| 1. |
- Biglarnia, Ali-Reza, et al.
(författare)
-
Liver regeneration is impaired by FK778 in partially hepatectomized rats, while supplemental uridine restores both liver growth and hepatocyte proliferation
- 2009
-
Ingår i: Hepatology Research. - 1386-6346 .- 1872-034X. ; 39:1, s. 86-92
-
Tidskriftsartikel (refereegranskat)abstract
- Aim:The impact of mandatory immunosuppression on liver regeneration after segmental liver transplantation is of clinical importance. FK778, a novel immunosuppressant, inhibits pyrimidine biosynthesis and prevents rejection after organ transplantation in a dose-dependent manner. We investigated the effect of FK778 at a highly effective dose on liver regeneration in a small animal model.Methods: Inbred Lewis rats were subjected to 70% partial hepatectomy (PH) and treated with saline (n = 28), uridine (n = 16), FK778 alone (n = 28) or in combination with uridine (n = 16). FK778 was given intravenously daily at a dose of 25 mg/kg bodyweight (bw) and uridine was given daily intraperitoneally at a dose of 250 mg/kg bw. Liver bodyweight ratio (LBR), hepatocyte proliferation index (PI), blood chemistry and morphological analysis were incorporated. PI was determined by Ki-67 immunostaining. De Ritis ratio was calculated to assess the extent of liver damage.Results:In FK778-treated animals PI was decreased at 24 h and 72 h and LBR was lower at 48 h and 72 h (P < 0.05) after the PH. In addition, morphological analysis showed confluent central lobular necrosis at 72 h in four of seven animals. Uridine supplementation restored PI, LBR and the de Ritis ratio in FK778-treated animals and no confluent necroses were observed.Conclusion:FK778 is antihepatotrophic as well as antiproliferative during rat liver regeneration. Both liver growth and hepatocyte proliferation are completely restored by supplementation with uridine. In addition, supplemental uridine markedly reduces the severity of morphological abnormalities consistent with FK778 toxicity.
|
|
| 2. |
- Bureau, Christophe, et al.
(författare)
-
Alfapump® system vs. large volume paracentesis for refractory ascites : a multicenter randomized controlled study
- 2017
-
Ingår i: Journal of Hepatology. - : Elsevier. - 0168-8278 .- 1600-0641. ; 67:5, s. 940-949
-
Tidskriftsartikel (refereegranskat)abstract
- Background and aims: Patients with refractory ascites (RA) require repeated large volume paracenteses (LVP), which involves frequent hospital visits and is associated with a poor quality-of-life. This study assessed safety and efficacy of an automated, low-flow pump (alfapump® [AP]) compared with LVP standard of care [SoC].Methods: A randomized controlled trial, in seven centers, with six month patient observation was conducted. Primary outcome was time to first LVP. Secondary outcomes included paracentesis requirement, safety, health-related quality-of-life (HRQoL), and survival. Nutrition, hemodynamics, and renal injury biomarkers were assessed in a sub-study at three months.Results: Sixty patients were randomized and 58 were analyzed (27 AP, 31 SoC, mean age 61.9years, mean MELD 11.7). Eighteen patients were included in the sub-study. Compared with SoC, median time to first LVP was not reached after six months in the AP group, meaning a significant reduction in LVP requirement for the AP patients (AP, median not reached; SoC, 15.0days (HR 0.13; 95%CI 13.0-22.0; p<0.001), and AP patients also showed significantly improved Chronic Liver Disease Questionnaire (CLDQ) scores compared with SoC patients (p<0.05 between treatment arms). Improvements in nutritional parameters were observed for hand-grip strength (p=0.044) and body mass index (p<0.001) in the sub-study. Compared with SoC, more AP patients reported adverse events (AEs; 96.3% vs. 77.4%, p=0.057) and serious AEs (85.2 vs. 45.2%, p=0.002). AEs consisted predominantly of acute kidney injury in the immediate post-operative period, and re-intervention for pump related issues, and were treatable in most cases. Survival was similar in AP and SoC.Conclusions: The AP system is effective for reducing the need for paracentesis and improving quality of life in cirrhotic patients with RA. Although the frequency of SAEs (and by inference hospitalizations) was significantly higher in the AP group, they were generally limited and did not impact survival.Lay summary: The alfapump® moves abdominal fluid into the bladder from where it is then removed by urination. Compared with standard treatment, the alfapump reduces the need for large volume paracentesis (manual fluid removal by needle) in patients with medically untreatable ascites. This can improve life quality for these patients.
|
|
| 3. |
- Enne, Marcelo, et al.
