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1.
EClinicalMedicine ; 72: 102608, 2024 Jun.
Article En | MEDLINE | ID: mdl-38721015

Background: Despite the increasing efficacy of chemotherapy (C), the 5-year survival rate for patients with unresectable colorectal liver metastases (CLM) remains around 10%. Liver transplantation (LT) might offer a curative approach for patients with liver-only disease, yet its superior efficacy compared to C alone remains to be demonstrated. Methods: The TransMet randomised multicentre clinical trial (NCT02597348) compares the curative potential of C followed by LT versus C alone in patients with unresectable CLM despite stable or responding disease on C. Patient eligibility criteria proposed by local tumour boards had to be validated by an independent committee via monthly videoconferences. Outcomes reported here are from a non-specified interim analysis. These include the eligibility of patients to be transplanted for non resectable colorectal liver metastases, as well as the feasibility and the safety of liver transplantation in this indication. Findings: From February 2016 to July 2021, 94 (60%) of 157 patients from 20 centres in 3 countries submitted to the validation committee, were randomised. Reasons for ineligibility were mainly tumour progression in 50 (32%) or potential resectability in 13 (8%). The median delay to LT after randomisation was 51 (IQR 30-65) days. Nine of 47 patients (19%, 95% CI: 9-33) allocated to the LT arm failed to undergo transplantation because of intercurrent disease progression. Three of the 38 transplanted patients (8%) were re-transplanted, one of whom (3%) died post-operatively from multi-organ failure. Interpretation: The selection process of potential candidates for curative intent LT for unresectable CLM in the TransMet trial highlighted the critical role of an independent multidisciplinary validation committee. After stringent selection, the feasibility of LT was 81%, as 19% had disease progression while on the waiting list. These patients should be given high priority for organ allocation to avoid dropout from the transplant strategy. Funding: No source of support or funding from any author to disclose for this work. The trial was supported by the Assistance Publique - Hôpitaux de Paris (AP-HP).

2.
Surg Endosc ; 2024 May 24.
Article En | MEDLINE | ID: mdl-38789622

BACKGROUND: It is assumed that robotic-assisted surgery (RAS) may facilitate complex pelvic dissection for rectal cancer compared to the laparoscopic-assisted resection (LAR). The aim of this study was to compare perioperative morbidity, short- and long-term oncologic, and functional outcomes between the RAS and LAR approaches. METHODS: Between 2015 and 2021, all rectal cancers operated on by (LAR) or (RAS) were retrospectively reviewed in two colorectal surgery centers. RESULTS: A total of 197 patients were included in the study, with 70% in the LAR group and 30% in the RAS group. The tumor location and stage were identical in both groups (not significant = NS). The overall postoperative mortality rate was not significantly different between the two groups. (0% LAR; 0.5% RAS; NS). The postoperative morbidity was similar between the two groups (60% LAR vs 57% RAS; NS). The number of early surgical re-interventions within the first 30 days was similar (10% for the LAR group and 3% for the RAS group; NS). The rate of complete TME was similar (88% for the LAR group and 94% for the RAS group; NS). However, the rate of circumferential R1 was significantly higher in the LAR group (13%) compared to the RAS group (2%) (p = 0.009). The 3-year recurrence rate did not differ between the two groups (77% for both groups; NS). After a mean follow-up of three years, the incidence of anterior resection syndrome was significantly lower in the LAR group compared to the RAS group (54 vs 76%; p = 0.030). CONCLUSIONS: The use of a RAS was found to be reliable for oncologic outcomes and morbidity. However, the expected benefits for functional outcomes were not observed. Therefore, the added value of RAS for rectal cancer needs to be reassessed in light of new laparoscopic technologies and patient management options.

