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1.
Langenbecks Arch Surg ; 408(1): 105, 2023 Feb 25.
Article in English | MEDLINE | ID: mdl-36840760

ABSTRACT

BACKGROUND: Kidney transplantation (KT) has become the standard of care for patients with end-stage renal disease. However, as atherosclerosis progresses with time on dialysis, it causes increasing difficulties in implanting the graft. This is a comparative study analyzing complications and graft survival of recipients with iliac revascularization before transplantation. METHODS: Between January 2006 and December 2015, 1691 kidney transplants were performed at our institution. We retrospectively analyzed eighteen patients with peripheral arterial disease (PAD) with the necessity of vascular revascularization before kidney transplantation to protect the inflow to the renal graft and to optimizing blood supply to the extremities. The primary endpoint included patient survival and graft survival. The secondary endpoints evaluate perioperative and early postoperative complication rates after kidney transplantation. RESULTS: All patients enrolled in this study underwent two consecutive surgical procedures. No patient reported limb loss, and there was no additional perioperative morbidity or mortality related to the vascular procedure. Primary endpoints such as graft survival without dialysis and overall patient survival show 1-month survival of 100%, 1-year survival of 94.1%, and 5-year survival of 84.70%, respectively. One graft failure occurred 8 months after transplantation due to acute rejection, and there were two deaths over follow-up period due to myocardial infarction. CONCLUSIONS: Vascular repair before kidney transplantation is safe, and results are suggestive that it prolongs graft survival. These promising results should encourage other centers to address vascular repair before the transplantation to optimize blood supply to the extremity and the future graft. Although, the interpretation of our results must be cautiously because of the small and heterogeneous sample size, and the limitations of retrospective study design. Prospective trials with larger study populations are needed to confirm the results of this study and to identify significant differences.


Subject(s)
Atherosclerosis , Kidney Failure, Chronic , Kidney Transplantation , Humans , Kidney Transplantation/methods , Retrospective Studies , Prospective Studies , Kidney Failure, Chronic/surgery , Graft Survival , Treatment Outcome
2.
Ann Surg Oncol ; 2022 May 12.
Article in English | MEDLINE | ID: mdl-35552929

ABSTRACT

BACKGROUND: Leiomyosarcoma (LMS) most frequently metastasizes to the lung. Metastatic LMS is considered incurable. Selected patients may benefit from pulmonary metastasectomy (PM) within multimodal therapy. This study analyzed the prognostic relevance of clinicopathologic factors in these patients. METHODS: Patients with metastatic LMS to the lung treated in our center from 2004 to 2020 were included in this single-center retrospective study. Overall survival (OS), progression-free survival (PFS), and prognostic factors were analyzed. RESULTS: The study had 64 patients (33 males, 52%) with metastatic LMS to the lung. The 5-year OS was 55% after the diagnosis of pulmonary metastases. Age older than 60 years at the primary tumor diagnosis, primary tumor larger than 70 mm, and five or more lung metastases were associated with poorer OS. Of the 64 patients, 44 underwent PM. The postoperative mortality rate was 0%. The patients selected for PM were younger and had smaller primary tumors, fewer metastases, and metastases that more often were metachronous. Metastasis grade (G1 vs. G2/3) and size (20-mm cutoff) were significant prognostic factors for OS (p = 0.05) and PFS (p = 0.028) after PM, respectively. The 44 patients who underwent PM had a survival benefit compared with the patients who were selected but did not undergo PM (n = 6) and the patients who were not selected for PM (n = 14). Three patients (7%) were alive and free of disease at the last follow-up visit respectively 5.5, 9, and 12 years after PM. CONCLUSIONS: For patients with leiomyosarcoma, PM is safe. Despite aggressive multimodal treatment, most patients will experience recurrence and eventually die of their disease. However, a small subgroup of patients could potentially be cured after PM.

