Neoadjuvant chemotherapy for initially unresectable intrahepatic cholangiocarcinoma.

BACKGROUND: Locoregional extension of intrahepatic cholangiocarcinoma (ICC) at the time of diagnosis results in a low resectability rate and poor prognosis. The aim of this retrospective study was to assess the efficacy of neoadjuvant chemotherapy for locally advanced ICC. METHODS: All consecutive patients with ICC between 2000 and 2013 were included prospectively in a single-centre database and analysed retrospectively. Patients with locally advanced ICC considered as initially unresectable received primary chemotherapy, followed by surgery in those with secondary resectability. Results of patients who underwent surgery for locally advanced ICC were compared with those of patients with initially resectable ICC treated by surgery alone. RESULTS: A total of 186 patients were included in the study. Of 74 patients with locally advanced ICC, 39 (53 per cent) underwent secondary resection after a median of six chemotherapy cycles. Patients in this group were younger (P = 0·030) and had more advanced disease than those who had surgery alone, and presented more frequently with lymphadenopathy (P = 0·010) and vascular invasion (P = 0·010). Postoperative morbidity and mortality were no different between the groups. The median survival of patients who had surgery after chemotherapy was 24·1 months, and that of patients who had surgery alone was 25·7 months (P = 0·391). CONCLUSION: Patients with locally advanced ICC treated by surgery following neoadjuvant chemotherapy had similar short- and long-term results to patients with initially resectable ICC who had surgery alone. Neoadjuvant chemotherapy as a first-line treatment for locally advanced ICC may be an effective downstaging option, facilitating secondary resectability in patients with initially unresectable disease.

Neoadjuvant chemotherapy response influences outcomes in non-colorectal, non-neuroendocrine liver metastases.

BACKGROUND: Indications for surgical resection of non-colorectal, non-neuroendocrine (NCNNE) liver metastases are unclear. This study analysed the influence of response to neoadjuvant chemotherapy and the presence of extrahepatic disease (EHD) on outcomes. METHODS: Patients who underwent hepatic resection for NCNNE liver metastases and who received neoadjuvant chemotherapy at a single centre between 1982 and 2016 were analysed retrospectively. Patients were classified as having no EHD, controlled EHD or non-controlled EHD. RESULTS: Hepatic resection was performed in 199 patients (81·2 per cent) after partial or complete response to chemotherapy or disease stabilization, and 46 patients (18·8 per cent) after tumour progression. Patients with progressive disease after chemotherapy had worse overall survival than those without (23 versus 50·4 per cent at 5 years; P = 0·004). Median survival was 63·6 (range 31·1-94·8) months for patients without EHD, 34·8 (19·2-49·2) months for those with controlled EHD and 7·2 (1·2-13·2) months for patients with non-controlled EHD (P = 0·004). In multivariable analysis, EHD (P = 0·004), response to chemotherapy (P = 0·004) and resection margins (P = 0·002) were all independent predictors of overall survival, regardless of primary tumour site. CONCLUSION: The prognosis of patients with NCNNE liver metastases is influenced by preoperative chemotherapy and resectability.

Outcomes of surgical shunts and transjugular intrahepatic portasystemic stent shunts for complicated portal hypertension.