3.
Hepatobiliary Pancreat Dis Int ; 22(6): 554-569, 2023 Dec.
Article En | MEDLINE | ID: mdl-36973111

BACKGROUND: Post-hepatectomy liver failure (PHLF) is a leading cause of postoperative mortality after liver surgery. Due to its significant impact, it is imperative to understand the risk stratification and preventative strategies for PHLF. The main objective of this review is to highlight the role of these strategies in a timeline centered way around curative resection. DATA SOURCES: This review includes studies on both humans and animals, where they addressed PHLF. A literature search was conducted across the Cochrane Library, Embase, MEDLINE/PubMed, and Web of Knowledge electronic databases for English language studies published between July 1997 and June 2020. Studies presented in other languages were equally considered. The quality of included publications was assessed using Downs and Black's checklist. The results were presented in qualitative summaries owing to the lack of studies qualifying for quantitative analysis. RESULTS: This systematic review with 245 studies, provides insight into the current prediction, prevention, diagnosis, and management options for PHLF. This review highlighted that liver volume manipulation is the most frequently studied preventive measure against PHLF in clinical practice, with modest improvement in the treatment strategies over the past decade. CONCLUSIONS: Remnant liver volume manipulation is the most consistent preventive measure against PHLF.


Liver Failure , Liver Neoplasms , Humans , Hepatectomy/adverse effects , Liver Neoplasms/surgery , Liver Failure/diagnosis , Liver Failure/etiology , Liver Failure/prevention & control , Liver Function Tests , Postoperative Complications/etiology , Postoperative Complications/surgery , Retrospective Studies
4.
iScience ; 26(1): 105714, 2023 Jan 20.
Article En | MEDLINE | ID: mdl-36691615

Partial liver removal is an important therapy option for liver cancer. In most patients within a few weeks, the liver is able to fully regenerate. In some patients, however, regeneration fails with often severe consequences. To better understand the control mechanisms of liver regeneration, experiments in mice were performed, guiding the creation of a spatiotemporal 3D model of the regenerating liver. The model represents cells and blood vessels within an entire liver lobe, a macroscopic liver subunit. The model could reproduce the experimental data only if a biomechanical growth control (BGC)-mechanism, inhibiting cell cycle entrance at high compression, was taken into account and predicted that BGC may act as a short-range growth inhibitor minimizing the number of proliferating neighbor cells of a proliferating cell, generating a checkerboard-like proliferation pattern. Model-predicted cell proliferation patterns in pigs and mice were found experimentally. The results underpin the importance of biomechanical aspects in liver growth control.

5.
Transplantation ; 107(3): 664-669, 2023 03 01.
Article En | MEDLINE | ID: mdl-36477606

BACKGROUND: In the current setting of organ shortage, brain-dead liver donors with recent liver trauma (RLT) represent a potential pool of donors. Yet, data on feasibility and safety of liver transplantation (LT) using grafts with RLT are lacking. METHODS: All liver grafts from brain-dead donors with RLT proposed for LT between 2010 and 2018 were identified from the nationwide CRISTAL registry of the Biomedicine Agency. The current study aimed at evaluating 1-y survival as the primary endpoint. RESULTS: Among 11 073 LTs, 142 LTs (1.3%) using grafts with RLT were performed. These 142 LTs, including 23 split LTs, were performed from 131 donors (46.1%) of 284 donors with RLT proposed for LT. Transplanted grafts were procured from donors with lower liver enzymes levels ( P < 0.001) and less advanced liver trauma according to the American Association for the Surgery of Trauma liver grading system ( P < 0.001) compared with not transplanted grafts. Before allocation procedures, 20 (7%) of 284 donors underwent damage control intervention. During transplantation, specific liver trauma management was needed in 19 patients (13%), consisting of local hemostatic control (n = 15), partial hepatic resection on back-table (n = 3), or perihepatic packing (n = 1). Ninety-day mortality and severe morbidity rates were 8.5% (n = 12) and 29.5% (n = 42), respectively. One-year overall and graft survival rates were 85% and 81%, and corresponding 5-y rates were 77% and 72%, respectively. CONCLUSIONS: Using liver grafts from donors with RLT seems safe with acceptable long-term outcomes. All brain-dead patients with multiorgan trauma, including liver injury, should be considered for organ allocation.


