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.

Multicentre study of the impact of morbidity on long-term survival following hepatectomy for intrahepatic cholangiocarcinoma.

BACKGROUND: The impact of morbidity on long-term outcomes following liver resection for intrahepatic cholangiocarcinoma is currently unclear. METHODS: This was a retrospective analysis of all consecutive patients who underwent liver resection for intrahepatic cholangiocarcinoma with curative intent in 24 university hospitals between 1989 and 2009. Severe morbidity was defined as any complication of Dindo-Clavien grade III or IV. Patients with severe morbidity were compared with those without in terms of demographics, pathology, management, morbidity, overall survival, disease-free survival and time to recurrence. Independent predictors of severe morbidity were identified by multivariable analysis. RESULTS: A total of 522 patients were enrolled. Severe morbidity occurred in 113 patients (21·6 per cent) and was an independent predictor of overall survival (hazard ratio 1·64, 95 per cent c.i. 1·21 to 2·23), as were age at resection, multifocal disease, positive lymph node status and R0 resection margin. Severe morbidity did not emerge as an independent predictor of disease-free survival. Independent predictors of time to recurrence included severe morbidity, tumour size, multifocal disease, vascular invasion and R0 resection margin. Major hepatectomy and intraoperative transfusion were independent predictors of severe morbidity. CONCLUSION: Severe morbidity adversely affects overall survival following liver resection for intrahepatic cholangiocarcinoma.

Factors influencing recurrence following initial hepatectomy for colorectal liver metastases.

BACKGROUND: Data on recurrence patterns following hepatectomy for colorectal liver metastases (CRLMs) and their impact on long-term outcomes are limited in the setting of modern multimodal management. This study sought to characterize the patterns of, factors associated with, and survival impact of recurrence following initial hepatectomy for CRLMs. METHODS: A retrospective cohort study of patients undergoing initial hepatectomy for CRLMs at 39 institutions (2006-2013) was conducted. Kaplan-Meier methods were used for survival analyses. Overall survival landmark analysis at 12 months after hepatectomy was performed to compare groups based on recurrence. Multivariable Cox and regression models were used to determine factors associated with recurrence. RESULTS: Among 2320 patients, tumours recurred in 47·4 per cent at median of 10·1 (range 0-88) months; 89·1 per cent of recurrences developed within 3 years. Recurrence was intrahepatic in 46·2 per cent, extrahepatic in 31·8 per cent and combined intra/extrahepatic in 22·0 per cent. The 5-year overall survival rate decreased from 74·3 (95 per cent c.i. 72·2 to 76·4) per cent without recurrence to 57·5 (55·0 to 60·0) per cent with recurrence (adjusted hazard ratio (HR) 3·08, 95 per cent c.i. 2·31 to 4·09). After adjusting for clinicopathological variables, prehepatectomy factors associated with increased risk of recurrence were node-positive primary tumour (HR 1·27, 1·09 to 1·49), more than three liver metastases (HR 1·27, 1·06 to 1·52) and largest metastasis greater than 4 cm (HR 1·19; 1·01 to 1·43). CONCLUSION: Recurrence after CRLM resection remains common. Although overall survival is inferior with recurrence, excellent survival rates can still be achieved.

Administration of low doses of IL-2 combined to rapamycin promotes allogeneic skin graft survival in mice.

Human CD4(+) CD25(+) FoxP3(+) regulatory T cells (Tregs) prevent allogeneic graft rejection by inhibiting T cell activation, as has been shown in mouse models. Recently, low-dose IL-2 administration was shown to specifically activate Tregs but not pathogenic conventional T cells, leading to resolution of type 1 diabetes in nonobese diabetic mice. We therefore tested the ability of low-dose IL-2 to prevent allogeneic skin graft rejection. We found that while IL-2 alone was inefficient in preventing rejection, combined with rapamycin, IL-2 treatment promoted skin graft survival both in minor disparate and semi-allogeneic skin graft combinations. Tregs are activated by this combined treatment while conventional CD4(+) cell expansion and activation are markedly inhibited. Co-administration of anti-CD25 antibodies dramatically reduces the effect of the IL-2/rapamycin treatment, strongly supporting a central role for Treg activation. Thus, we provide the first preclinical data showing that low-dose IL-2 combined with rapamycin can significantly delay transplant rejection in mice. These findings may form the rational for clinical evaluation of this novel approach for the prevention of transplant rejection.

Candida vascular complication in a liver transplant recipient due to yeast contamination of preservation solution.