3.
Eur J Clin Invest ; 52(2): e13691, 2022 Feb.
Article in English | MEDLINE | ID: mdl-34747502

ABSTRACT

BACKGROUND: Sudden restoration of normothermic conditions upon reperfusion of cold-stored grafts has been suggested to entail a massive energy demand not yet met by the cells that still suffer from hypothermic torpor. An adapted and gentle rise of graft temperature by ex-vivo machine perfusion has, therefore, been proposed. This should now be tested in the clinical setting. METHODS: In a first clinical series, six ECD-kidneys were subjected to controlled oxygenated rewarming (COR) during short term pre-implantation machine perfusion. Matched kidneys that were conventionally kept on ice served as controls. RESULTS: Early allograft function after transplantation was significantly improved by COR. On post-operative day 7, clearance of creatinine was more than twofold higher after COR and fractional excretion of sodium in the normal range, while significantly elevated in control kidneys. Good correlations were seen between ulterior graft function and real-time parameters obtained during pre-transplant machine perfusion (Lactate: r2  = .9; TIMP2: r2  = .74). Conventional denominators of graft viability like kidney donor risk index KDRI were far less predictive (r2  = .26). CONCLUSION: It is concluded that COR can be safely applied to renal grafts and appears to be a valuable tool to predict and improve early renal function after transplantation.


Subject(s)
Kidney Transplantation , Oxygen , Reperfusion , Rewarming/methods , Adult , Aged , Female , Humans , Kidney Transplantation/methods , Male , Middle Aged , Pilot Projects , Preoperative Period , Prospective Studies
4.
Clin Transplant ; 36(3): e14543, 2022 03.
Article in English | MEDLINE | ID: mdl-34813125

ABSTRACT

BACKGROUND: HTK-N was developed based on the traditional HTK preservation solution, resulting in stronger protection against reactive oxygen species as well as better tolerance to hypothermia and ischemia. Aim of the present study was to compare HTK-N to HTK in clinical kidney transplantation demonstrating safety and non-inferiority. METHODS: We performed a randomized controlled single blinded clinical phase II trial in patients undergoing living donor kidney transplantation. After retroperitoneoscopic nephrectomy kidneys were either perfused and stored with classical HTK solution or the new HTK-N solution. Primary endpoint was the glomerular filtration rate (eGFR according to CKD EPI) 3 months after transplantation. Secondary endpoints included graft and patient survival beside others. RESULTS: The study included 42 patients, of which 22 were randomized in the HTK-N group and 20 in the HTK group. The primary end point showed a mean eGFR of 55.4 ± 14.0 ml/min/1.73 m2 in the HTK group compared to a GFR of 57.2 ± 16.7 ml/min/m2 in the HTK-N group (P = .72). Regarding secondary endpoints, there were no apparent differences. Posttransplant graft and patient survival was 100%. CONCLUSION: This study is the first clinical application of HTK-N for kidney preservation and demonstrates non-inferiority compared to HTK in the setting of living donor kidney transplantation.


Subject(s)
Living Donors , Organ Preservation , Humans , Insulin , Kidney , Organ Preservation/methods , Pilot Projects
5.
Curr Opin Organ Transplant ; 27(5): 446-453, 2022 10 01.
Article in English | MEDLINE | ID: mdl-35857331

ABSTRACT

PURPOSE OF REVIEW: This review aims to summarize the latest original preclinical and clinical articles in the setting of normothermic machine perfusion (NMP) of kidney grafts. RECENT FINDINGS: Kidney NMP can be safely translated into the clinical routine and there is increasing evidence that NMP may be beneficial in graft preservation especially in marginal kidney grafts. Due to the near-physiological state during NMP, this technology may be used as an ex-vivo organ assessment and treatment platform. There are reports on the application of mesenchymal stromal/stem cells, multipotent adult progenitor cells and microRNA during kidney NMP, with first data indicating that these therapies indeed lead to a decrease in inflammatory response and kidney injury. Together with the demonstrated possibility of prolonged ex-vivo perfusion without significant graft damage, NMP could not only be used as a tool to perform preimplant graft assessment. Some evidence exists that it truly has the potential to be a platform to treat and repair injured kidney grafts, thereby significantly reducing the number of declined organs. SUMMARY: Kidney NMP is feasible and can potentially increase the donor pool not only by preimplant graft assessment, but also by ex-vivo graft treatment.