Liver Transplantation , Tissue and Organ Procurement , Wounds, Nonpenetrating , Humans , Liver Transplantation/adverse effects , Liver , Tissue Donors , Wounds, Nonpenetrating/etiology , Allografts , Graft Survival , Retrospective Studies
6.
Liver Transpl ; 28(11): 1716-1725, 2022 11.
Article En | MEDLINE | ID: mdl-35662403

In situ normothermic regional perfusion (NRP) and ex situ normothermic machine perfusion (NMP) aim to improve the outcomes of liver transplantation (LT) using controlled donation after circulatory death (cDCD). NRP and NMP have not yet been compared directly. In this international observational study, outcomes of LT performed between 2015 and 2019 for organs procured from cDCD donors subjected to NRP or NMP commenced at the donor center were compared using propensity score matching (PSM). Of the 224 cDCD donations in the NRP cohort that proceeded to asystole, 193 livers were procured, resulting in 157 transplants. In the NMP cohort, perfusion was commenced in all 40 cases and resulted in 34 transplants (use rates: 70% vs. 85% [p = 0.052], respectively). After PSM, 34 NMP liver recipients were matched with 68 NRP liver recipients. The two cohorts were similar for donor functional warm ischemia time (21 min after NRP vs. 20 min after NMP; p = 0.17), UK-Donation After Circulatory Death risk score (5 vs. 5 points; p = 0.38), and laboratory Model for End-Stage Liver Disease scores (12 vs. 12 points; p = 0.83). The incidence of nonanastomotic biliary strictures (1.5% vs. 2.9%; p > 0.99), early allograft dysfunction (20.6% vs. 8.8%; p = 0.13), and 30-day graft loss (4.4% vs. 8.8%; p = 0.40) were similar, although peak posttransplant aspartate aminotransferase levels were higher in the NRP cohort (872 vs. 344 IU/L; p < 0.001). NRP livers were more frequently allocated to recipients suffering from hepatocellular carcinoma (HCC; 60.3% vs. 20.6%; p < 0.001). HCC-censored 2-year graft and patient survival rates were 91.5% versus 88.2% (p = 0.52) and 97.9% versus 94.1% (p = 0.25) after NRP and NMP, respectively. Both perfusion techniques achieved similar outcomes and appeared to match benchmarks expected for donation after brain death livers. This study may inform the design of a definitive trial.


Carcinoma, Hepatocellular , End Stage Liver Disease , Liver Neoplasms , Liver Transplantation , Aspartate Aminotransferases , End Stage Liver Disease/surgery , Graft Survival , Humans , Liver Transplantation/methods , Organ Preservation/methods , Perfusion/methods , Severity of Illness Index
7.
Int J Mol Sci ; 23(9)2022 Apr 30.
Article En | MEDLINE | ID: mdl-35563381

Organ transplantation remains the treatment of last resort in case of failure of a vital organ (lung, liver, heart, intestine) or non-vital organ (essentially the kidney and pancreas) for which supplementary treatments exist. It remains the best alternative both in terms of quality-of-life and life expectancy for patients and of public health expenditure. Unfortunately, organ shortage remains a widespread issue, as on average only about 25% of patients waiting for an organ are transplanted each year. This situation has led to the consideration of recent donor populations (deceased by brain death with extended criteria or deceased after circulatory arrest). These organs are sensitive to the conditions of conservation during the ischemia phase, which have an impact on the graft's short- and long-term fate. This evolution necessitates a more adapted management of organ donation and the optimization of preservation conditions. In this general review, the different aspects of preservation will be considered. Initially done by hypothermia with the help of specific solutions, preservation is evolving with oxygenated perfusion, in hypothermia or normothermia, aiming at maintaining tissue metabolism. Preservation time is also becoming a unique evaluation window to predict organ quality, allowing repair and/or optimization of recipient choice.


Hypothermia , Tissue and Organ Procurement , Humans , Organ Preservation , Perfusion , Tissue Donors
8.
BMC Gastroenterol ; 22(1): 201, 2022 Apr 21.
Article En | MEDLINE | ID: mdl-35448953

