factors, and impact of acute pancreatitis (AP) post-PTBD., Methods: Forty patients with PBC scheduled for PTBD from January 2005 to December 2015 were enrolled. Exclusion criteria were missing clinical data, PTBD performed in other institutions, and palliative PTBD., Result: The 40 patients comprised 8 (20%) with gallbladder cancer, 6 (15%) with intrahepatic cholangiocarcinoma, and 26 (65%) with perihilar cholangiocarcinoma. A median of 1 PTBD procedure was performed per patient; 16 (40%) patients underwent PTBD more than once. PTBD was left-sided in 14 (35.0%) patients, right-sided in 21 (52.5%), and bilobar in 5(12.5%). Seventeen (42.5%) patients had one or more drainage-related complications. Five (12.5%) patients developed AP. A significantly higher percentage of patients with than without AP developed sepsis (60.0 vs. 11.4%, respectively) and did not undergo the planned liver resection [2 (40.0%) vs. 0 (0.0%), respectively]. Significantly more patients with than without AP underwent left-sided PTBD [10 (28.6%) vs. 4 (80.0%), respectively]., Conclusion: PTBD is frequently complicated by AP. AP plays a key role in the development of sepsis. Nearly half of patients with AP lose the opportunity for surgical treatment.

The influence of housing on cognition and emotional regulation in mice presents a problem for the study of genetic and environmental risk factors for neuropsychiatric disorders: standard laboratory housing may result in low levels of cognitive function or altered levels of anxiety that leave little room for assessment of deleterious effects of experimental manipulations. The use of enriched environment (EE) may allow for the measurement of a wider range of performance in cognitive domains. Cognitive and behavioral effects of EE in male mice have not been widely reproduced, perhaps due to variability in the application of enrichment protocols, and the effects of EE in female mice have not been widely studied. We have developed an EE protocol using common laboratory equipment that, without a running wheel for exercise, results in significant cognitive and behavioral effects relative to standard laboratory housing conditions. We compared male and female wild-type C57BL/6J mice reared from weaning age in an EE to those reared in a standard environment (SE), using common measures of anxiety-like behavior, sensory gating, sociability, and spatial learning and memory. Sex was a significant factor in relevant elevated plus maze (EPM) measures, and bordered on significance in a social interaction (SI) assay. Effects of EE on anxiety-like behavior and sociability were indicative of a general increase in exploratory activity. In male and female mice, EE resulted in reduced prepulse inhibition (PPI) of the acoustic startle response, and enhanced spatial learning and use of spatially precise strategies in a Morris water maze task., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: The aim of the study was to assess the capacity of indocyanine green retention test at 15 min (ICGR15) to predict chemotherapeutic-associated liver injuries (CALI)., Methods: Patients undergoing liver resection for CLM that received preoperative oxaliplatin and/or irintecan-based chemotherapy within 3 months before surgery and scheduled first hepatectomy were considered., Results: 166 out of 983 patients treated between 01/2001 and 04/2014 fulfilled the inclusion criteria. The median number of cycles of preoperative chemotherapy was 6.0 ± 4.87. Chemotherapy was mainly based on oxaliplatin in 123 (74.1%). Bevacizumab was associated in 51(31%) patients. A total of 102 (61.4%) patients had at least 1 CALI. Grade 2-3 steatosis occurred in 56 (33.7%) patients and steatohepatitis in19(11.5%). Sinusoidal obstructive syndrome (SOS) was presented in 93 (56%) patients. 23(13.8%) patients had nodular regeneration hyperplasia. At multivariate analysis the only predictive factor of ICGR≥10% was age≥65 years (p = 0.001). A median split (ICGR15 = 8%) was used to categorized ICGR15 value. Multivariate analysis showed that age≥ 65 [OR 2.530 (CI95% 1.28-4.97) p < 0.001], male sex [OR 2.614 (CI95% 1.31-5.20) p < 0.001], SOS [OR 1.954 (CI95% 1.00-3.81) p = 0.050] and administration of Bevacizumab [OR 2.201 (CI95% 1.07-4.50) p = 0.031] were predictive factors for ICGR≥8%., Conclusions: ICGR15 test can predict the diagnosis of SOS. High ICGR15 value is more common in elderly male patients and after bevacizumab administration., (Copyright © 2016 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.)

Background: Intratumoral bleeding and/or intraperitoneal rupture occurs in up to 20% of patients with hepatocellular adenoma (HCA). Hepatectomy in the presence of haemorrhagic HCA has been associated with increased morbidity and mortality rates. This study evaluates the outcomes of hepatectomy for haemorrhagic HCA at a single institution., Methods: Between January 1997 and December 2012, 52 consecutive patients underwent liver resection for HCA. Among them, 14 patients were resected for haemorrhagic (H)-HCAs (including 9 cases of intratumoural bleeding and 5 cases of intraperitoneal bleeding) and 38 for non-haemorrhagic (NH)-HCAs., Results: The preoperative characteristics were similar between the two groups except for younger age (p = .001) and shorter duration of hormonal use (p = .001) in (H)-HCAs. There were no mortalities. Intraoperative blood loss, transfusion rate, and postoperative morbidity were comparable between the two groups of patients (p = ns). The length of hospital stay was significantly longer in (H)-HCAs (p = .03). In all the resected H-HCAs, pathology showed central haemorrhagic changes with tumoral cells at the periphery of the lesions., Conclusions: Liver resection for H- and NH-HCAs can be achieved with no mortality and comparable short-term outcomes., (Copyright © 2016 IJS Publishing Group Limited. Published by Elsevier Ltd. All rights reserved.)