Subject(s)
Kidney Transplantation , Organ Preservation , Adult , Humans , Kidney , Kidney Transplantation/adverse effects , Organ Preservation/adverse effects , Perfusion , Tissue Donors
6.
Am J Transplant ; 20(4): 1192-1195, 2020 04.
Article in English | MEDLINE | ID: mdl-31599063

ABSTRACT

Cold preservation sensitizes organ grafts to exacerbation of tissue injury upon reperfusion. This reperfusion injury is not fully explained by the mere re-introduction of oxygen but rather is pertinent to the immediate rise in metabolic turnover associated with the abrupt restoration of normothermia. Here we report the first clinical case of gradual resumption of graft temperature upon ex vivo machine perfusion from hypothermia up to normothermic conditions using cell-free buffer as a perfusate. A kidney graft from an extended criteria donor was put on the machine after 12.5 hours of cold storage. During ex vivo perfusion, perfusion pressure and temperature were gradually elevated from 30 mm Hg and 8°C to 75 mm Hg and 35°C, respectively. Perfusate consisted of diluted Steen solution, oxygenated with 100% oxygen. Final flow rates at 35°C were 850 mL/min. The kidney was transplanted without complications and showed good immediate function. Serum creatinine fell from preoperative 720 µmol/L to 506 µmol/L during the first 24 hours after transplantation. Clearance after 1 week was 43.1 mL/min. Controlled oxygenated rewarming prior to transplantation can be performed up to normothermia without blood components or artificial oxygen carriers and may represent a promising tool to mitigate cold-induced reperfusion injury or to evaluate graft performance.


Subject(s)
Kidney Transplantation , Rewarming , Humans , Kidney/surgery , Organ Preservation , Perfusion
7.
Liver Transpl ; 24(9): 1209-1220, 2018 09.
Article in English | MEDLINE | ID: mdl-30146768

ABSTRACT

Portal vein thrombosis (PVT) is a severe complication after liver transplantation that can result in increased morbidity and mortality. Few data are available regarding risk factors, classification, and treatment of PVT after living donor liver transplantation (LDLT). Between January 2004 and November 2014, 421 adult-to-adult LDLTs were performed at our institution, and they were included in the analysis. Perioperative characteristics and outcomes from patients with no-PVT (n = 393) were compared with those with de novo PVT (total portal vein thrombosis [t-PVT]; n = 28). Ten patients had early portal vein thrombosis (e-PVT) occurring within 1 month, and 18 patients had late portal vein thrombosis (l-PVT) appearing later than 1 month after LDLT. Analysis of perioperative variables determined that splenectomy was associated with t-PVT (hazard ratio [HR], 3.55; P = 0.01), e-PVT (HR, 4.96; P = 0.04), and l-PVT (HR, 3.84; P = 0.03). In contrast, donor age was only found as a risk factor for l-PVT (HR, 1.05; P = 0.01). Salvage rate for treatment in e-PVT and l-PVT was 100% and 50%, respectively, without having an early event of rethrombosis. Mortality within 30 days did not show a significant difference between groups (no-PVT, 2% versus e-PVT, 10%; P = 0.15). No significant differences were found regarding 1-year (89% versus 92%), 5-year (79% versus 82%), and 10-year (69% versus 79%) graft survival between the t-PVT and no-PVT groups, respectively (P = 0.24). The 1-year (89% versus 96%), 5-year (82% versus 86%), and 10-year (79% versus 83%) patient survival was similar for the patients in the no-PVT and t-PVT groups, respectively (P = 0.70). No cases of graft loss occurred as a direct consequence of PVT. In conclusion, the early diagnosis and management of PVT after LDLT can lead to acceptable early and longterm results without affecting patient and graft survival.