Infections remain a major cause of morbidity and mortality after liver transplantation. One possible cause of infection is preservation fluid contamination. Donor-derived pathogens, such as Candida albicans, have occasionally produced life-threatening complications in organ recipients, already described in renal transplantation. In the present case, we report the loss of a liver graft secondary to vascular complications because of C. albicans found in the preservation fluid. Our case report raises the question of implementing procedures, similar to those in renal transplantation, including early antifungal treatment and repeated radiological monitoring for the prevention and detection of vascular complications.

NOTES total mesorectal excision (TME) for patients with rectal neoplasia: a preliminary experience.

BACKGROUND: Natural orifice transluminal endoscopic surgery (NOTES) and single-incision laparoscopy are emerging, minimally invasive techniques. Total mesorectal excision (TME), the gold standard treatment for patients with resectable distal rectal tumors, is usually performed in an "up-to-down" approach, either laparoscopically or via open techniques. A transanal, "down-to-up" TME has already been reported. Our NOTES variant of TME (NOTESTME) is based on a transperineal approach without any form of abdominal assistance. The aim was to reduce further the invasiveness of the procedure while optimizing the anatomical definition of the distal mesorectum. This approach may lead to reduced postoperative pain, decreased hernia formation and improved cosmesis when compared to standard laparoscopy. METHODS: NOTESTME was attempted in 16 patients with distal rectal neoplasia (i.e., distal edge of the tumor lower than the pouch of Douglas, between 0 and 12 cm from the dentate line). Additional inclusion criteria consisted of an ASA status ≤III and the absence of previous abdominal surgery. RESULTS: NOTESTME was completed in all patients. Additional abdominal, single-incision laparoscopic assistance was required in 6 (38 %) patients. Mean operative time was 265 min (range 155-440 min). The morbidity rate was 18.8 % (two small bowel obstructions and one pelvic abscess), requiring re-operation in each case. No leaks occurred, and the mortality rate at 30 and 90 days was 0 %. Resection margins were negative in all patients. A median of 17 nodes (range 12-81) was retrieved per specimen. Mean length of hospital stay was 10 days (range 4-29 days). Patients were followed for an average of 7 months (range 3-23 months). CONCLUSION: NOTESTME was feasible and safe in this series of patients with mid- or low rectal tumors. The short-term mortality and morbidity rates are acceptable, with no apparent compromise in the oncological quality of the resection. Larger, randomized controlled trials with long-term follow-up are warranted.

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.

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.

Long-term outcome in patients with adrenal metastases following resection of colorectal liver metastases.

BACKGROUND: The prognostic significance of adrenal metastases (AMs) in patients with colorectal liver metastases (CLMs) remains unknown. The aim of this study was to determine the influence of AMs on long-term outcome and the role of adrenalectomy in patients with CLMs. METHODS: All patients resected for CLMs who developed AMs at a single institution between 1992 and 2006 were included in the study. Their long-term outcome was compared with that of all other patients resected for CLMs but without AMs. RESULTS: Hepatectomy was performed in 796 patients, of whom 14 (1.8 per cent) developed AMs, a median of 28 months after initial diagnosis of CLMs; the remaining 782 patients (98.2 per cent) had no AMs. All 14 patients had chemotherapy, and ten went on to adrenalectomy. Median survival after diagnosis of CLMs was 50 months in patients with AMs versus 68 months in those without (P = 0.020). After diagnosis of AMs, median survival was 23 months, whether or not adrenalectomy was performed. CONCLUSION: The development of AMs after liver resection for colorectal cancer deposits carries a poor prognosis, and adrenalectomy is probably not warranted.

Fibromyalgia in the workplace: risk factors for sick leave are related to professional context rather than fibromyalgia characteristics- a French national survey of 955 patients.

BACKGROUND: Work and workplace factors are important in fibromyalgia management. We investigated factors associated with sick leave in professionally active women living with fibromyalgia. METHODS: A questionnaire for fibromyalgia patients in employment was developed by pain and occupational physicians and patients' organizations. Women in full-time work, screened for fibromyalgia with the FiRST questionnaire, were recruited for a national online survey. Sick leave over the preceding year was analyzed. RESULTS: In 5 months, we recruited 955 women, with a mean of 37 days of sick leave in the previous year: no sick leave (36%), up to 1 month (38%), 1 to 2 months (14%), more than 2 months (12%). In the groups displayed no differences in demographic characteristics, fibromyalgia symptoms, functional severity and psychological distress were observed. However, they differed in workplace characteristics, commute time, stress and difficulties at work, repetitive work, noisy conditions, career progression problems and lack of recognition, which were strong independent risk factors for longer sick leave. Sedentary positions, an extended sitting position, heavy loads, exposure to thermal disturbances and the use of vibrating tools did not increase the risk of sick leave. CONCLUSIONS: Women with fibromyalgia frequently take sick leave, the risk factors for which are related to the workplace rather than fibromyalgia characteristics. PERSPECTIVE: This is the first study to assess the impact of occupational and clinical factors on sick leave in women living with fibromyalgia. Risk factors were found to be related to the workplace rather than fibromyalgia and personal characteristics. Workplace interventions should be developed for women with fibromyalgia.