Background: Despite extensive preoperative evaluation, a significant proportion of patients with biliary cancer (BC) proves to be unresectable at laparotomy. Diagnostic laparoscopy (DL) has been suggested to avoid unnecessary laparotomy. Aim of the study was to evaluate the additional benefit of combining LUS to DL in patients with proximal BC., Methods: Inclusion criteria were all patients affected by proximal BC undergone DL + LUS based on the following criteria: preoperative diagnosis of gallbladder cancer, hilar cholangiocarcinomas (HC) and borderline resectable intrahepatic cholangiocarcinoma (IHC). The overall yield (OY) and accuracy (AC) of DL ± LUS in determining unresectable disease were calculated., Results: From 01/2006 to 12/2014, 107 out of 191 (56%) potentially resectable proximal BC were evaluated. One hundred patients fulfilled inclusion criteria: 44 IHC, 21 GC and 35 HC. Forty-eight (48%) patients were male with median age of 65 (41-87) years. The median number of preoperative imaging was 3 ± 0.99. Patients underwent DL + LUS 10.5 ± 15.6 days after last imaging. DL + LUS identified unresectable diseases in 24 patients, 6 (25%) of them only thanks to LUS findings (3 GC and 3 IHC). At laparotomy, 6 (4 HC and 2 GC) out of 76 patients were found unresectable because of carcinomatosis (n = 2), new liver metastasis (n = 2) and vascular invasion (n = 2). LUS increased the OY (from 18 to 24%) and AC (from 60 to 80%) in the whole group. The advantages of LUS were confirmed for GC (OY from 38.1 to 52.4%, AC from 61.5 to 84.6%) and IHC patients (OY from 11.4 to 18.2%, AC from 62.5 to 100%) but not for HC group. The presence of biliary drainage was the only factor able to predict negative yield (p < 0.001)., Conclusions: LUS increases overall yield and accuracy of DL for detecting unresectable disease in patients with preoperative diagnosis of gallbladder cancer and borderline resectable intrahepatic cholangiocarcinomas.

Background: Outcomes in obese patients who underwent liver resection have been analyzed, but series are heterogeneous and data are controversial. The aim of this study was to analyze short-outcome in obese patients undergone hepatectomy for colorectal metastases., Study Design: A retrospective analysis on 1,021 consecutive hepatectomies between January 2000 and April 2014 for colorectal metastases was carried out. World Health Organization Classification of obesity (body mass index >30 kg/m(2)) was used to identify 140 obese patients. Outcomes were compared among obese and nonobese patients., Results: Obese patients were mainly male (78%) and were associated more frequently with hypertension (51% vs 29%, P < .001), ischemic heart disease (9% vs 3%, P = .007), and diabetes (23% vs 10%, P < .001) compared with nonobese patients. Approximately 30% of patients underwent major hepatectomy in the 2 groups. Associated resections were performed in 36% of obese and 37% of nonobese patients. Median parenchymal transection time (80 ± 64 minutes vs 70 ± 50 minutes, P = .013) and blood loss (300 ± 420 vs 200 ± 282, P = .001) were greater in obese patients. Postoperative mortality was nil in obese patients and 0.6% in nonobese patients. Overall morbidity was greater in obese patients (41% vs 31%, P = .012) mainly related to pulmonary complications (16% vs 9%, P = .012). Reinterventions were more frequent in obese patients (3.6% vs 1.2%, P = .004). Median hospital stay was comparable. At pathologic examination, hepatic steatosis was greater in obese (69% vs 43%, P < .001). At multivariate analysis, age >65 years (odds ratio [OR] 1.43, 95% confidence interval [95% CI] 1.09-1.88), obesity (OR 1.64, 95% CI 1.13-2.38), major hepatectomies (OR 1.65, 95% CI 1.31-2.33), and associated resections (OR 1.67, I95% CI 1.27-2.20) were independent predictors of overall morbidity (P < .001). Among obese patients, there was a positive correlation between age and severity of complications (R = 0.173, P = .041)., Conclusion: Obese patients undergoing hepatectomy for colorectal metastases should be approached with caution because of an increased risk of postoperative morbidity., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Nodular regenerative hyperplasia (NRH) is a severe form of chemotherapy-related liver injury (CALI) that may worsen the short-term outcome of liver resection (LR) for colorectal metastases (CRLM). The present study aimed to clarify the incidence, risk factors, preoperative assessment, and clinical impact of NRH., Methods: Overall, 406 patients undergoing 478 LRs for CRLM after chemotherapy between 2000 and 2012 were studied. All resection specimens were reviewed. After Gomori staining, NRH was graded according to the Wanless score., Results: NRH was diagnosed in 87 (18.2 %) patients, grades 2-3 in 14 (2.9 %) patients. At multivariate analysis, the prevalence of NRH was increased after oxaliplatin administration (21.4 vs. 8.4 %; p = 0.003), and reduced by the addition of bevacizumab (11.7 vs. 19.8 %; p = 0.020). Two parameters predicted the presence of NRH: the APRI score (AST to platelet ratio index: 25.5 % if >0.36 vs. 9.8 % if ≤0.36; p = 0.004), and the platelet count (63.6 % if <100 × 10(3)/mm(3) vs. 25.3 % if 100-200 × 10(3)/mm(3) vs. 11.9 % if >200 × 10(3)/mm(3); p = 0.032). Ninety-day mortality and liver failure rates were 0.6 and 3.6 %. NRH was an independent predictor of postoperative liver failure (9.2 % if present vs. 2.3 % if not present; p = 0.021). In patients with grades 2-3 NRH, the rate of liver failure was 14.3 %, 25.0 % after major hepatectomy. No other forms of CALI impacted short-term outcomes., Conclusions: NRH was the most relevant form of CALI, increasing the risk of postoperative liver failure. Oxaliplatin increased the incidence of NRH, while bevacizumab decreased it. The APRI score and platelet count were useful tools for predicting NRH.