Subject(s)
Liver Transplantation/adverse effects , Living Donors , Portal Vein , Splenectomy/adverse effects , Venous Thrombosis/etiology , Adult , Female , Graft Survival , Humans , Liver Circulation , Liver Transplantation/methods , Liver Transplantation/mortality , Male , Middle Aged , Ontario , Portal Vein/diagnostic imaging , Portal Vein/physiopathology , Retrospective Studies , Risk Assessment , Risk Factors , Splenectomy/mortality , Time Factors , Treatment Outcome , Vascular Patency , Venous Thrombosis/diagnostic imaging , Venous Thrombosis/mortality , Venous Thrombosis/physiopathology
8.
Artif Organs ; 42(6): 647-654, 2018 Jun.
Article in English | MEDLINE | ID: mdl-29607529

ABSTRACT

The concept of "controlled oxygenated rewarming" (COR) using ex vivo machine perfusion after cold storage was evaluated as tool to improve renal graft function after transplantation. Renal function after 20 min warm ischemia and 21 h cold storage was studied in an auto-transplant model in pigs (25-30 kg, n = 6 per group). In the study group, preimplant ex vivo machine perfusion for 90 min was added after cold storage, including gentle warming up of the graft to 20°C (COR). Kidneys that were only cold stored for 21 h served as controls. In vivo follow up was one week; the remaining native kidney was removed during transplantation. COR significantly improved cortical microcirculation upon early reperfusion and reduced free radical mediated injury and cellular apoptosis. Post-transplant kidney function (peak levels in serum) was also largely and significantly improved in comparison to the control group. A weak inverse correlation was found between renal flow during COR and later peak creatinine after transplantation (r2 = 0.5), better values were seen for oxygen consumption, measured during machine perfusion at 20°C (r2 = 0.81). Gentle graft rewarming prior to transplantation by COR improves post-transplant graft outcome and may also be a valuable adjunct in pretransplant graft assessment.


Subject(s)
Kidney Transplantation/methods , Kidney/physiology , Organ Preservation/methods , Oxygen/metabolism , Warm Ischemia/methods , Animals , Female , Graft Survival , Kidney/blood supply , Kidney/pathology , Kidney/ultrastructure , Oxygen Consumption , Perfusion/methods , Swine
9.
Ann Surg ; 263(5): 979-85, 2016 May.
Article in English | MEDLINE | ID: mdl-26106842

ABSTRACT

OBJECTIVE: To compare the outcome of adult live donor liver transplantation (LDLT) with grafts from older versus younger donors. INTRODUCTION: Using older donor grafts for adult LDLT may help expand the donor pool. However, the risks of LDLT with older donors remain controversial, and many centers are reluctant to use live donors aged 45 years or older for adult LDLT. METHODS: Outcomes of patients receiving a LDLT graft from donors aged 50 years or older (n = 91) were compared with those receiving a live donor graft from donors younger than 50 years (n = 378). RESULTS: Incidences of biliary (LDLT <50: 24% vs LDLT ≥50: 23%; P = 0.89) and major complications (LDLT <50: 24% vs LDLT ≥50: 24%; P = 1) were similar between both groups of recipients. No difference was observed in 30-day recipient mortality (LDLT <50: 3% vs LDLT ≥50: 0%; P = 0.13). The 1- (90% vs 90%), 5- (82% vs 73%), and 10- (71% vs 58%) year graft survival was statistically similar between both groups (P = 0.075). Likewise, patient survival after 1- (92% vs 96%), 5- (83% vs 79%), and 10- (76% vs 69%) years was also similar (P = 0.686). Overall, donors rate of major complications (Dindo-Clavien ≥3b) within 30 days was low (n = 2.3%) and not different in older versus younger donors (P = 1). Donor median hospital stay in both groups was identical [LDLT <50: 6 (4-17) vs LDLT ≥50: 6 (4-14) days; P = 0.65]. No donor death occurred and all donors had full recovery and returned to baseline activity. CONCLUSIONS: Right lobe LDLT with donors aged 50 years or older results in acceptable recipient outcome without increased donor morbidity or mortality. Potential live donors should not be declined on the basis of age alone.