BACKGROUND: Transjugular intrahepatic portasystemic stent shunt (TIPSS), instead of surgical shunt, has become the standard treatment for patients with complicated portal hypertension. This study compared outcomes in patients who underwent TIPSS or surgical shunting for complicated portal hypertension. METHODS: This was a retrospective study of all consecutive patients who received portasystemic shunts from 1994 to 2014 at a single institution. Patients who underwent surgical shunting were compared with those who had a TIPSS procedure following one-to-one propensity score matching. The primary study endpoints were overall survival and shunt failure, defined as major variceal rebleeding, relapse of refractory ascites, irreversible shunt occlusion, liver failure requiring liver transplantation, or death. RESULTS: A total of 471 patients received either a surgical shunt or TIPSS. Of these, 334 consecutive patients with cirrhosis who underwent elective surgical shunting (34) or TIPSS (300) for repeated variceal bleeding or refractory ascites were evaluated. Propensity score matching yielded 31 pairs of patients. There were no between-group differences in morbidity and 30-day mortality rates. However, shunt failure was less frequent after surgical shunting than TIPSS (6 of 31 versus 16 of 31; P = 0·016). The 5-year shunt failure-free survival (77 versus 15 per cent; P = 0·008) and overall survival (93 versus 42 per cent; P = 0·037) rates were higher for patients with surgical shunts. Multivariable analysis revealed that a Model for End-Stage Liver Disease (MELD) score exceeding14 and TIPSS were independently associated with shunt failure. In patients with MELD scores of 14 or less, the 5-year overall survival rate remained higher after surgical shunting than TIPSS (100 versus 40 per cent; P < 0·001). CONCLUSION: Surgical shunting achieved better results than TIPSS in patients with complicated portal hypertension and low MELD scores.

Long-term outcomes of radiofrequency ablation combined with hepatectomy compared with hepatectomy alone for colorectal liver metastases.

BACKGROUND: Combining radiofrequency ablation (RFA) with hepatectomy may enable treatment with curative intent for patients with colorectal liver metastasis (CRLM). However, the oncological outcomes in comparison with resection alone remain to be clarified. METHODS: Patients who underwent a first hepatectomy between 2001 and 2012 for CRLM were enrolled. Short- and long-term outcomes of patients who underwent hepatectomy plus RFA were compared with those of patients who had hepatectomy alone using propensity score matching. RESULTS: Of a total of 553 patients, hepatectomy + RFA and hepatectomy alone were performed in 37 and 516 respectively. Before matching, patients in the hepatectomy + RFA group were characterized primarily by a larger tumour burden. After matching of 31 patients who underwent hepatectomy + RFA with 93 who had hepatectomy alone, background characteristics were well balanced. In the matched cohort, overall and disease-free survival in the hepatectomy + RFA group were no different from those among patients who had hepatectomy alone (5-year overall survival rate 57 versus 61 per cent, P = 0·649; 5-year disease-free survival rate 19 versus 17 per cent, P = 0·865). Local recurrence at the ablated site was observed in four of 31 patients (13 per cent). Although overall local recurrence (ablated site and/or cut surface) was more frequent in the hepatectomy + RFA group (9 of 31 (29 per cent) versus 11 of 93 (12 per cent); P = 0·032), there was no difference in intrahepatic disease-free survival between the two groups (P = 0·705). CONCLUSION: Hepatectomy + RFA achieved outcomes comparable to hepatectomy alone. Combining RFA with hepatectomy should be considered as an option to achieve cure.

Ad Integrum Functional and Volumetric Recovery in Right Lobe Living Donors: Is It Really Complete 1 Year After Donor Hepatectomy?

The partial liver's ability to regenerate both as a graft and remnant justifies right lobe (RL) living donor liver transplantation. We studied (using biochemical and radiological parameters) the rate, extent of, and predictors of functional and volumetric recovery of the remnant left liver (RLL) during the first year in 91 consecutive RL donors. Recovery of normal liver function (prothrombin time [PT] ≥70% of normal and total bilirubin [TB] ≤20 µmol/L), liver volumetric recovery, and percentage RLL growth were analyzed. Normal liver function was regained by postoperative day's 7, 30, and 365 in 52%, 86%, and 96% donors, respectively. Similarly, mean liver volumetric recovery was 64%, 71%, and 85%; whereas the percentage liver growth was 85%, 105%, and 146%, respectively. Preoperative PT value (p = 0.01), RLL/total liver volume (TLV) ratio (p = 0.03), middle hepatic vein harvesting (p = 0.02), and postoperative peak TB (p < 0.01) were predictors of early functional recovery, whereas donor age (p = 0.03), RLL/TLV ratio (p = 0.004), and TLV/ body weight ratio (p = 0.02) predicted early volumetric recuperation. One-year post-RL donor hepatectomy, though functional recovery occurs in almost all (96%), donors had incomplete restoration (85%) of preoperative total liver volume. Modifiable predictors of regeneration could help in better and safer donor selection, while continuing to ensure successful recipient outcomes.