Background: Portal vein occlusion (PVO) is used to increase inadequate future liver remnant volume (FLRV). Impaired liver regeneration has been reported in aged animals. This study was designed to evaluate the impact of patient age on hepatic regeneration., Methods: Sixty patients aged ≥70 years were matched 1:1 with 60 patients aged <70 years. Matching criteria were sex, diabetes, cirrhosis, pre-PVO chemotherapy and bevacizumab administration, and jaundice., Results: The median ages in the older and younger groups were 76 (range 70-83) years and 59 (range 20-69) years, respectively (p < 0.001). Median FLRV following PVO (33.1 ± 6.8 vs. 31.9 ± 6.0 %) and volumetric increase (0.52 ± 0.35 vs. 0.49 ± 0.34) were similar in the two groups. Of the older and younger patients, 10 % and 1.7 %, respectively, did not undergo liver surgery after PVO (p = 0.051). Mortality (5.5 vs. 6.7 %) and major morbidity (25.9.8 vs. 22 %) rates were similar. Liver failure rate was higher in older patients (35.1 vs. 16.9 %, p < 0.026), mainly due to Grade A liver failure (20.3 vs. 8.4 %, p < 0.001). Multivariate analysis showed that age ≥ 70 years [odds ratio (OR) 3.03; 95 % confidence interval (CI) 1.18-7.78; p = 0.020] and biliary cancer diagnosis (OR 4.69; 95 % CI 1.81-12.09; p = 0.001) were independent risk factors for postoperative liver failure., Conclusions: Liver regeneration after PVO is not impaired by age. Nevertheless, liver resection in elderly patients is performed less often after PVO and carries a higher risk of liver failure.

Laparoscopic liver surgery has gained widespread acceptance and nowadays it is suggested even for malignant disease. Although the benefits on short-term outcomes have been proven, data on oncological safety are still lacking. The aim of this study is to assess oncologic results after ultrasound-guided laparoscopic liver resection (LLR) or open liver resection (OLR) for colorectal metastases. 37 consecutive patients undergoing LLR between 01/2004 and 03/2014 were matched at a ratio of 1:1 with 37 OLR. Matching criteria were male sex, number and diameter of liver metastases, segment location, synchronous presentation, site and stage of primary tumor, positive lymph nodes of the primary, and concomitant extrahepatic disease. Demographic characteristics were similar among groups. Parenchymal transection time was longer in the LLR group (68 ± 38.2 SD vs 40 ± 33.7 SD, p = 0.01). Mortality was nil in LLR and OLR. Overall morbidity was significantly lower in LLR (13.5 vs 37.8%, p = 0.02), although severe complications were similar among the two groups. Patients undergoing LLR were discharged earlier (5 ± 2.3 SD vs 8 ± 6.6 SD days, p < 0.001). The median margin width was 5 (0-40) mm in LLR vs 8 (0-25) mm in OLR, p = 0.897. R1 resection was recorded in four LLR and three OLR (p = 1). Overall recurrences were similar among groups. Eight patients with hepatic or extrahepatic recurrence among LLR underwent surgery vs four of OLR (p = 0.03). After a median follow-up of 35.7 months in LLR and 47.9 months in OLR, 3-year overall survival was 91.8% LLR and 74.8% OLR (p = 0.14). 3-year disease-free survival was 69.1% LLR and 65.9% OLR (p = 0.53). Multivariate analysis showed that postoperative complications [HR 3.42 (95% CI 1.32-8.89)] and multiple metastases [HR 3.84 (95% CI 1.34-10.83)] were independent predictors of worse survival (p = 0.01). Ultrasound-LLR for colorectal hepatic metastases is safe, ensuring oncologic outcomes comparable to OLR.

Background: Lymph node (LN) status is one of the strongest prognostic factors after gallbladder cancer (GBC) resection. The adequate extension of LN dissection and the stratification of the prognosis in N+ patients have been debated. The present study aims to clarify these issues., Methods: A total of 112 consecutive patients who underwent operations for GBC with LN dissection were analyzed. Twenty-five patients (22.3%) had D1 dissection (hepatic pedicle), and 87 (77.7%) had D2 dissection (hepatic pedicle, celiac and retro-pancreatic area). The LN ratio (LNR) was computed as follows: number of metastatic LNs/number of retrieved LNs., Results: The median number of retrieved LNs was 7 (1-35). Fifty-nine patients (52.7%) had LN metastases (22 N2). D2 dissection allowed the retrieval of more LNs (8 vs. 3, p = 0.0007), with similar short-term outcomes. Common bile duct (CBD) resection (n = 41) did not increase the number of retrieved LNs. In five patients, D2 dissection identified skip LN metastases that otherwise would have been missed. LN metastases negatively impacted survival (5-years survival 57.2% if N0 vs. 12.4% if N+, p < 0.0001), but N1 and N2 patients had similar survival rates. The number of LN+ (1-3 vs. ≥4) did not impact prognosis. An LNR = 0.15 stratified the prognosis of N+ patients: 5-years survival 32.7% if LNR ≤ 0.15 vs. 10.3% if LNR > 0.15 (multivariate analysis p = 0.007)., Conclusions: A D2 LN dissection is recommended in all patients, because it allows for better staging. CBD resection does not improve LN dissection. An LNR = 0.15, not the site of metastatic LNs, stratified the prognoses of N+ patients.