Subject(s)
Liver Transplantation , Living Donors , Adolescent , Adult , Age Factors , Biomarkers/analysis , Female , Graft Survival , Humans , Length of Stay/statistics & numerical data , Liver Transplantation/mortality , Male , Middle Aged , Postoperative Complications/mortality , Prospective Studies , Treatment Outcome
10.
Clin Transplant ; 28(1): 37-46, 2014 Jan.
Article in English | MEDLINE | ID: mdl-24171713

ABSTRACT

This is the first matched pair analysis on the puzzling clinical problem of whether to perform liver transplantation (LT) or liver resection (LR) for Child's A hepatocellular carcinoma (HCC) patients. A total of 201 patients diagnosed with HCC and Child's A liver cirrhosis were treated with LT transarterial chemoembolization (TACE) or LR between 1998 and 2012. To achieve the most accurate study design, two groups of 57 patients were matched retrospectively according to their tumor characteristics detected by the initial computerized tomography (CT) scan. Sixteen of 57 LT candidates were not transplanted due to tumor progress during pre-treatment (TACE). Nevertheless, the retrospective analysis of the matched pairs according to the intention-to-treat principle resulted in a better five-yr overall survival (OS) rate of 54.3% for the group of LT candidates compared with 35.7% for those receiving LR (p = 0.19). In patients meeting the University of California, San Francisco (UCSF) criteria, five-yr OS reached 58.4% after LT and 45.1% after LR (p = 0.56). For Milan criteria (MC) patients, LT resulted in 57.9% and LR in 42% five-yr OS rate (p = 0.29). In conclusion, the finding of a better OS rate in LT was not statistically significant. There was also a selection bias in favor of LT, which may have influenced the OS. Therefore, particularly in regard to organ scarcity, LR remains a viable treatment option for respectable HCC in Child's A cirrhosis.


Subject(s)
Carcinoma, Hepatocellular/surgery , Hepatectomy , Intention to Treat Analysis , Liver Cirrhosis/surgery , Liver Neoplasms/surgery , Liver Transplantation , Adult , Aged , Aged, 80 and over , Carcinoma, Hepatocellular/mortality , Female , Follow-Up Studies , Humans , Liver Cirrhosis/mortality , Liver Neoplasms/mortality , Male , Matched-Pair Analysis , Middle Aged , Prognosis , Recurrence , Retrospective Studies , Survival Rate
11.
Thorac Cardiovasc Surg ; 61(3): 267-9, 2013 Apr.
Article in English | MEDLINE | ID: mdl-23344754

ABSTRACT

A 54-year-old man was admitted to our clinic due to elevated γ-glutamyltransferase, without any clinical symptoms. About 25 years ago, he had undergone blunt abdominal and thoracic trauma during an accident. No diagnostic measures or therapy had been performed at that time. Serum bilirubin was normal, but the values for alanine transaminase, aspartate transaminase, and alkaline phosphatase were slightly above the reference range. Sonography of the abdomen revealed dilated intrahepatic bile ducts up to 3 mm in diameter and steatosis of the liver grade I. CT scan and MRI of the thorax and abdomen showed a giant hiatal hernia with transposition of upper abdominal organs into the chest. As the patient presented clinically completely asymptomatic, without dyspnea, dysfunction of phonation or ingestion, we decided a conservative treatment with Ursodesoxycholic acid. The liver values resolved with this regimen gradually. At follow-up examination 1 year later, they had normalized. Spirometry showed a reduced lung capacity (3.44 L; 64.4% of the desired value) and a reduced FEV1 (forced expiratory volume in one second) of 2.84 L (70.2% of the desired value). Further diagnostics revealed normal otorhinolaryngological and phoniatric findings including stroboscopy of the vocal folds and voice range profile.