Conversion to resection of liver metastases from colorectal cancer with hepatic artery infusion of combined chemotherapy and systemic cetuximab in multicenter trial OPTILIV.

BACKGROUND: Systemic chemotherapy typically converts previously unresectable liver metastases (LM) from colorectal cancer to curative intent resection in ∼15% of patients. This European multicenter phase II trial tested whether hepatic artery infusion (HAI) with triplet chemotherapy and systemic cetuximab could increase this rate to 30% in previously treated patients. PATIENTS AND METHODS: Participants had unresectable LM from wt KRAS colorectal cancer. Main non-inclusion criteria were advanced extra hepatic disease, prior HAI and grade 3 neuropathy. Irinotecan (180 mg/m(2)), oxaliplatin (85 mg/m(2)) and 5-fluorouracil (2800 mg/m(2)) were delivered via an implanted HAI access port and combined with i.v. cetuximab (500 mg/m(2)) every 14 days. Multidisciplinary decisions to resect LM were taken after every three courses. The rate of macroscopic complete resections (R0 + R1) of LM, progression-free survival (PFS) and overall survival (OS) were computed according to intent to treat. RESULTS: The patient population consisted of 42 men and 22 women, aged 33-76 years, with a median of 10 LM involving a median of six segments. Up to 3 extrahepatic lesions of <1 cm were found in 41% of the patients. A median of six courses was delivered. The primary end point was met, with R0-R1 hepatectomy for 19 of the 64 previously treated patients, 29.7% (95% confidence interval 18.5-40.9). Grade 3-4 neutropenia (42.6%), abdominal pain (26.2%), fatigue (18%) and diarrhea (16.4%) were frequent. Objective response rate was 40.6% (28.6-52.3). Median PFS and OS reached 9.3 (7.8-10.9) and 25.5 months (18.8-32.1) respectively. Those with R0-R1 hepatectomy had a median OS of 35.2 months (32.6-37.8), with 37.4% (23.6-51.2) alive at 4 years. CONCLUSION: The coordination of liver-specific intensive chemotherapy and surgery had a high curative intent potential that deserves upfront randomized testing. PROTOCOL NUMBERS: EUDRACT 2007-004632-24, NCT00852228.

Nomogram for prediction of prognosis in patients with initially unresectable colorectal liver metastases.

BACKGROUND: Although recent advances in surgery and chemotherapy have increasingly enabled hepatectomy in patients with initially unresectable colorectal liver metastases (CRLM), not all such patients benefit from surgery. The aim of this study was to develop a nomogram to predict survival after hepatectomy for initially unresectable CRLM. METHODS: Patients with initially unresectable CRLM treated with chemotherapy followed by hepatectomy between 1990 and 2012 were included in the study. A nomogram to predict survival was developed based on a multivariable Cox model. The predictive performance of the model was assessed according to the C-statistic, Kaplan-Meier curve and calibration plots. RESULTS: Of a total of 439 patients, liver and globally completed surgery was achieved in 380 (86·6 per cent) and 335 (76·3 per cent) patients respectively. The 5-year overall and disease-free survival rates were 39·9 and 10·0 per cent respectively. Based on the Cox model, the following five factors were selected for the nomogram and assigned specific scores: node-positive primary, 5; more than six metastases at hepatectomy, 7; carbohydrate antigen 19-9 level at hepatectomy above 37 units/ml, 10; disease progression during first-line chemotherapy, 9; and presence of extrahepatic disease, 4. The model achieved relatively good discrimination and calibration, with a C-statistic of 0·66. The overall survival rate for patients with a score greater than 16 was significantly worse than that for patients with a score of 16 or less (5-year survival rate 4 versus 46·3 per cent respectively; P < 0·001). CONCLUSION: The nomogram facilitates personalized assessment of prognosis for patients with initially unresectable CRLM treated with chemotherapy and with planned resection.