Background: The present study was designed to evaluate the role of intraoperative ultrasound (IOUS) in intrahepatic staging and the impact on surgical strategy for patients with colorectal liver metastases (CRLM)., Methods: The study included 515 patients who had undergone liver resection for CRLM at two tertiary care referral centers. Data from a prospectively collected database were retrospectively analysed. Early intrahepatic recurrence was assessed at 3 and 6 months after resection and was considered as residual disease undetected by IOUS. Performance of imaging modalities was compared by analysis of studies on individual patients., Results: A total of 1,370 liver metastases were detected preoperatively with a median of 3 imaging modalities. MRI and PET were performed in 51 and 42 % of the patients, respectively. Median number of days between last imaging and surgery was 18. Contrast-enhanced IOUS was performed in 136 patients (26.4 %). Intraoperatively, 293 new nodules were found in 132 patients: on histology 280 were CRLM (17.6 %). Surgical strategy was changed in 140 patients (27.2 %). On multivariate analysis synchronous and bilobar metastases ≥ 3 in number, BMI ≥ 30, and time between last imaging and surgery longer than 18 days resulted in predictive factors indicating new nodules detected by IOUS. Early intrahepatic recurrences were 3.7 and 7.9 % at 3 and 6 months. Performance of CT, MRI, FDG-PET, and intraoperative staging was compared: sensitivity was 63.6, 68.8, 53.6, and 92 % and specificity was 91, 92.3, 95.8, and 97.8 %, respectively, Conclusions: The use of IOUS continues to be mandatory for correct staging of patients with CRLM undergoing liver resection.

Objectives: To determine which method of liver volumetry is more accurate in predicting a safe resection., Background: Before major or extended hepatectomy, assessment of the future liver remnant (FLR) is crucial to reduce the risk of postoperative hepatic insufficiency. The FLR volume is usually expressed as the ratio of FLR to nontumorous total liver volume (TLV), which can be measured directly by computed tomography (mTLV) or estimated (eTLV) on the basis of correlation existing with the body surface area. To date, these 2 methods have never been compared., Methods: All consecutive, noncirrhotic patients who underwent resection of 3 or more liver segments between April 2000 and April 2012 and for whom (i) preoperative computed tomographic scans and (ii) body surface area were available entered the study. The mTLV (calculated as TLV - tumor volume) was compared with the eTLV (calculated as -794.41 + 1267.28 × body surface area) using volumetric data (cm) and clinical outcome measures (specifically, hepatic insufficiency and 90-day mortality). Definition of hepatic insufficiency was peak postoperative serum total bilirubin level of more than 7 mg/dL or, in jaundiced patients, an increasing bilirubin level on day 5 or thereafter., Results: Two-hundred forty-three patients who had undergone major (n = 135) or extended (n = 108) hepatectomies met the inclusion criteria. Twenty-eight patients (11.5%) developed hepatic insufficiency, whereas 7 patients (2.9%) died postoperatively. Compared with the eTLV, the mTLV underestimated the liver volume in 60.1% of the patients (P < 0.01). Forty-seven and 73 patients had an inadequate FLR based on mTLV and eTLV, respectively. Portal vein occlusion (PVO) was used in 44 patients. In patients (n = 162) in whom both methods did not evidence the need for PVO, postoperative hepatic insufficiency and mortality were 4.9% and 0.6%, respectively. Conversely, in patients (n = 27) in whom the eTLV but not the mTLV evidenced the need for PVO, and thus PVO was not performed, hepatic insufficiency (22.2%; P = 0.001) and mortality (3.7%; P = ns) were higher., Conclusions: The use of eTLV identifies a subset of patients (∼11%) in whom liver volumetry with the mTLV underestimates the risk of hepatic insufficiency.

Background: Management of patients with synchronous colorectal liver metastases (SCRLM) should be individually tailored. This study compares patients managed by hepatobiliary centers from diagnosis with those referred for liver resection (LR)., Methods: Between 1998 and 2010, a total of 284 patients with SCRLM underwent resection; 106 resectable patients (1-3 unilobar metastases, diameter <100 mm, liver-only disease) were divided into two groups: 66 managed from diagnosis (group A) and 40 referred for LR (group B)., Results: Group A contained a greater proportion of multiple metastases (55.0 vs. 34.8%, P = 0.042). Group B always received colorectal surgery as up-front treatment (vs. 18.2%, P < 0.0001). In group B, chemotherapy before LR was more common (72.5 vs. 33.3%, P = 0.0001) and lasted longer (P = 0.010). More patients in group B exhibited disease progression before LR (17.5 vs. 3.0%, P = 0.025). Group A underwent fewer surgical procedures (80.3% simultaneous resection vs. 0%, P < 0.00001), with similar short-term outcomes. After a median follow-up of 42.0 months, group A exhibited higher 5 year disease-free survival (DFS, 64.8 vs. 30.8%, P = 0.005) and fewer extrahepatic recurrences (21.5 vs. 47.5%, P = 0.005). The late-referral group (>6 months, n = 24) had shorter median overall survival (OS) and DFS than group A (49.1 and 25.3 months vs. not achieved and not achieved, P < 0.05). The early-referral group exhibited OS and DFS similar to group A. Multivariate analysis confirmed late referral as a negative predictive factor of OS and DFS., Conclusions: Monocentric management of SCRLM in hepatobiliary centers is associated with shorter preoperative chemotherapy, better disease control, fewer surgical procedures (simultaneous resection), and, compared with late-referred patients, better survival.