BACKGROUND: Colorectal cancer is the third most common cancer in France and by the time of the diagnosis, 15-25% of patients will suffer from synchronous liver metastases. Surgery associated to neoadjuvant treatment can cure these patients, but few studies focus only on rectal cancer. This study was meant to compare the outcomes of patients who underwent a simultaneous resection to those who underwent a staged resection (rectum first or liver first) in the University Hospital of Tours, France. METHODS: We assessed retrospectively a prospective maintained data base about the clinical, pathological and survival outcomes of patients who underwent a simultaneous or a staged resection in our center between 2010 and 2018. A propensity score matching was used, considering the initial characteristics of our groups. RESULTS: There were 70 patients (55/15 males, female respectively) with median age 60 (54-68) years. After matching 48 (69%) of them underwent a staged approach and 22 (31%) a simultaneous approach were compared. After PSM, there were 22 patients in each group. No differences were found in terms of morbidity (p = 0.210), overall survival (p = 0.517) and disease-free survival (p = 0.691) at 3 years after matching. There were significantly less recurrences in the simultaneous group (50% vs 81.8%, p = 0.026). CONCLUSIONS: Simultaneous resection of the rectal primary cancer and synchronous liver metastases is safe and feasible with no difference in terms of survival.


Colorectal Neoplasms , Liver Neoplasms , Rectal Neoplasms , Colorectal Neoplasms/pathology , Female , Hepatectomy/adverse effects , Humans , Male , Middle Aged , Propensity Score , Prospective Studies , Rectal Neoplasms/surgery , Retrospective Studies , Treatment Outcome
9.
Clin Transplant ; 36(2): e14536, 2022 02.
Article En | MEDLINE | ID: mdl-34779019

In France, the program of controlled donation after circulatory death (cDCD) was established with routine use of in situ normothermic regional perfusion (NRP). There is currently no consensus on its optimal duration. The purpose was to assess the impact of NRP duration on liver graft function and biliary outcomes. One-hundred and fifty-six liver recipients from NRP-cDCD donors from six French centers between 2015 and 2019 were included. Primary endpoint was graft function assessed by early allograft dysfunction (EAD, according to Olthoff's criteria) and MEAF (model for early allograft function) score. Overall, three (1.9%) patients had primary non-function, 30 (19.2%) patients experienced EAD, and MEAF score was 7.3 (±1.7). Mean NRP duration was 179 (±43) min. There was no impact of NRP duration on EAD (170±44 min in patients with EAD vs. 181±42 min in patients without, P = .286). There was no significant association between NRP duration and MEAF score (P = .347). NRP duration did neither impact on overall biliary complications nor on non-anastomotic biliary strictures (overall rates of 16.7% and 3.9%, respectively). In conclusion, duration of NRP in cDCD donors does not seem to impact liver graft function and biliary outcomes after liver transplantation. A 1 to 4-h perfusion represents an optimal time window.


Liver Transplantation , Death , Graft Survival , Humans , Liver Transplantation/methods , Organ Preservation/methods , Perfusion/methods , Retrospective Studies , Tissue Donors
10.
Transplantation ; 106(7): 1411-1420, 2022 07 01.
Article En | MEDLINE | ID: mdl-34966104

BACKGROUND: The ABO blood group system may influence tumorigenesis, but its prognostic value in liver transplantation (LT) for hepatocellular carcinoma (HCC) has never been assessed. METHODS: All consecutive patients who underwent LT for HCC between 2013 and 2017 at 9 centers were analyzed. Predictors of tumor recurrence were identified using multivariable analysis, while comparison between group A and non-A recipients was performed after propensity score matching. RESULTS: Among 925 LT recipients, 406 were blood group A, 94 group B, 380 group O, and 45 group AB. On multivariable analysis, group A was associated with tumor recurrence (hazard ratio [HR] = 1.574 [95% confidence interval; 95% CI = 1.034-2.394] P = 0.034). After propensity score matching, 1- and 5-y recurrence rates were 7.4% and 20.1% in group A recipients versus 3.3% and 13.2% in non-A recipients (HR = 1.66 [95% CI = 1.12-2.45], P = 0.011). One and 5-y recurrence-free survivals were 85.2% and 66.8% in group A recipients versus 88.5% and 71.3% in non-A recipients (HR = 1.38 [95% CI = 1.01-1.90], P = 0.045). Among recipients within Milan criteria (n = 604), 1- and 5-y recurrence rates were 5.8% and 12.7% in group A recipients versus 3.1% and 12.2% in non-A recipients (HR = 1.197 [95% CI = 0.721-1.987], P = 0.485). Among recipients outside Milan criteria (n = 182), 1- and 5-y recurrence rates were 12.1% and 43.8% in group A recipients versus 3.9% and 15.6% in non-A recipients (HR = 3.175 [95% CI = 1.526-6.608], P = 0.002). CONCLUSIONS: ABO blood system influences the oncological outcome of recipients undergoing LT for HCC. Its incorporation in the prognostication model of LT for HCC may allow improving the management of LT candidates.