Outcome after associating liver partition and portal vein ligation for staged hepatectomy and conventional two-stage hepatectomy for colorectal liver metastases.

BACKGROUND: Although associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) has been increasingly adopted by many centres, the oncological outcome for colorectal liver metastases compared with that after two-stage hepatectomy is still unknown. METHODS: Between January 2010 and June 2014, all consecutive patients who underwent either ALPPS or two-stage hepatectomy for colorectal liver metastases in a single institution were included in the study. Morbidity, mortality, disease recurrence and survival were compared. RESULTS: The two groups were comparable in terms of clinicopathological characteristics. ALPPS was completed in all 17 patients, whereas the second-stage hepatectomy could not be completed in 15 of 41 patients. Ninety-day mortality rates for ALPPS and two-stage resection were 0 per cent (0 of 17) versus 5 per cent (2 of 41) (P = 0·891). Major complication rates (Clavien grade at least III) were 41 per cent (7 of 17) and 39 per cent (16 of 41) respectively (P = 0·999). Overall survival was significantly lower after ALPPS than after two-stage hepatectomy: 2-year survival 42 versus 77 per cent respectively (P = 0·006). Recurrent disease was more often seen in the liver in the ALPPS group. Salvage surgery was less often performed after ALPPS (2 of 8 patients) than after two-stage hepatectomy (10 of 17). CONCLUSION: Although major complication and 90-day mortality rates of ALPPS were similar to those of two-stage hepatectomy, overall survival was significantly lower following ALPPS.

Compared efficacy of preservation solutions in liver transplantation: a long-term graft outcome study from the European Liver Transplant Registry.

Between 2003 and 2012, 42 869 first liver transplantations performed in Europe with the use of either University of Wisconsin solution (UW; N = 24 562), histidine-tryptophan-ketoglutarate(HTK; N = 8696), Celsior solution (CE; N = 7756) or Institute Georges Lopez preservation solution (IGL-1; N = 1855) preserved grafts. Alternative solutions to the UW were increasingly used during the last decade. Overall, 3-year graft survival was higher with UW, IGL-1 and CE (75%, 75% and 73%, respectively), compared to the HTK (69%) (p < 0.0001). The same trend was observed with a total ischemia time (TIT) >12 h or grafts used for patients with cancer (p < 0.0001). For partial grafts, 3-year graft survival was 89% for IGL-1, 67% for UW, 68% for CE and 64% for HTK (p = 0.009). Multivariate analysis identified HTK as an independent factor of graft loss, with recipient HIV (+), donor age ≥65 years, recipient HCV (+), main disease acute hepatic failure, use of a partial liver graft, recipient age ≥60 years, no identical ABO compatibility, recipient hepatitis B surface antigen (-), TIT ≥ 12 h, male recipient and main disease other than cirrhosis. HTK appears to be an independent risk factor of graft loss. Both UW and IGL-1, and CE to a lesser extent, provides similar results for full size grafts. For partial deceased donor liver grafts, IGL-1 tends to offer the best graft outcome.

Vascular reconstruction combined with liver resection for malignant tumours.