Trial Design: A prospective randomised controlled trial was designed to evaluate the advantages of routine application of the anterior approach during right hepatectomy., Methods: The study was conducted between March 2005 and April 2009 in a tertiary hepatobiliary-pancreatic centre. Patients scheduled for right hepatectomy for primary or metastatic tumours, without infiltration of segment 1, inferior vena cava or main bile duct, were randomly assigned to right hepatectomy using either an anterior or a classic approach. The primary study endpoint was overall blood loss., Results: Sixty-six patients were randomly allocated to undergo right hepatectomy with an anterior (AA group n=33) or a classic approach (CA group n=33). Sixty-five patients were included in the analysis (33 in AA group and 32 in CA group). There was no significant difference in patient age, diagnosis, preoperative hepatic biochemistry and tumour size between the two groups. Overall blood loss (437 ml ± 664 in AA group vs.500 ml ± 532.3 in CA group; p=0.960) and bleeding during transection (p=0.973) were similar between two groups. Perioperative blood transfusion rates were 18% in the AA group and 9.3 % in the CA group (p=0.253). Time of parenchymal transsection was significantly longer in AA group (75.1 ± 26.6 min vs. 56.7 ± 17.5 min, p=0.01). There was no difference between both groups for postoperative prothrombin time, serum transaminase and total bilirubin levels. One patient died in each group (p=0.746). The two groups had similar morbidity rates., Conclusion: Routine application of the anterior approach during right hepatectomy does not decrease intraoperative blood loss and morbidity rate.

Background: Liver resection (LR) is the only potentially curative treatment of colorectal liver metastases (CRLM). Its outcome over the past 2 decades was studied using actual 5-year survival rates., Methods: Data of 393 consecutive patients who underwent LR for CRLM at Mauriziano Umberto I (Turin) until June 2005 were analyzed. Excluding R2 resections (n = 4) or incomplete 5-year follow-up (n = 13), 376 patients were divided according to LR date into groups A (before 1995: 90 patients), B (1995-2000: 94 patients), C (2001-2005: 192)., Results: Group C presented increased multiple and bilobar metastases compared with combined group A and B (C vs AB: 54.7% vs 40.2%, P = 0.005; 28.1% vs 19.0%, P = 0.038, respectively), decreased metastases diameter (C vs AB: 32 vs 40 mm, P = 0.0001). The 5-year overall survival, calculated excluding 4 operative mortalities (group AB), increased over the years (A, 20.5%; B, 32.6%; C, 46.4%; P < 0.0001). Early recurrences (1 year) were not decreased, extrahepatic recurrences even increased (C vs AB: 17.2% vs 8.6%, P = 0.015). Recurrence-free 5-year survival improved (C vs AB: 23.4% vs 13.9%, P = 0.019) linked to decreased liver recurrences (C vs AB: 26.8% vs 37.4%, P = 0.023). Resection rate (59% overall for liver recurrence) increased along with 5-year survival after recurrence (A, 4.0%; B, 14.2%; C, 21.4%; P < 0.0001). Survival improvement was confirmed for multiple (P = 0.003) and synchronous metastases (P = 0.008), N+ tumors (P = 0.005), and in patients without chemotherapy (P = 0.001)., Conclusions: Long-term outcome of LR for CRLM improved over 20 years, even in patients with negative prognostic factors, linked to hepatic recurrences reduction and increased survival after recurrence.

Purpose: The aim of this study was to evaluate the intraoperative detection rate of residual liver metastases after chemotherapy and to assess the correlation between disappeared liver metastases (DLMs) upon preoperative imaging and complete pathological response., Methods: Between February 2004 and December 2008 clinicopathological data of 292 consecutive patients who underwent liver resection for colorectal liver metastases were prospectively collected and analyzed in a "per lesion" study. Thirty-three patients with 67 DLMs were included., Results: During laparotomy, we identified 45 out of 67 DLMs (67%). Six DLMs were detected by macroscopic liver examination (9%) and 39 (58%) by intraoperative ultrasound (IOUS). Overall, persistent microscopic residual disease at pathological examination of the resected specimen or recurrence in situ identified during the follow-up were observed in 41 (61.2%) of 67 LMs that had shown a complete response by imaging. At multivariate analysis moderate or severe hepatic steatosis (p = 0.016), subglissonian localization of nodules (p = 0.019) and residual microscopic disease (p = 0.0006) were associated with IOUS detection of residual metastases. Preoperative chemotherapy with more than six cycles (p = 0.022) and intraoperative detection of nodules by IOUS (p = 0.001) were independent predictors of residual disease., Conclusions: Systematic US exploration of the liver leads to increase the intraoperative detection rate of DLMs. Furthermore, the majority of DLMs identified by IOUS presents residual disease at pathological examination and should be treated.