(författare)
-
ALPPS as a salvage procedure after insufficient future liver remnant hypertrophy following portal vein occlusion
- 2017
-
Ingår i: HPB. - : ELSEVIER SCI LTD. - 1365-182X .- 1477-2574. ; 19:12, s. 1126-1129
-
Tidskriftsartikel (refereegranskat)abstract
- Background: A minimum future liver remnant (FLR) of 30% is required to avoid post hepatectomy liver failure (PHLF). Portal vein occlusion (PVO) is the main strategy to induce hypertrophy of the FLR, but some patients will not reach sufficient FLR hypertrophy to enable resection. Recently ALPPS has emerged as a "Salvage Procedure" for PVO failure. The aim of this study was to report the short term outcomes of ALPPS following PVO failure. Methods: A retrospective analysis of patients enrolled within the international ALPPS Registry between October 2012 and November 2015 (NCT01924741) was performed. Patients with documented PVO failure were included. The outcomes reported included feasibility, FLR growth rate and safety of ALPPS. Complications were recorded as per Clavien-Dindo classification. Results: From 510 patients enrolled in the Registry there were 22 patients with previous PVO failure. Two patients were excluded due to missing data and twenty patients were analysed. All of them completed the proposed ALPPS with a medium FLR increase of 88% (23-115%) between two stages and no 90-day mortality. Conclusion: In experienced centers, ALPPS following PVO failure is feasible and safe. The FLR hypertrophy was similar to other ALPPS series. ALPPS is a potential rescue strategy after PVO failure.
|
|
| 4. |
- Hasselgren, Kristina, et al.
(författare)
-
Neoadjuvant chemotherapy does not affect future liver remnant growth and outcomes of associating liver partition and portal vein ligation for staged hepatectomy
- 2017
-
Ingår i: Surgery. - : MOSBY-ELSEVIER. - 0039-6060 .- 1532-7361. ; 161:5, s. 1255-1265
-
Tidskriftsartikel (refereegranskat)abstract
- Background. The only potentially curative treatment for patients with colorectal liver metastases is hepatectomy. Associating liver partition and portal vein ligation for staged hepatectomy has emerged as a method of treatment for patients with inadequate future liver remnant. One concern about associating liver partition and portal vein ligation for staged hepatectomy is that preoperative chemotherapy may negatively affect the volume increase of the future liver remnant and outcomes. Methods. This study from the International Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy Registry (NCT01924741) includes 442 patients with colorectal liver metastases registered from 2012-2016. Future liver remnant hypertrophy (absolute increase, percent increase, and kinetic growth rate) and clinical outcome were analyzed retrospectively in relation to type and amount of chemotherapy. The analyzed groups included patients with no chemotherapy, 1 regimen of chemotherapy, amp;gt; 1 regimen, and a group that received monoclonal antibodies in addition to chemotherapy. Results. Ninety percent of the patients received neoadjuvant oncologic therapy including 42% with 1 regimen of chemotherapy, 44% with monoclonal antibodies, and 4% with amp;gt; 1 regimen. Future liver remnant increased between 74-92% with the largest increase in the group with 1 regimen of chemotherapy. The increase in milliliters was between 241 mL (amp;gt; 1 regimen) and 306 mL (1 regimen). Kinetic growth rate was between 14-18% per week and was greatest for the group with 1 regimen of chemotherapy. No statistical significance was found between the groups with any of the measurements of future liver remnant hypertrophy. Conclusion. Neoadjuvant chemotherapy, including monoclonal antibodies, does not negatively affect future liver remnant growth. Patients with colorectal liver metastases who might be potential candidates for associating liver partition and portal vein ligation for staged hepatectomy should be considered for neoadjuvant chemotherapy. (Surgery 2017;161:1255-65.)
|
|
| 5. |
- Lang, Hauke, et al.