Carcinoma, Hepatocellular , Liver Neoplasms , Liver Transplantation , ABO Blood-Group System , Carcinoma, Hepatocellular/pathology , Humans , Liver Neoplasms/pathology , Liver Transplantation/adverse effects , Neoplasm Recurrence, Local/pathology , Retrospective Studies , Risk Factors
12.
Ann Surg ; 272(5): 751-758, 2020 11.
Article En | MEDLINE | ID: mdl-32833758

OBJECTIVE: To compare HOPE and NRP in liver transplantation from cDCD. SUMMARY OF BACKGROUND DATA: Liver transplantation after cDCD is associated with higher rates of graft loss. Dynamic preservation strategies such as NRP and HOPE may offer safer use of cDCD grafts. METHODS: Retrospective comparative cohort study assessing outcomes after cDCD liver transplantation in 1 Swiss (HOPE) and 6 French (NRP) centers. The primary endpoint was 1-year tumor-death censored graft and patient survival. RESULTS: A total of 132 and 93 liver grafts were transplanted after NRP and HOPE, respectively. NRP grafts were procured from younger donors (50 vs 61 years, P < 0.001), with shorter functional donor warm ischemia (22 vs 31 minutes, P < 0.001) and a lower overall predicted risk for graft loss (UK-DCD-risk score 6 vs 9 points, P < 0.001). One-year tumor-death censored graft and patient survival was 93% versus 86% (P = 0.125) and 95% versus 93% (P = 0.482) after NRP and HOPE, respectively. No differences in non-anastomotic biliary strictures, primary nonfunction and hepatic artery thrombosis were observed in the total cohort and in 32 vs. 32 propensity score-matched recipients CONCLUSION:: NRP and HOPE in cDCD achieved similar post-transplant recipient and graft survival rates exceeding 85% and comparable to the benchmark values observed in standard DBD liver transplantation. Grafts in the HOPE cohort were procured from older donors and had longer warm ischemia times, and consequently achieved higher utilization rates. Therefore, randomized controlled trials with intention-to-treat analysis are needed to further compare both preservation strategies, especially for high-risk donor-recipient combinations.


Cold Ischemia , Graft Rejection/prevention & control , Liver Transplantation , Organ Preservation/methods , Warm Ischemia , Cryopreservation , Delayed Graft Function , France , Graft Survival , Humans , Oxygen , Perfusion/methods , Retrospective Studies , Tissue Donors
13.
Transplantation ; 104(9): 1943-1951, 2020 09.
Article En | MEDLINE | ID: mdl-32639402

BACKGROUND: Liver transplantation (LT) from controlled donation after circulatory death (cDCD) was initiated in France in 2015 under a protocol based on the use of normothermic regional perfusion (NRP) before organ procurement. The aim was to compare outcomes following cDCD LT with NRP and donation after brain death (DBD) LT. METHODS: This is a multicenter retrospective study comparing cDCD LT with NRP and DBD LT. A case-matched study (1:2) was performed using the variables such as recipient and donor age, indication of LT. RESULTS: A total of 50 patients from the cDCD group were matched to 100 patients from the DBD group. From postoperative days 1-4, serum transaminase release was significantly lower in the cDCD group compared to the DBD group (P < 0.05). Early allograft dysfunction (cDCD: 18% versus DBD: 32%; P = 0.11), acute kidney injury (26% versus 33%; P = 0.49), 90-d graft loss (2% versus 5%; P = 0.66), and arterial (4% versus 12%; P = 0.19) and biliary (16% versus 17%; P = 0.94) complications were similar between the 2 groups. The 2-y graft survival was 88% for cDCD group and 85% for DBD group (P = 0.91). The 2-y patient survival was 90% for cDCD group and 88% for DBD group (P = 0.68). CONCLUSIONS: This study provides evidence that cDCD LT following postmortem NRP can be safely and effectively performed in selected recipients with similar graft and patient survival outcomes, without increased rates of biliary complications and early graft dysfunction compared to DBD LT.