BACKGROUND: The resectability criteria for malignant liver tumours have expanded during the past two decades. The use of vascular reconstruction after hepatectomy has been integral in this process. However, the majority of reports are anecdotal. This is a retrospective analysis of the techniques, morbidity, mortality and risk factors of liver resections with vascular reconstruction based on a large series from a single centre. METHODS: Patients who underwent hepatic resection combined with vascular resection and reconstruction between 1997 and 2009 were included in this study. Indications for surgery, morbidity and 90-day mortality are reported along with factors predictive of operative mortality. RESULTS: Eighty-four patients had liver resection with 97 vascular resections and reconstruction. There were 44 men and 40 women with a mean(s.d.) age of 56·9(12·1) years. Mean(s.d.) follow-up was 37·3(34·1) months. All patients had primary or metastatic liver tumours. The perioperative morbidity rate was 62 per cent (52 patients) and the operative mortality rate 14 per cent (12). Predictors of operative mortality were: bilirubin level exceeding 34 µmol/ml (P = 0·023), indocyanine green retention rate at 15 min over 10 per cent (P = 0·031), duration of ischaemia (P = 0·011), amount of blood transfused (P = 0·025) and combined major extrahepatic procedure (P = 0·042). Actuarial 3- and 5-year survival rates were 44 and 26 per cent respectively. CONCLUSION: Liver resection with combined vascular resection and reconstruction can be performed in selected patients with acceptable morbidity and mortality. The lack of therapeutic alternatives and the poor outcome of non-operative management seem to justify this approach. The identification of risk factors should help improve patient selection and postoperative outcome as well as facilitate objective risk communication with surgical candidates.

Repeat hepatectomy for recurrent colorectal metastases.

BACKGROUND: The oncological benefit of repeat hepatectomy for patients with recurrent colorectal metastases is not yet proven. This study assessed the value of repeat hepatectomy for these patients within current multidisciplinary treatment. METHODS: Consecutive patients treated by repeat hepatectomy for colorectal metastases between January 1990 and January 2010 were included. Patients undergoing two-stage hepatectomy were excluded. Postoperative outcome was analysed and compared with that of patients who had only a single hepatectomy. RESULTS: A total of 1036 patients underwent 1454 hepatectomies for colorectal metastases. Of these, 288 patients had 362 repeat hepatectomies for recurrent metastases. Some 225 patients (78·1 per cent) had two hepatectomies, 52 (18·1 per cent) had three hepatectomies, and 11 patients (3·8 per cent) had a fourth hepatectomy. Postoperative morbidity following repeat hepatectomy was similar to that after initial liver resection (27·1 per cent after first, 34·4 per cent after second and 33·3 per cent after third hepatectomy) (P = 0·069). The postoperative mortality rate was 3·1 per cent after repeat hepatectomy versus 1·6 per cent after first hepatectomy. Three- and 5-year overall survival rates following first hepatectomy in patients who underwent repeat hepatectomy were 76 and 54 per cent respectively, compared with 58 and 45 per cent in patients who had only one hepatectomy (P = 0·003). In multivariable analysis, repeat hepatectomy performed between 2000 and 2010 was the sole independent factor associated with longer overall survival. CONCLUSION: Repeat hepatectomy for recurrent colorectal metastases offers long-term survival in selected patients.

Operative risks of domino liver transplantation for the familial amyloid polyneuropathy liver donor and recipient: a double analysis.

Although domino liver transplantation (LT) is an established procedure, data about the operative risks are limited. This study aimed at evaluating the operative risks of domino LT. Two retrospective analyses were conducted (comparison of familial amyloid polyneuropathy [FAP] liver donors [61 patients] vs. FAP nondonors [39 patients] and FAP liver recipients [61 patients] vs. deceased donor liver recipients [61 patients]). First analysis showed a 60-day mortality of 6.6% for FAP donors and 7.7% for FAP nondonors (p = 1.0). No patient developed primary graft nonfunction. Acute rejection was higher in FAP nondonors compared to FAP donors (38.5% vs. 13.1%). Both groups had similar vascular and biliary complication rates. ICU stay was similar, whereas total hospitalization was longer for FAP nondonors. Both groups had similar 1- and 5-year patient and graft survival rates (83.4% vs. 87.2%, and 79.8% vs. 71.8%, p = 0.7) and (83.3% vs. 87.2%, and 79.1% vs.71.8%, p = 0.7). The second analysis showed a 1.6% mortality for FAP liver recipients vs. 3.2% of the control group (p = 1). Both groups had similar morbidity and technical complication rates (18.0% vs. 13.1%, p = 0.45) and (0.18 vs. 0.15, p = 0.65). The domino procedure does not add any risk to FAP donor or recipient. It increases the organ pool allowing transplantation of marginal recipients who otherwise are denied deceased donor liver transplantation.