Background: Pedicle clamping during liver resection (LR) is debated. The purpose of this study is to validate non-clamping policy across a large series of LR and to evaluate the need for salvage clamping (SC) and its outcomes., Methods: Five hundred twelve consecutive LR without initial pedicle clamping performed between 2004 and 2009 were analyzed., Results: Among 512 LR (171 major hepatectomies), 90.2% were completed without clampage. Fifty (9.8%) required SC. Blood loss were higher in SC group (555 vs. 175 mL, p < 0.0001), while transfusion rate was not. No differences were observed in terms of mortality (0%/1.3%), morbidity (38%/38.3%), liver dysfunction (4%/3.7%), and renal dysfunction (0%/1.3%). Bile leak rate was increased in the SC group (20%/10.2%, p = 0.036). At multivariate analysis, three predictive factors of SC were identified: arterial hypertension (p = 0.007, SC rate = 13%), cirrhosis (p = 0.003, SC rate = 26%), and LR conducted along the right portal scissure (p = 0.010, SC rate = 32%). One protective factor was identified: LR confined to antero-lateral segments (Sg2-6, p = 0.001, SC rate  = 2%). Extension of LR had no impact on need for SC., Conclusions: The majority of LR can be safely performed without clamping with excellent outcomes. SC is a safe procedure and does not worsen postoperative outcomes, except for bile leak rate. Clamping policy should be tailored to the type of LR and presence of cirrhosis.

Recent advances in patient selection and surgical technique have resulted in low mortality and morbidity rates after liver resections. The aim of this study was to evaluate the operative risks of liver trisectionectomies in comparison with major resections. The data prospectively collected of patients who underwent trisectionectomies (TR Group, n = 54) and major hepatectomies (MH Group, n = 175) without biliary reconstruction were compared. Besides, the early results of patients who underwent right trisectionectomies (RTR Group, n = 36) and left trisectionectomies (LTR Group, n = 18) were compared. There was no significant difference in patient characteristics of MH and TR groups excluded for a high portal vein embolization (PVE) in TR group. Mortality (1% in MH group and 3.7% in TR group, p = 0.206) and overall morbidity rates (39% in MH group and 48% in TR group, p = 0.225) were similar between two groups. A higher proportion of patients in TR group developed liver failure (p = 0.024) and required blood transfusion (30 vs. 11%, p < 0.001). The median hospital stay after trisectionectomies was higher in TR group than MH group (p = 0.053). There was no significant difference in patient characteristics of LTR and RTR groups excluded for lymphadenectomy which was higher in LTR group (p = 0.008) and PVE rate higher in RTR group (p = 0.01). The overall morbidity (44 vs. 55%) and mortality (2.7 vs. 5.5%) were comparable between two groups. A higher proportion of patients in RTR group required blood transfusion (39 vs. 11%, p = 0.032). At multivariate analysis, age was the only positive predictor for morbidity after trisectionectomies (p = 0.010). Trisectionectomies can be performed safely. Left trisectionectomies are as safe as right trisectionectomies. The accurate preoperative selection is necessary to reduce operative risks.

Background: Optimal margin width is uncertain because of conflicting results from recent studies using overall survival as the end-point. After recurrence, re-resection and aggressive chemotherapy heavily affect survival time; the potential confounding effect of such factors has not been investigated. Use of recurrence-free survival (RFS) may overcome this limitation. The aim of this study is to evaluate the impact of width of resection margin on RFS and site of recurrence after hepatic resection for colorectal metastases (CRM)., Methods: From a prospectively maintained institutional database (1/1999-12/2007) we identified 314 patients undergone hepatectomy for CRM (1/1999-12/2007) with detailed pathologic analysis of the surgical margin and complete follow-up imaging studies documenting disease status and site of recurrence, which was categorized as: resection margin (M(arg)), other intra-hepatic ((other)IH), lung (L) or other extra-hepatic ((other)EH). Recurrence-free estimation was the survival end-point., Results: Median follow-up was 56.5 months. Two hundred and fifteen patients (68.8%) recurred at 288 sites after a mean of 15.5 months. A positive resection margin was associated with an increased risk of M(arg) recurrence (P < 0.001). The presence of >or=2 metastases was the only factor increasing the risk of positive margins (P < 0.05). The width of the negative resection margin (>or=1 cm versus >1 cm) was not a prognostic factor of worse RFS (30.2% versus 37.3%, P = 0.6). Node status of the primary tumour, and size and number of CRM were independent predictors of RFS., Conclusions: Tumour biology and not the width of the negative resection margin affect RFS.

Integrative biomedical research projects query, analyze, and integrate many different data types and make use of datasets obtained from measurements or simulations of structure and function at multiple biological scales. With the increasing availability of high-throughput and high-resolution instruments, the integrative biomedical research imposes many challenging requirements on software middleware systems. In this paper, we look at some of these requirements using example research pattern templates. We then discuss how middleware systems, which incorporate Grid and high-performance computing, could be employed to address the requirements.

The field of informatics has been going through a rapid change over the past decade. New technologies such as grid computing[1-5] and knowledge anchored data, combined with major funding and growing community thrusts aimed at creating a richer multi-institutional research and clinical environment such as caBIG™[6-8] (Cancer Bioinformatics Grid), BIRN[9] (Bioinformatics Research Network), and CTSA(Clinical and Translational Science Awards) have lead to new ways to bring together information across institutional boundaries. This had lead to service oriented architectures based developments in creating semantically interoperable data and analytical services to increase speed, efficiency, and outcome of clinical and research efforts spanning the fields of medicine. The TRIAD (Translational Informatics and Data Management Grid) System, which will be used as the middleware system enabling the OSU CTSA to create a scalable, secure, and knowledge anchored data sharing environment, will adopt and adapt the caGrid infrastructure designed for the caBIG™ program.