Bevacizumab improves survival in patients with synchronous colorectal liver metastases provided the primary tumor is resected first.

BACKGROUND: Multimodal strategy including chemotherapy and hepatectomy is advocated for the management of colorectal liver metastases (CRLM). The aim of this study was to evaluate the impact of neoadjuvant Bevacizumab-based chemotherapy on survival in patients with resected stage IVA colorectal cancer and liver metastases. METHODS: Data from 120 consecutive patients who received neoadjuvant chemotherapy and underwent curative-intent hepatectomy for synchronous CRLM were retrospectively reviewed. Overall survival (OS) was stratified according to administration of Bevacizumab before liver resection and surgical strategy, i.e., classical strategy (primary tumor resection first) versus reverse strategy (liver metastases resection first). RESULTS: Patients who received Bevacizumab (n = 37; 30%) had a higher number of CRLM (p = 0.003) and underwent more often reverse strategy (p = 0.005), as compared to those who did not (n = 83; 70%). Bevacizumab was associated with an improved OS compared with conventional chemotherapy (p = 0.04). After stratifying by the surgical strategy, Bevacizumab was associated with improved OS in patients who had classical strategy (p = 0.03). In contrast, Bevacizumab had no impact on OS among patients who had liver metastases resection first (p = 0.89). CONCLUSIONS: Neoadjuvant Bevacizumab-based chemotherapy was associated with improved OS in patients who underwent liver resection of synchronous CRLM, especially in those who underwent primary tumor resection first.

Hepatic Iron Overload following Liver Transplantation from a C282Y/H63D Compound Heterozygous Donor.

Hereditary hemochromatosis (HH) is a genetic disease associated with progressive iron overload, eventually leading in some cases to damage of parenchymal organs, such as the liver, pancreas, and heart. Although the gene had been identified (HFE), HH pathogenesis remains to be fully elucidated. We report here, for the first time, a case of inadvertent transplantation of a liver from a donor with C282Y/H63D compound heterozygosity into a nonhemochromatotic 19-year-old Caucasian male recipient with primary sclerosing cholangitis. Progressive iron overload occurred over 1.5 years, as observed in liver biopsies and iron studies, after ruling out secondary causes of iron overload. This case strengthens the hypothesis that the liver, rather than the small intestine, plays a primary role in the maintenance of iron homeostasis.

A better definition of the anti-DFS70 antibody screening by IIF methods.

BACKGROUND: Anti-DFS70 antibodies have been recently included in a new testing algorithm for patients with suspicion of connective tissue diseases (CTDs). This algorithm enables to assess the probability of having a CTD in patients with a positive antinuclear antibodies (ANA) result. The aim of the study was to analyze the the inter-method agreement between three different HEp-2 cell substrates for anti-DFS70 detection, focusing on two novel IIF methods that assess the presence of monospecific anti-DFS70 antibodies. METHODS: Immunological and clinical records of 29 patients who were double positive for anti-DFS70 autoantibodies using chemiluminescence assay (CIA) and Immunoblot (IB) were studied. The IIF on HEp-2 cells were determined using slides from Inova Diagnostics, Euroimmun and Immco. The capability to detect isolated anti-DFS70 antibodies was compared using immunoadsorption on NOVA Lite HEp-2 Select (Inova Diagnostics) and the HEp-2 ELITE/DFS70 knockout test (Immco). RESULTS: The three substrates had very good sensitivity for detecting patients with anti-DFS staining pattern (93.1%, 79.3% and 72.4% for Euroimmun, Immco and Inova respectively). Most of the patients had full inhibition of DFS pattern (65.5%) by immunoabsorption test. Also, the 55.2% of the subjects were positive for monospecific DFS pattern using HEp-2 ELITE/DFS70 knockout test. However, the correlation between the full inhibition by immunoadsorption and the monospecific DFS pattern in knockout cells was very low (kappa: 0.22). CONCLUSION: The evaluation of monospecific anti-DFS70 antibodies is clinically fundamental and challenging using traditional HEp-2 IIF. Results obtained in this study support the hypothesis that the lack of standardization across IIF kits along with the subjectivity of user interpretation among other factors contribute to the overall reduction in the agreement.