(författare)
-
10th Anniversary of ALPPS-Lessons Learned and quo Vadis
- 2019
-
Ingår i: Annals of Surgery. - : LIPPINCOTT WILLIAMS & WILKINS. - 0003-4932 .- 1528-1140. ; 269:1, s. 114-119
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: Associating Liver Partition and Portal vein ligation for Staged hepatectomy (ALPPS) has been tested in various indications and clinical scenarios, leading to steady improvements in safety. This report presents the current status of ALPPS. Summary Background Data: ALPPS offers improved resectability, but drawbacks are regularly pointed out regarding safety and oncologic benefits. Methods: During the 12th biennial congress of the European African-Hepato-Pancreato-Biliary Association (Mainz, Germany, May 23-26, 2017) an expert meeting "10th anniversary of ALPP" was held to discuss indications, management, mechanisms of regeneration, as well as pitfalls of this novel technique. The aim of the meeting was to make an inventory of what has been achieved and what remains unclear in ALPPS. Results: Precise knowledge of liver anatomy and its variations is paramount for success in ALPPS. Technical modifications, mainly less invasive approaches like partial, mini- or laparoscopic ALPPS, mostly aiming at minimizing the extensiveness of the first-stage procedure, are associated with improved safety. In fibrotic/cirrhotic livers the degree of future liver remnant hypertrophy after ALPPS appears some less than that in noncirrhotic. Recent data from the only prospective randomized controlled trial confirmed significant higher resection rates in ALPPS with similar peri-operative morbidity and mortality rates compared with conventional 2-stage hepatectomy including portal vein embolization. ALPPS is effective reliably even after failure of portal vein embolization. Conclusions: Although ALPPS is now an established 2-stage hepatectomy additional data are warranted to further refine indication and technical aspects. Long-term oncological outcome results are needed to establish the place of ALPPS in patients with initially nonresectable liver tumors.
|
|
| 6. |
- Li, Jun, et al.
(författare)
-
ALPPS for Locally Advanced Intrahepatic Cholangiocarcinoma: Did Aggressive Surgery Lead to the Oncological Benefit? An International Multi-center Study
- 2020
-
Ingår i: Annals of Surgical Oncology. - : SPRINGER. - 1068-9265 .- 1534-4681. ; 27, s. 1372-1384
-
Tidskriftsartikel (refereegranskat)abstract
- Background ALPPS is found to increase the resectability of primary and secondary liver malignancy at the advanced stage. The aim of the study was to verify the surgical and oncological outcome of ALPPS for intrahepatic cholangiocarcinoma (ICC). Methods The study cohort was based on the ALPPS registry with patients from 31 international centers between August 2009 and January 2018. Propensity score matched patients receiving chemotherapy only were selected from the SEER database as controls for the survival analysis. Results One hundred and two patients undergoing ALPPS were recruited, 99 completed the second stage with median inter-stage duration of 11 days. The median kinetic growth rate was 23 ml/day. R0 resection was achieved in 87 (85%). Initially high rates of morbidity and mortality decreased steadily to a 29% severe complication rate and 7% 90-day morbidity in the last 2 years. Post-hepatectomy liver failure remained the main cause of 90-day mortality. Multivariate analysis revealed insufficient future liver remnant at the stage-2 operation (FLR2) to be the only risk factor for severe complications (OR 2.91, p = 0.02). The propensity score matching analysis showed a superior overall survival in the ALPPS group compared to palliative chemotherapy (median overall survival: 26.4 months vs 14 months; 1-, 2-, and 3-year survival rates: 82.4%, 70.5% and 39.6% vs 51.2%, 21.4% and 11.3%, respectively, p amp;lt; 0.01). The survival benefit, however, was not confirmed in the subgroup analysis for patients with insufficient FLR2 or multifocal ICC. Conclusion ALPPS showed high efficacy in achieving R0 resections in locally advanced ICC. To get the most oncological benefit from this aggressive surgery, ALPPS would be restricted to patients with single lesions and sufficient FLR2.
|
|
| 7. |
- Linecker, Michael, et al.