Design templates that involve discovery, analysis, and integration of information resources commonly occur in many scientific research projects. In this paper we present examples of design templates from the biomedical translational research domain and discuss the requirements imposed on Grid middleware infrastructures by them. Using caGrid, which is a Grid middleware system based on the model driven architecture (MDA) and the service oriented architecture (SOA) paradigms, as a starting point, we discuss architecture directions for MDA and SOA based systems like caGrid to support common design templates.

We present the implementation of an application using caGrid, which is the service-oriented Grid software infrastructure of the NCI cancer Biomedical Informatics Grid (caBIG), to support design and analysis of custom microarray experiments in the study of epigenetic alterations in cancer. The design and execution of these experiments requires synthesis of information from multiple data types and datasets. In our implementation, each data source is implemented as a caGrid Data Service, and analytical resources are wrapped as caGrid Analytical Services. This service-based implementation has several advantages. A backend resource can be modified or upgraded, without needing to change other components in the application. A remote resource can be added easily, since resources are not required to be collected in a centralized infrastructure.

caGrid is a middleware system which combines the Grid computing, the service oriented architecture, and the model driven architecture paradigms to support development of interoperable data and analytical resources and federation of such resources in a Grid environment. The functionality provided by caGrid is an essential and integral component of the cancer Biomedical Informatics Grid (caBIG) program. This program is established by the National Cancer Institute as a nationwide effort to develop enabling informatics technologies for collaborative, multi-institutional biomedical research with the overarching goal of accelerating translational cancer research. Although the main application domain for caGrid is cancer research, the infrastructure provides a generic framework that can be employed in other biomedical research and healthcare domains. The development of caGrid is an ongoing effort, adding new functionality and improvements based on feedback and use cases from the community. This paper provides an overview of potential future architecture and tooling directions and areas of improvement for caGrid and caGrid-like systems. This summary is based on discussions at a roadmap workshop held in February with participants from biomedical research, Grid computing, and high performance computing communities.

caGrid is the core Grid architecture of the NCI-sponsored cancer Biomedical Informatics Grid (caBIG) program. The current release, caGrid version 1.0, is developed as the production Grid software infrastructure of caBIG. Based on feedback from adopters of the previous version (caGrid 0.5), it has been significantly enhanced with new features and improvements to existing components. This paper presents an overview of caGrid 1.0, its main components, and enhancements over caGrid 0.5.

Security is a high priority issue in medical domain, because many institutions performing biomedical research work with sensitive medical data regularly. This issue becomes more complicated, when it is desirable or needed to access and analyze data in a multi-institutional setting. In the NCI cancer Biomedical Informatics Grid (caBIG) program, several security issues were raised that existing security technologies could not address. Considering caBIG is envisioned to span a large number of cancer centers and investigator laboratories, these issues pose considerable challenge. In this paper we present these issues and the infrastructure, referred to as GAARDS, which has been developed to address them.

The use of rules-engines spans multiple computational and biomedical domains. Within the NCIs caBIG program, the orchestration of grid-based computational workflow has used the BPEL standard. However, recent strategic planning within caBIG has raised questions about the applicability of BPEL for other rule definition and execution scenarios. In response, we have reviewed the current state of rules-engine technologies, and have formulated an architectural model for the integration of heterogeneous rules-engines with caGrid.

This paper describes a Grid-aware image reviewing system (GridIMAGE) that allows practitioners to (a) select images from multiple geographically distributed digital imaging and communication in medicine (DICOM) servers, (b) send those images to a specified group of human readers and computer-assisted detection (CAD) algorithms, and (c) obtain and compare interpretations from human readers and CAD algorithms. The currently implemented system was developed using the National Cancer Institute caGrid infrastructure and is designed to support the identification of lung nodules on thoracic computed tomography. However, the infrastructure is general and can support any type of distributed review. caGrid data and analytical services are used to link DICOM image databases and CAD systems and to interact with human readers. Moreover, the service-oriented and distributed structure of the GridIMAGE framework enables a flexible system, which can be deployed in an institution (linking multiple DICOM servers and CAD algorithms) and in a Grid environment (linking the resources of collaborating research groups). GridIMAGE provides a framework that allows practitioners to obtain interpretations from one or more human readers or CAD algorithms. It also provides a mechanism to allow cooperative imaging groups to systematically perform image interpretation tasks associated with research protocols.

Motivation: The complexity of cancer is prompting researchers to find new ways to synthesize information from diverse data sources and to carry out coordinated research efforts that span multiple institutions. There is a need for standard applications, common data models, and software infrastructure to enable more efficient access to and sharing of distributed computational resources in cancer research. To address this need the National Cancer Institute (NCI) has initiated a national-scale effort, called the cancer Biomedical Informatics Grid (caBIGtrade mark), to develop a federation of interoperable research information systems., Results: At the heart of the caBIG approach to federated interoperability effort is a Grid middleware infrastructure, called caGrid. In this paper we describe the caGrid framework and its current implementation, caGrid version 0.5. caGrid is a model-driven and service-oriented architecture that synthesizes and extends a number of technologies to provide a standardized framework for the advertising, discovery, and invocation of data and analytical resources. We expect caGrid to greatly facilitate the launch and ongoing management of coordinated cancer research studies involving multiple institutions, to provide the ability to manage and securely share information and analytic resources, and to spur a new generation of research applications that empower researchers to take a more integrative, trans-domain approach to data mining and analysis., Availability: The caGrid version 0.5 release can be downloaded from https://cabig.nci.nih.gov/workspaces/Architecture/caGrid/. The operational test bed Grid can be accessed through the client included in the release, or through the caGrid-browser web application http://cagrid-browser.nci.nih.gov.