Subject(s)
Abdominal Injuries/diagnosis , Diaphragm/injuries , Wounds, Nonpenetrating/diagnosis , Diagnosis, Differential , Follow-Up Studies , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Rupture/diagnosis , Tomography, X-Ray Computed
12.
Curr Oncol ; 30(6): 5849-5862, 2023 06 17.
Article in English | MEDLINE | ID: mdl-37366921

ABSTRACT

Klatskin tumors have a bad prognosis despite aggressive therapy. The role and extent of lymph node dissection during surgery is a matter of discussion. This retrospective study analyzes our current experience of surgical treatments in the last decade. Patients and Methods: A retrospective single-center analysis of patients (n = 317) who underwent surgical treatment for Klatskin tumors. Univariable and multivariable logistic regression and Cox proportional analysis were performed. The primary endpoint was to investigate the role of lymph node metastasis for patient survival after complete tumor resection. The secondary endpoint was the prediction of lymph node status and long-term survival from preoperatively available parameters. Results: In patients with negative resection margins, a negative lymph node status was the prognosis-determining factor with a 1-, 3-, and 5-year survival rate of 87.7%, 37%, and 26.4% compared with 69.5%, 13.9%, and 9.3% for lymph-node-positive patients, respectively. Multivariable logistic regression for complete resection and negative lymph node status demonstrated only Bismuth type 4 (p = 0.01) and tumor grading (p = 0.002) as independent predictors. In multivariate Cox regression analysis, independent predictors of survival after surgery were the preoperative bilirubin level (p = 0.03), intraoperative transfusion (p = 0.002), and tumor grading (G) (p = 0.001). Conclusion: Lymph node dissection is of utmost importance for adequate staging in patients undergoing surgery for perihilar cholangiocarcinoma. In spite of extensive surgery, long-term survival is clearly associated with the aggressiveness of the disease.


Subject(s)
Bile Duct Neoplasms , Klatskin Tumor , Humans , Klatskin Tumor/surgery , Klatskin Tumor/pathology , Retrospective Studies , Neoplasm Staging , Bile Duct Neoplasms/surgery , Lymph Nodes/pathology
13.
Transplantation ; 106(5): 973-978, 2022 05 01.
Article in English | MEDLINE | ID: mdl-34172643

ABSTRACT

BACKGROUND: Normothermic machine perfusion (NMP) provides a promising strategy for preservation and conditioning of marginal organ grafts. However, at present, high logistic effort limits normothermic renal perfusion to a short, postponed machine perfusion at site of the recipient transplant center. Thus, organ preservation during transportation still takes place under hypothermic conditions, leading to significantly reduced efficacy of NMP. Recently, it was shown that gentle and controlled warming up of cold stored kidneys compensates for hypothermic induced damage in comparison to end ischemic NMP. This study aims to compare controlled oxygenated rewarming (COR) with continuous upfront normothermic perfusion in a porcine model of transplantation. METHODS: Following exposure to 30 min of warm ischemia, kidneys (n = 6/group) were removed and either cold stored for 8 h (cold storage [CS]), cold stored for 6 h with subsequent controlled rewarming up to 35 °C for 2 h (COR), or directly subjected to 8 h of continuous NMP. Kidney function was evaluated using a preclinical autotransplant model with follow-up for 7 d. RESULTS: NMP and COR both improved renal function in comparison to CS and displayed similar serum creatinine and urea levels during follow-up. COR resulted in less tenascin C expression in the tissue compared with CS, indicating reduced proinflammatory upregulation in the graft by gentle rewarming. CONCLUSIONS: COR seems to be a potential alternative in clinical application of NMP, thereby providing logistic ease and usability.