Brain Death , Liver Transplantation/methods , Organ Preservation/methods , Perfusion/methods , Tissue Donors , Adult , Biliary Tract Diseases/epidemiology , Female , Graft Survival , Humans , Liver Transplantation/adverse effects , Liver Transplantation/mortality , Male , Middle Aged , Postoperative Complications/epidemiology , Retrospective Studies
14.
Chirurgia (Bucur) ; 115(2): 169-184, 2020.
Article En | MEDLINE | ID: mdl-32369721

The aim of this work was to review the entire literature on splenic surgery in cirrhotic patients in order to best define the surgical indications and their management specifics. A review of the international literature published between January 1995 and August 2015 was thus carried out.


Liver Cirrhosis/complications , Spleen/surgery , Splenectomy/methods , Splenic Diseases/surgery , Humans , Splenic Diseases/complications
15.
HPB (Oxford) ; 22(10): 1480-1489, 2020 10.
Article En | MEDLINE | ID: mdl-32156510

BACKGROUND/PURPOSE: Two-stage hepatectomy (TSH), is associated with a risk of drop-out due to tumoral progression following portal vein occlusion (PVO). We explored the impact of majorhepatectomy on tumor growth by objective radiological measures comparing to PVO and minor hepatectomy, using a model of bilobar colorectal liver metastasis (CLM). METHODS: CLM were induced in 48 BDIX rats by injection of DHDK12-cells. 7 days after cells injection, animals were distributed into 4 groups of equal number (n = 12): portal vein ligation (PVL), sham laparotomy (sham), minor (30%Phx) and major (70%Phx) hepatectomy. MR imaging was used for in vivo analysis of tumor implantation, growth and volumes. RESULTS: At POD10, tumour volumes were homogeneously distributed among the 4 groups. Lower TV were significantly observed after 70%Phx comparing to PVL at POD17 (0.63 ± 0.14cm3 vs 0.9 ± 0.16cm3, p = 0.008) and to the 3 others groups at POD24: 1.78 ± 0.38cm3 vs 3.2 ± 0.62cm3 (PVL, p = 0.019), 2.41 ± 0.74cm3 (Sham, p = 0.024) and 2.32 ± 0.59cm3 (30%PHx, p = 0.019). CONCLUSION: We confirmed in a reproducible model that contrary to PVO, a major hepatectomy decreases the growth of CLM in the remnant liver. This result leads to questioning the usual TSH and justifies exploring alternative strategies. The "major hepatectomy first-approach" should be an option to be evaluated.


Colorectal Neoplasms , Liver Neoplasms , Animals , Hepatectomy , Ligation , Liver/diagnostic imaging , Liver/surgery , Liver Neoplasms/diagnostic imaging , Liver Neoplasms/surgery , Liver Regeneration , Models, Theoretical , Portal Vein/diagnostic imaging , Portal Vein/surgery , Rats
16.
Am J Transplant ; 20(9): 2437-2448, 2020 09.
Article En | MEDLINE | ID: mdl-32185866

The aim of this study was to produce a prognostic model to help predict posttransplant survival in patients transplanted with grade-3 acute-on-chronic liver failure (ACLF-3). Patients with ACLF-3 who underwent liver transplantation (LT) between 2007 and 2017 in 5 transplant centers were included (n = 152). Predictors of 1-year mortality were retrospectively screened and tested on a single center training cohort and subsequently tested on an independent multicenter cohort composed of the 4 other centers. Four independent pretransplant risk factors were associated with 1-year mortality after transplantation in the training cohort: age ≥53 years (P = .044), pre-LT arterial lactate level ≥4 mml/L (P = .013), mechanical ventilation with PaO2 /FiO2  ≤ 200 mm Hg (P = .026), and pre-LT leukocyte count ≤10 G/L (P = .004). A simplified version of the model was derived by assigning 1 point to each risk factor: the transplantation for Aclf-3 model (TAM) score. A cut-off at 2 points distinguished a high-risk group (score >2) from a low-risk group (score ≤2) with 1-year survival of 8.3% vs 83.9% respectively (P < .001). This model was subsequently validated in the independent multicenter cohort. The TAM score can help stratify posttransplant survival and identify an optimal transplantation window for patients with ACLF-3.