Diverse data sets have become key building blocks of translational biomedical research. Data types captured and referenced by sophisticated research studies include high throughput genomic and proteomic data, laboratory data, data from imagery, and outcome data. In this paper, the authors present the application of an XML-based data management system to support integration of data from disparate data sources and large data sets. This system facilitates management of XML schemas and on-demand creation and management of XML databases that conform to these schemas. They illustrate the use of this system in an application for genotype-phenotype correlation analyses. This application implements a method of phenotype-genotype correlation based on phylogenetic optimization of large data sets of mouse SNPs and phenotypic data. The application workflow requires the management and integration of genomic information and phenotypic data from external data repositories and from the results of phenotype-genotype correlation analyses. Our implementation supports the process of carrying out a complex workflow that includes large-scale phylogenetic tree optimizations and application of Maddison's concentrated changes test to large phylogenetic tree data sets. The data management system also allows collaborators to share data in a uniform way and supports complex queries that target data sets.

Laparoscopic surgery is a relatively new option for the treatment of hepatocellular carcinoma (HCC) on cirrhosis. To date, there have been only a few reports of this option for this pathology in the literature, probably because of the intra operative difficulties related to the treatment of this pathology (even at laparotomy) and because of the problems related to the minimally invasive approach (technical difficulties, complicated management of the bleeding, lack of dedicate tools, and fear of gas embolism). In this article we report four patients from our whole series (23 laparoscopic liver resections for HCC) who underwent a laparoscopic resection for completely exophytic HCC on cirrhosis, located in segment IV in two patients, and in segment III and segment V respectively, in the other two. The mean operative time was 116 min (range, 90-150 min). The Pringle maneuver was never performed. No blood transfusions were needed. No postoperative complications occurred, neither ascites, nor jaundice, nor encephalopathy. Postoperative liver function returned to the preoperative level within 3 days. Food intake started on postoperative day 2. The patients were discharged on postoperative days 5 (one patient), 6 (two patients), and 7 (one patient) after uncomplicated courses. In our opinion, limited laparoscopic liver resections could be considered, at present, to be the best option for the treatment of extremely rare protruding HCC on cirrhosis. We believe that a minimally invasive approach can minimize the postoperative morbidity rate, which is still too high in this group of patients. Our experience confirmed that nonanatomical limited resections or anatomical left lateral segmentectomies for HCC on cirrhosis are feasible and safe in the hands of surgeons trained in both open liver surgery and advanced laparoscopic surgery.

Sixty patients with type I diabetes mellitus underwent an ergometric stress test (EST) to evaluate the relationship between cardiac autonomic neuropathy (CAN) and hemodynamic changes during EST. All patients were divided into 2 groups: in the Group A were included 26 patients (mean age 43 +/- 9 years) with impairment of 2 or more autonomic tests according to Ewing (patients with CAN) and in the Group B were included 34 patients (mean age 38 +/- 13 years) without CAN. The EST was symptom-limited and performed with load increases of 25 W every 3 min. No positive EST were observed in both groups. Heart rate (HR) at rest and systolic blood pressure (SBP) at maximum common workload were significantly higher in Group A than in Group B. Moreover, a significant linear correlation was found between a CAN score and SBP x HR product at rest and at maximal workload. These findings are correlated with increased sympathetic activity due to a parasympathetic impairment. The data show the relationship between hemodynamic changes during EST and the Ewing test used in the diagnosis of CAN.

The diagnostic utility of an abnormal decrease in systolic blood pressure (PAS) after exercise, have been evaluated by an index obtained by the ratio between PAS at the maximal stage of exercise and PAS at the 1', 3' and 5' of recovery (PAS index). The 58 patients studied have been divided in two groups: group A, 32 patients, aged 33-66 (means 51.5) with angina pectoris and significant coronary stenosis; group B, 26 subjects, aged 27-39 (mean 34.7), asymptomatic, without coronary stenosis (control group). PAS index at 1' of recovery have been 0.82 +/- 0.08 in the group B and 0.94 +/- 0.07 in the group A (p less than 0.0005); at the 3' of recovery 0.72 +/- 0.07 in the group B and 0.86 +/- 0.11 in CAD group (p less than 0.0005); at 5' of recovery 0.66 +/- 0.07 in the group B and 0.79 +/- 0.11 in the group A (p less than 0.0005). Diagnostic accuracy have been of 60%, 75% and 75% for PAS index respectively at first, third and fifth minute of recovery, while ST depression diagnostic accuracy have been of 88%.

In 13 patients, affected by hypertrophic obstructive cardiomyopathy (HOCM) and essential hypertension, antihypertensive-efficacy and effects of a new calcium-channel blocker (gallopamil) associated with a diuretic agent (chlorthalidone) on left ventricular systolic and diastolic performance assessed by phonocardiographic methods. The results were compared to those obtained, in the same group of patients, with a selective beta-blocker (atenolol) associated with the same diuretic agent (chlorthalidone). With both therapeutic regimens a statistically significant reduction of systolic and diastolic arterial pressure was observed; both agents were able to reduce hemodynamic gradient in systole which characterize HOCM; however, the treatment with gallopamil plus chlorthalidone determined greater effects on left ventricular diastolic function as compared to the treatment with atenolol plus chlorthalidone; both treatments determined bradycardia.