Fibrosing cholestatic hepatitis in HIV/HCV co-infected transplant patients-usefulness of early markers after liver transplantation.

We characterized fibrosing cholestatic hepatitis (FCH) in a large cohort of HIV/HCV co-infected patients. Between 1999 and 2008, 59 HIV infected patients were transplanted for end-stage liver disease due to HCV. Eleven patients (19%) developed FCH within a mean period of 7 months [2-27] after liver transplantation (LT). At Week 1 post-LT, the mean HCV viral load was higher in the FCH group: 6.13 log(10) IU/mL ± 1.30 versus 4.9 log(10) IU/mL ± 1.78 in the non-FCH group, p = 0.05. At the onset of acute hepatitis after LT, activity was moderate to severe in 8/11 HIV+/HCV+ patients with FCH (73%) versus 13/28 (46%) HIV+/HCV+ non-FCH (p = 0.007) patients. A complete virological response to anti-HCV therapy was observed in 2/11 (18%) patients. Survival differed significantly between the two groups (at 3 years, 67% in non-FCH patients versus 15% in FCH patients, p = 0.004). An early diagnosis of FCH may be suggested by the presence of marked disease activity when acute hepatitis is diagnosed and when a high viral load is present. The initiation of anti-HCV therapy should be considered at this point.

Short- and long-term donor morbidity in right lobe living donor liver transplantation: 91 consecutive cases in a European Center.

The lack of use of a common grading system in reporting morbidity impedes estimation of the true risk to a right lobe living donor (RLLD). We report outcomes in 91 consecutive RLLD's using the validated 5-tier Clavien grading and a quality of life (QOL) questionnaire. The median follow-up was 79 months. The donors were predominantly female (66%), 22 (24%) received autologous blood transfusions. Fifty-three complications occurred in 43 donors (47% morbidity), 19 (37%) were ≥ Grade III, biliary fistula (14%) was the most common. There was no donor mortality. Two intraoperative complications could not be graded and two disfiguring complications in female donors were graded as minor. Two subgroups (first 46 vs. later 45 donors) were compared to study the presence if any, of a learning curve. The later 45 donors had lesser autologous transfusions, lesser rehospitalization and no reoperation and a reduction in the proportion of ≥ Grade III (major) complications (24% vs. 50%; p = 0.06). In the long term, donors expressed an overall sense of well being, but some sequelae of surgery do restrain their current lifestyle. Our results warn against lackadaisical vigilance once RLLD hepatectomy becomes routine.

Impact of bevacizumab on functional recovery and histology of the liver after resection of colorectal metastases.

BACKGROUND: The impact of bevacizumab on functional recovery and histology of the liver was evaluated in patients undergoing hepatic resection for colorectal liver metastases (CLM) following bevacizumab treatment. METHODS: Consecutive patients who had resection of CLM between July 2005 and July 2009 following preoperative chemotherapy were identified retrospectively from a prospectively collected database. Patients who had received bevacizumab before the last chemotherapy line were excluded. Postoperative liver function and histology were compared between patients with and without bevacizumab treatment. Recorded parameters included serum prothrombin time, total bilirubin concentration, and levels of aspartate and alanine aminotransferase and γ-glutamyltransferase. RESULTS: Of 208 patients identified, 67 had received last-line bevacizumab, 44 were excluded and 97 had not received bevacizumab. Most patients in the bevacizumab group (66 per cent) received a single line of chemotherapy. Bevacizumab was most often combined with 5-flurouracil/leucovorin and irinotecan (68 per cent). The median number of bevacizumab cycles was 8·6 (range 1-34). Bevacizumab administration was stopped a median of 8 (range 3-19) weeks before surgery. There were no deaths. Postoperative morbidity occurred in 43 and 36 per cent of patients in the bevacizumab and no-bevacizumab groups respectively (P = 0·353). The mean(s.d.) degree of tumour necrosis was significantly higher in the bevacizumab group (55(27) versus 32(29) per cent; P = 0·001). Complete pathological response rates were comparable (3 versus 8 per cent; P = 0·307). Postoperative changes in functional parameters and objective signs of hepatic toxicity were similar in both groups. CONCLUSION: Preoperative administration of bevacizumab does not seem to affect functional recovery of the liver after resection of CLM. Tumour necrosis is increased following bevacizumab treatment.