(författare)
-
Risk Adjustment in ALPPS Is Associated With a Dramatic Decrease in Early Mortality and Morbidity
- 2017
-
Ingår i: Annals of Surgery. - : LIPPINCOTT WILLIAMS & WILKINS. - 0003-4932 .- 1528-1140. ; 266:5, s. 779-786
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: To longitudinally assess whether risk adjustment in Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy (ALPPS) occurred over time and is associated with postoperative outcome. Background: ALPPS is a novel 2-stage hepatectomy enabling resection of extensive hepatic tumors. ALPPS has been criticized for its high mortality, which is reported beyond accepted standards in liver surgery. Therefore, adjustments in patient selection and technique have been performed but have not yet been studied over time in relation to outcome. Methods: ALPPS centers of the International ALPPS Registry having performed amp;gt;= 10 cases over a period of amp;gt;= 3 years were assessed for 90-day mortality and major interstage complications (amp;gt;= 3b) of the longitudinal study period from 2009 to 2015. The predicted prestage 1 and 2 mortality risks were calculated for each patient. In addition, questionnaires were sent to all centers exploring center-specific risk adjustment strategies. Results: Among 437 patients from 16 centers, a shift in indications toward colorectal liver metastases from 53% to 77% and a reverse trend in biliary tumors from 24% to 9% were observed. Over time, 90-day mortality decreased from initially 17% to 4% in 2015 (P = 0.002). Similarly, major interstage complications decreased from 10% to 3% (P = 0.011). The reduction of 90-day mortality was independently associated with a risk adjustment in patient selection (P amp;lt; 0.001; OR: 1.62; 95% CI: 1.36-1.93) and using less invasive techniques in stage-1 surgery (P = 0.019; OR: 0.39; 95% CI: 0.18-0.86). A survey indicated risk adjustment of patient selection in all centers and ALPPS technique in the majority (80%) of centers. Conclusions: Risk adjustment of patient selection and technique in ALPPS resulted in a continuous drop of early mortality and major postoperative morbidity, which has meanwhile reached standard outcome measures accepted for major liver surgery.
|
|
| 8. |
- Lopez-Lopez, Victor, et al.
(författare)
-
Liver growth prediction in ALPPS - A multicenter analysis from the international ALPPS registry
- 2022
-
Ingår i: Liver international (Print). - : WILEY. - 1478-3223 .- 1478-3231. ; 42:12, s. 2815-2829
-
Tidskriftsartikel (refereegranskat)abstract
- BackgroundWhile ALPPS triggers a fast liver hypertrophy, it is still unclear which factors matter most to achieve accelerated hypertrophy within a short period of time. The aim of the study was to identify patient-intrinsic factors related to the growth of the future liver remnant (FLR).MethodsThis cohort study is composed of data derived from the International ALPPS Registry from November 2011 and October 2018. We analyse the influence of demographic, tumour type and perioperative data on the growth of the FLR. The volume of the FLR was calculated in millilitre and percentage using computed-tomography (CT) scans before and after stage 1, both according to Vauthey formula.ResultsA total of 734 patients were included from 99 centres. The median sFLR at stage 1 and stage 2 was 0.23 (IQR, 0.18–0.28) and 0.39 (IQR: 0.31–0.46), respectively. The variables associated with a lower increase from sFLR1 to sFLR2 were age˃68 years (p = .02), height ˃1.76 m (p ˂ .01), weight ˃83 kg (p ˂ .01), BMI˃28 (p ˂ .01), male gender (p ˂ .01), antihypertensive therapy (p ˂ .01), operation time ˃370 minutes (p ˂ .01) and hospital stay˃14 days (p ˂ .01). The time required to reach sufficient volume for stage 2, male gender accounts 40.3% in group ˂7 days, compared with 50% of female, and female present 15.3% in group ˃14 days compared with 20.6% of male.ConclusionsHeight, weight, FLR size and gender could be the variables that most constantly influence both daily growths, the interstage increase and the standardized FLR before the second stage.
|
|
| 9. |
- Malago, Massimo, et al.
(författare)
-
Hepatic venous outflow reconstruction in right live donor liver transplantation.