Acute-On-Chronic Liver Failure , Liver Transplantation , Critical Illness , Humans , Liver Cirrhosis/surgery , Middle Aged , Prognosis , Retrospective Studies
17.
Ann Surg Oncol ; 26(13): 4445-4451, 2019 Dec.
Article En | MEDLINE | ID: mdl-31399820

BACKGROUND: Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a new technology for delivering intraperitoneal chemotherapy. It is generally assumed that with PIPAC, the ratio of peritoneal to systemic drug concentration is superior to liquid hyperthermic intraperitoneal chemotherapy (HIPEC). To date, no direct comparative data are available supporting such an assumption. MATERIALS AND METHODS: Twelve 65-day-old pigs were randomly separated into three groups of four pigs each, all of which received intraperitoneal chemotherapy using the following administration methods: PIPAC with oxaliplatin 92 mg in 150 ml dextrose 5% (Group 1); PIPAC with electrostatic aerosol precipitation (ePIPAC; Group 2); or laparoscopic HIPEC (L-HIPEC) with oxaliplatin 400 mg in 4 L dextrose 5% at 42 °C (Group 3). Serial blood and peritoneal tissue concentrations of oxaliplatin were determined by spectrometry. RESULTS: In all three groups, the maximum concentration of oxaliplatin in blood was detected 50-60 min after onset of the chemotherapy experiments, with no significant differences among the three groups (p = 0.7994). Blood oxaliplatin concentrations (0-30 min) were significantly higher in the L-HIPEC group compared with the ePIPAC group (p < 0.05). No difference was found for the overall systemic oxaliplatin absorption (area under the curve). Overall concentrations in the peritoneum were not different among the three groups (p = 0.4725), but were significantly higher in the visceral peritoneum in the PIPAC group (p = 0.0242). CONCLUSIONS: Blood and tissue concentrations were comparable between all groups; however, depending on the intraperitoneal area examined and the time points of drug delivery, the concentrations differed significantly between the three groups.


Hyperthermia, Induced , Oxaliplatin/administration & dosage , Oxaliplatin/pharmacokinetics , Aerosols/administration & dosage , Aerosols/pharmacokinetics , Animals , Laparoscopy , Peritoneum/metabolism , Swine , Tissue Distribution
18.
Eur Surg Res ; 60(1-2): 31-44, 2019.
Article En | MEDLINE | ID: mdl-30759434

BACKGROUND: The hepatic volume gain following resection is essential for clinical recovery. Previous studies have focused on cellular regeneration. This study aims to explore the rate of hepatic regeneration of the porcine liver following major resection, highlighting estimates of the early microarchitectural changes that occur during the cellular regeneration. METHODS: Nineteen large white pigs had 75% resection with serial measurements of the hepatic volume, density, blood flow, and architectural changes. RESULTS: The growth rate initially was 45% per day, then rapidly decreased and was accompanied by a similar pattern of hepatic fat deposition. The architectural changes showed a significant increase in the Ki67 expression (p < 0.0001) in the days following resection with a peak on the 2nd day and nearly normalized on day 7. The expression of CD31 increased significantly on the 2nd and 3rd days compared to the pre-resection samples (p = 0.03). Hepatic artery flow per liver volume remained at baseline ranges during regeneration. Portal flow per liver volume increased after liver resection (p < 0.001), was still elevated on the 1st postoperative day, then decreased. Correlations were significantly negative between the hepatic volume increase on day 3 and the hepatic oxygen consumption and the net lactate production at the end of the procedure (r = -0.82, p = 0.01, and r = -0.70, p = 0.03). CONCLUSION: The volume increase in the first days - a fast process - is not explained by cellular proliferation alone. The liver/body weight ratio is back to 50% of the preoperative value after 3 days to close to 100% volume regain on days 10-15.