Non-invasive ICG-clearance: a useful tool for the management of hepatic artery thrombosis following liver transplantation.

BACKGROUND: The clinical presentation of hepatic artery thrombosis (HAT) post-liver transplantation (LT) varies considerably. Doppler ultrasonography (Doppler US) is the first line investigation, with a diagnostic sensitivity for HAT as high as 92%. Because indocyanine green (ICG) elimination from the blood depends among other factors on the hepatic blood flow, we hypothesized that plasma disappearance rate of indocyanine green (PDR-ICG) can be influenced by the flow in the hepatic artery. Thus, we evaluated the role of PDR-ICG measurement in HAT diagnosis in post-LT patients. PATIENTS AND METHODS: Fourteen liver transplant patients with no visible flow in the hepatic artery (Doppler US) were identified. Of the 14, seven patients had HAT confirmed by CT-angiography. The PDR-ICG measurement, an investigation routinely used in our center, was performed in all 14 patients. RESULTS: The PDR-ICG in patients with HAT was significantly lower than in patients without HAT (5.8 ± 4.3 vs. 23.8 ± 7.4%/min, p= 0.0009). In patients with HAT, after the revascularization, the PDR-ICG value increased (5.8 ± 4.3 vs. 15.6 ± 3.5%/min, p = 0.006). CONCLUSION: The ICG elimination may be an adjunct diagnostic tool in the management of patients with suspected HAT following LT.

Progression of alphafetoprotein before liver transplantation for hepatocellular carcinoma in cirrhotic patients: a critical factor.

Liver transplantation (LT) for cirrhotic/Hepatocellular carcinoma (HCC) is associated with reduced survival in patients with poor histological features. Preoperative levels of alphafetoprotein (AFP) could predict negative biological features. AFP progression could be more relevant than static AFP levels in predicting LT outcomes. A total of 252 cirrhotic/HCC patients transplanted between 1985 and 2005 were reviewed. One hundred fifty-three patients were analyzed, 99 excluded (for nonsecreting tumors and/or salvage transplantation). Using receiver operating characteristics analysis for recurrence after LT, 'progression' of AFP was defined by >15 microg/L per month before LT. A total of 127 (83%) were transplanted under and 26 (16%) over this threshold. After 45 months of follow-up (median), 5-year overall survival (OS) and recurrence free-survival (RFS) were 72% and 69%, respectively. Five-year survival in the progression group was lower than the nonprogression group (OS 54% vs. 77%; RFS 47% vs. 74%). Multivariate analysis showed progression of AFP>15 microg/L per month and preoperative nodules>3 were associated with decreased OS. Progression group and age>60 years were associated with decreased RFS. Male gender, progression of AFP and size of tumor>30 mm were associated with satellite nodules and/or vascular invasion. In conclusion, increasing AFP>15 microg/L/month while waiting for LT is the most relevant preoperative prognostic factor for low OS/DFS. AFP progression could be a pathological preoperative marker of tumor aggressiveness.

Impact of portal vein embolization on long-term survival of patients with primarily unresectable colorectal liver metastases.