- 2005
-
Ingår i: Liver transplantation. - : Ovid Technologies (Wolters Kluwer Health). - 1527-6465 .- 1527-6473. ; 11:3, s. 364-5
-
Tidskriftsartikel (refereegranskat)abstract
- The increasing experience with live donor liver transplantation has allowed for the identification of potential morbidities associated with technical considerations. Technical graft failure can be associated with both inflow and outflow vascular compromise. Although the latter has not always been given the relevance of the former, evidence pointing to its pivotal role continues to mount. We believe that impaired venous outflow was a cause of previously unexplained graft failures during our initial experience. Based on this observation, we developed a technique to prevent the "choking" of the graft at the outflow anastomosis with the inferior vena cava (IVC). The enhanced outflow via a cloaca maximum is achieved by reconstructing the graft vessels with preserved veins or arteries (usually iliac vessels are used) from a blood-group-identical or blood-group-compatible deceased organ donor. Alternatively, hepatic vein or portal vein obtained from the resected native liver can be used. The reconstructed common outflow is anastomosed to a triangular opening of the IVC. Such enhanced outflow provides optimal venous drainage, especially during the early phase of growth of the graft.
|
|
| 10. |
- Mantini, Cesare, et al.
(författare)
-
Influence of image reconstruction parameters on cardiovascular risk reclassification by Computed Tomography Coronary Artery Calcium Score
- 2018
-
Ingår i: European Journal of Radiology. - : Elsevier BV. - 0720-048X. ; 101, s. 1-7
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: To investigate the influence of different CT reconstruction parameters on coronary artery calcium scoring (CACS) values and reclassification of predicted cardiovascular (CV) risk. Methods: CACS was evaluated in 113 patients undergoing ECG-gated 64-slice CT. Reference CACS protocol included standard kernel filter (B35f) with slice thickness/increment of 3/1.5 mm, and field-of-view (FOV) of 150–180 mm. Influence of different image reconstruction algorithms (reconstructed slice thickness/increment 2.0/1.0–1.5/0.8–3.0/2.0–3.0/3.0 mm; slice kernel B30f-B45f; FOV 200–250 mm) on Agatston score was assessed by Bland-Altman plots and concordance correlation coefficient (CCC) analysis. Classification of CV risk was based on the Mayo Clinic classification. Results: Different CACS reconstruction parameters showed overall good accuracy and precision when compared with reference protocol. Protocols with larger FOV, thinner slices and sharper kernels were associated with significant CV risk reclassification. Use of kernel B45f showed a moderate positive correlation with reference CACS protocol (Agatston CCC = 0.67), and yielded significantly higher CACS values (p <.05). Reconstruction parameters using B30f or B45f kernels, 250 mm FOV, or slice thickness/increment of 2.0/1.0 mm or 1.5/0.8 mm, were associated with significant reclassification of CV risk (p <.05). Conclusions: Kernel, FOV, slice thickness and increment are major determinants of accuracy and precision of CACS measurement. Despite high agreement and overall good correlation of different reconstruction protocols, thinner slices thickness and increment, and sharper kernels were associated with significant upward reclassification of CV risk. Larger FOV determined both upward and downward reclassification of CV risk.
|
|
| 11. |
- Nadalin, Silvio, et al.
(författare)
-
Role and significance of plasma citrulline in the early phase after small bowel transplantation in pigs
- 2007
-
Ingår i: Transplant International. - : Frontiers Media SA. - 0934-0874 .- 1432-2277. ; 20:5, s. 425-431
-
Tidskriftsartikel (refereegranskat)abstract
- A reliable serological marker of acute cellular rejection (ACR) after small bowel transplantation (SBTx) is still missing. Plasma citrulline level (PCL) reflects the functional integrity of intestinal mucosa which is partially lost during ACR. The aim of our study was to investigate the role of PCL as marker of ACR after SBTx. Eighteen German landrace pigs were used and divided into three groups. Group 1 (G1), autologous SBTx (n = 4) as control; group 2 (G2), allogeneic SBTx without immunosuppression (IS) (n = 7) and group 3 (G3), allogeneic SBTx with IS (n = 7). IS consisted of tacrolimus and steroids without induction treatment. Observation period was 14 days. Mucosal biopsies were obtained intraoperatively and daily using a Thiry-Vella loop. ACR was differentiated into indeterminate, mild, moderate and severe using a standardized grading schema. PCL was measured daily. An ACR onset occurred generally from postoperative day 4 both in G2 and G3 as mild form and developed differently in the two groups: moderate to severe in G2 and indeterminate to mild in G3. A significant decline of PCL occurred only in cases of moderate and severe ACR, but not in cases of indeterminate and mild ACR. The PCL failed as a marker in the early diagnosis of ACR and became reliable only when advanced mucosal damage was present.
|
|