Subject(s)
Rewarming , Transplants , Animals , Cold Ischemia/adverse effects , Kidney/physiology , Organ Preservation/methods , Perfusion/adverse effects , Perfusion/methods , Rewarming/methods , Swine
14.
Eur J Radiol ; 155: 110470, 2022 Oct.
Article in English | MEDLINE | ID: mdl-35985092

ABSTRACT

PURPOSE: We aimed to analyze the diagnostic accuracy of preoperative CT-guided biopsy to identify patients that might profit from neoadjuvant chemotherapy in a specialized high-volume sarcoma center. MATERIAL AND METHODS: We retrospectively reviewed all patients with suspected soft tissue tumors of the abdomen cavity including the retroperitoneum, who received CT-guided biopsy followed by surgical tumor resection. Sensitivity, specificity, PPV and NPV were calculated in all patients with abdominal sarcomas at our hospital. A subgroup analysis was performed for patients with liposarcoma. RESULTS: A total of 82 patients (35 female, 47 male, age: 62.0 ± 14.7) received preoperative CT-guided biopsy followed by surgical resection. Overall accordance of CT-guided biopsy to identify final histology was 77 %. CT-guided biopsy revealed the diagnosis of liposarcoma in 23 patients whereas final analysis of the surgical specimen identified liposarcoma in 29 patients. Here, sensitivity, specificity, PPV and NPV was 79.3 %, 100.0 %, 100.0 % and 89.8 % respectively. Subgroup analysis revealed a better accuracy for correctly identifying patients with well-differentiated liposarcoma than patients with dedifferentiated liposarcoma (75.0 % vs 62.5 %). In patients with other sarcoma, sensitivity, specificity, PPV, NPV and diagnostic accuracy was 87.5 %, 95.5 %, 82.4 % and 96.9 %, respectively. CONCLUSION: CT-guided biopsy in a specialized high-volume sarcoma center is an accurate and effective method to assess patients with abdominal sarcoma and especially abdominal liposarcoma. Therefore, it is an indispensable tool in the pretherapeutic workup process. Nevertheless, our study underlines the previously reported difficulties in dedifferentiated liposarcoma diagnostics, whereby these patient cohort would profit the most from a neoadjuvant therapy regime.


Subject(s)
Liposarcoma , Retroperitoneal Neoplasms , Sarcoma , Soft Tissue Neoplasms , Aged , Female , Humans , Image-Guided Biopsy , Liposarcoma/diagnostic imaging , Liposarcoma/surgery , Male , Middle Aged , Retroperitoneal Neoplasms/diagnostic imaging , Retroperitoneal Neoplasms/surgery , Retrospective Studies , Sarcoma/diagnostic imaging , Sarcoma/pathology , Sarcoma/surgery , Tomography, X-Ray Computed
15.
Cancers (Basel) ; 14(22)2022 Nov 09.
Article in English | MEDLINE | ID: mdl-36428589

ABSTRACT

Circulating tumor DNA (ctDNA) from circulating free DNA (cfDNA) in GIST is of interest for the detection of heterogeneous resistance mutations and treatment monitoring. However, methodologies for use in a local setting are not standardized and are error-prone and difficult to interpret. We established a workflow to evaluate routine tumor tissue NGS (Illumina-based next generation sequencing) panels and pipelines for ctDNA sequencing in an academic setting. Regular blood collection (Sarstedt) EDTA tubes were sufficient for direct processing whereas specialized tubes (STRECK) were better for transportation. Mutation detection rate was higher in automatically extracted (AE) than manually extracted (ME) samples. Sensitivity and specificity for specific mutation detection was higher using digital droplet (dd)PCR compared to NGS. In a retrospective analysis of NGS and clinical data (133 samples from 38 patients), cfDNA concentration correlated with tumor load and mutation detection. A clinical routine pipeline and a novel research pipeline yielded different results, but known and resistance-mediating mutations were detected by both and correlated with the resistance spectrum of TKIs used. In conclusion, NGS routine panel analysis was not sensitive and specific enough to replace solid biopsies in GIST. However, more precise methods (hybridization capture NGS, ddPCR) may comprise important research tools to investigate resistance. Future clinical trials need to compare methodology and protocols.