BACKGROUND: : Portal vein embolization (PVE) increases the resectability of initially unresectable colorectal liver metastases (CLM). This study evaluated long-term survival in patients with CLM who underwent hepatectomy following PVE. METHODS: : In a retrospective analysis patients treated by PVE before major hepatectomy were compared with those who did not have PVE, and with those who had PVE without resection. RESULTS: : Of 364 patients who underwent hepatectomy, 67 had PVE beforehand and 297 did not. Those who had PVE more often had more than three liver metastases (68 versus 40.9 per cent; P < 0.001) that were more frequently bilobar (78 versus 55.2 per cent; P < 0.001), and a higher proportion underwent extended hepatectomy (63 versus 18.1 per cent; P < 0.001). Postoperative morbidity rates were 55 and 41.1 per cent respectively (P = 0.035), and overall 3-year survival rates were 44 and 61.0 per cent (P = 0.001). Thirty-two other patients who were treated by PVE but did not undergo resection all died within 3 years. CONCLUSION: : PVE increased the resectability rate of initially unresectable CLM. Among patients who had PVE, long-term survival was better in those who had resection than in those who did not. PVE is of importance in the multimodal treatment of advanced CLM.

Comparison of simultaneous or delayed liver surgery for limited synchronous colorectal metastases.

BACKGROUND: The optimal surgical strategy for patients with synchronous colorectal liver metastases (CLMs) is still unclear. The aim of this study was to compare simultaneous colorectal and hepatic resection with a delayed strategy in patients who had a limited hepatectomy (fewer than three segments). METHODS: All patients with synchronous CLMs who underwent limited hepatectomy between 1990 and 2006 were included retrospectively. Short-term outcome, overall and progression-free survival were compared in patients having simultaneous colorectal and hepatic resection and those treated by delayed hepatectomy. RESULTS: Of 228 patients undergoing hepatectomy for synchronous CLMs, 55 (24.1 per cent) had a simultaneous colorectal resection and 173 (75.9 per cent) had delayed hepatectomy. The mortality rate following hepatectomy was similar in the two groups (0 versus 0.6 per cent respectively; P = 0.557), but cumulative morbidity was significantly lower in the simultaneous group (11 per cent versus 25.4 per cent in the delayed group; P = 0.015). Three-year overall and progression-free survival rates were 74 and 8 per cent respectively in the simultaneous group, compared with 70.3 and 26.1 per cent in the delayed group (overall survival: P = 0.871; progression-free survival: P = 0.005). Significantly more recurrences were observed in the simultaneous group at 3 years (85 versus 63.6 per cent; P = 0.002); a simultaneous strategy was an independent predictor of recurrence. CONCLUSION: Combining colorectal resection with a limited hepatectomy is safe in patients with synchronous CLMs and associated with less cumulative morbidity than a delayed procedure. However, the combined strategy has a negative impact on progression-free survival.

Extended measures for controlling an outbreak of VIM-1 producing imipenem-resistant Klebsiella pneumoniae in a liver transplant centre in France, 2003-2004.

We report the successful control of an outbreak caused by imipenem-resistant VIM-1-producing Klebsiella pneumoniae (IR-Kp) in France. This outbreak occurred in a care centre for abdominal surgery that includes a 15-bed liver intensive care unit and performs more than 130 liver transplantations per year. The index case was a patient with acute liver failure transferred from a hospital in Greece for urgent liver transplantation who was carrying IR-Kp at admission as revealed by routine culture of a rectal swab. Infection control measures were undertaken and included contact isolation and promotion of hand hygiene with alcohol-based hand rub solution. Nevertheless, secondary IR-Kp cases were identified during the six following months from 3 December 2003 to 2 June 2004. From 2 June to 21 October, extended infection control measures were set up, such as cohorting IR-Kp carriers, contact patients and new patients in distinct sections with dedicated staff, limiting ward admission, and strict control of patient transfer. They led to a rapid control of the outbreak. The global attack rate of the IR-Kp outbreak was 2.5%, 13% in liver transplant patients and 0.4% in the other patients in the care centre (p<0.005). Systematic screening for IR-Kp of all patients admitted to the care centre is still maintained to date and no secondary IR-Kp case has been detected since 2 June 2004.