Hepatectomy , Liver/pathology , Animals , Kinetics , Liver Regeneration , Swine
19.
Gastroenterol Res Pract ; 2018: 9628490, 2018.
Article En | MEDLINE | ID: mdl-30425737

BACKGROUND: Adhesive small bowel obstruction (SBO) represents a heavy burden in healthcare systems worldwide and is associated with significant morbidity and mortality. Although conservative treatment alone can lead to SBO resolution in most cases, its optimal duration is still a matter of debate. The aim of this study was to analyze different SBO evolution patterns in order to further determine when to switch to surgical treatment. STUDY DESIGN: All patients who were admitted for adhesive SBO between 2011 and 2016 were reviewed. Patients who had immediate surgery (IS), a successful medical treatment (SMT), and a failed medical treatment (FMT) were compared in terms of overall morbidity, mortality, and SBO recurrence. RESULTS: Overall 154 patients were identified, including 23 (14.9%) in IS, 27 (17.5%) in FMT, and 104 (67.6%) in SMT groups. In terms of comorbidities, patients were similar in all groups. Overall morbidity rates were highest in IS and FMT groups (30% and 33%, respectively, vs. 4% in the SMT group, p < 0.001) whereas mortality rate was highest in the FMT group (22% vs. 0% and 0% in IS and SMT groups, respectively, p < 0.001). SBO recurrence rate was highest in the SMT group (22% vs. 4% and 7% in IS and FMT groups, respectively, p = 0.042). CONCLUSION: FMT seems to be associated with similar overall morbidity compared with IS but with increased postoperative mortality. Patient frailty seems to be worsened by prolonged inefficient medical treatment.

20.
Hepatobiliary Pancreat Dis Int ; 17(6): 538-545, 2018 Dec.
Article En | MEDLINE | ID: mdl-30170983

BACKGROUND: The hepatic hemodynamics is an essential parameter in surgical planning as well as in various disease processes. The transit time ultrasound (TTUS) perivascular flow probe technology is widely used in clinical practice to evaluate the hepatic inflow, yet invasive. The phase-contrast-MRI (PC-MRI) is not invasive and potentially applicable in assessing the hepatic blood flow. In the present study, we compared the hepatic inflow rates using the PC-MRI and the TTUS probe, and evaluated their predictive value of post-hepatectomy adverse events. METHODS: Eighteen large white pigs were anaesthetized for PC-MRI and approximately 75% hepatic resection was performed under a unified protocol. The blood flow was measured in the hepatic artery (Qha), the portal vein (Qpv), and the aorta above the celiac trunk (Qca) using PC-MRI, and was compared to the TTUS probe. The Bland-Altman method was conducted and a partial least squares regression (PLS) model was implemented. RESULTS: The mean Qpv measured in PC-MRI was 0.55 ±â€¯0.12 L/min, and in the TTUS probe was 0.74 ±â€¯0.17 L/min. Qca was 1.40 ±â€¯0.47 L/min in the PC-MRI and 2.00 ±â€¯0.60 L/min in the TTUS probe. Qha was 0.17 ±â€¯0.10 L/min in the PC-MRI, and 0.13 ±â€¯0.06 L/min in the TTUS probe. The Bland-Altman method revealed that the estimated bias of Qca in the PC-MRI was 32% (95% CI: -49% to 15%); Qha 17% (95% CI: -15% to 51%); and Qpv 40% (95% CI: -62% to 18%). The TTUS probe had a higher weight in predicting adverse outcomes after 75% resection compared to the PC-MRI (ß= 0.35 and 0.43 vs ß = 0.22 and 0.07, for tissue changes and premature death, respectively). CONCLUSIONS: There is a tendency of the PC-MRI to underestimate the flow measured by the TTUS probes. The TTUS probe measures are more predictive of relevant post-hepatectomy outcomes.


Hepatectomy/adverse effects , Liver Circulation , Magnetic Resonance Imaging/methods , Ultrasonography/methods , Animals , Female , Hepatic Artery/diagnostic imaging , Models, Animal , Portal Vein/diagnostic imaging , Swine
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