16.
Transplant Direct ; 7(10): e751, 2021 Oct.
Article in English | MEDLINE | ID: mdl-34514106

ABSTRACT

The increased usage of marginal grafts has triggered interest in perfused kidney preservation to minimize graft injury. We used a donation after circulatory death (DCD) porcine kidney autotransplantation model to compare 3 of the most frequently used ex vivo kidney perfusion techniques: nonoxygenated hypothermic machine perfusion (non-oxHMP), oxygenated hypothermic machine perfusion (oxHMP), and normothermic ex vivo kidney perfusion (NEVKP). METHODS: Following 30 min of warm ischemia, grafts were retrieved and preserved with either 16 h of non-oxHMP, oxHMP, or NEVKP (n = 5 per group). After contralateral nephrectomy, grafts were autotransplanted and animals were followed for 8 d. Kidney function and injury markers were compared between groups. RESULTS: NEVKP demonstrated a significant reduction in preservation injury compared with either cold preservation method. Grafts preserved by NEVKP showed superior function with lower peak serum creatinine (NEVKP versus non-oxHMP versus oxHMP: 3.66 ± 1.33 mg/dL, 8.82 ± 3.17 mg/dL, and 9.02 ± 5.5 mg/dL) and more rapid recovery. The NEVKP group demonstrated significantly increased creatinine clearance on postoperative day 3 compared with the cold perfused groups. Tubular injury scores on postoperative day 8 were similar in all groups. CONCLUSIONS: Addition of oxygen during HMP did not reduce preservation injury of DCD kidney grafts. Grafts preserved with prolonged NEVKP demonstrated superior initial graft function compared with grafts preserved with non-oxHMP or oxHMP in a model of pig DCD kidney transplantation.

17.
Transplantation ; 102(8): 1262-1270, 2018 08.
Article in English | MEDLINE | ID: mdl-29683999

ABSTRACT

BACKGROUND: Cold storage is poorly tolerated by kidney grafts retrieved after donation after circulatory death. It has been determined that normothermic ex vivo kidney perfusion (NEVKP) preservation decreases injury by minimizing cold ischemic storage. The impact of NEVKP on warm ischemic injury is unknown. METHODS: We compared pig kidneys retrieved after 30 minutes warm ischemia and immediate transplantation (no-preservation) with grafts that were exposed to 30 minutes of warm ischemia plus 8-hour NEVKP or plus 8-hour static cold storage (SCS). RESULTS: After transplantation, the NEVKP group demonstrated lower daily serum creatinine levels indicating better early graft function compared with no-preservation (P = 0.02) or SCS group (P < 0.001). In addition, NEVKP preserved grafts had a significantly lower grade of tubular injury and interstitial inflammation 30 minutes after reperfusion compared to grafts without any storage (injury score, NEVKP 1-2 vs no-preservation, 2-2, P = 0.029; inflammation score, NEVKP, 0-0.5 vs no-preservation, 1-2; P = 0.002), although it did not reach significance level when compared to the SCS group (injury score, 1-2, P = 0.071; inflammation score, 1-1; P = 0.071). Regeneration was assessed 30 minutes after reperfusion by Ki-67 staining. The NEVKP group demonstrated significantly higher number of Ki-67-positive cells: 9.2 ± 3.7 when compared with SCS group (3.9 ± 1.0, P = 0.015) and no-preservation group (4.2 ± 0.7, P = 0.04). CONCLUSIONS: In this porcine model of donation after circulatory death kidney transplantation NEVKP reduced kidney injury and improved graft function when compared with no-preservation. The results suggest that NEVKP does not cause additional damage to grafts during the preservation period, but may reverse the negative effects of warm ischemic insult itself and promotes regeneration.


Subject(s)
Death , Kidney Transplantation/methods , Organ Preservation , Perfusion , Warm Ischemia/adverse effects , Animals , Aorta/pathology , Cold Ischemia , Disease Models, Animal , Kidney , Organ Preservation Solutions/pharmacology , Regeneration , Reperfusion Injury/physiopathology , Swine , Time Factors
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