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1.
Transpl Int ; 37: 12263, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38550626

RESUMEN

ABO-incompatible (ABOi) living kidney transplantation (KTx) is an established procedure to address the demand for kidney transplants with outcomes comparable to ABO-compatible KTx. Desensitization involves the use of immunoadsorption (IA) to eliminate preformed antibodies against the allograft. This monocentric retrospective study compares single-use antigen-selective Glycosorb® ABO columns to reusable non-antigen-specific Immunosorba® immunoglobulin adsorption columns regarding postoperative infectious complications and outcome. It includes all 138 ABOi KTx performed at Freiburg Transplant Center from 2004-2020. We compare 81 patients desensitized using antigen-specific columns (sIA) to 57 patients who received IA using non-antigen-specific columns (nsIA). We describe distribution of infections, mortality and allograft survival in both groups and use Cox proportional hazards regression to test for the association of IA type with severe infections. Desensitization with nsIA tripled the risk of severe postoperative infections (adjusted HR 3.08, 95% CI: 1.3-8.1) compared to sIA. nsIA was associated with significantly more recurring (21.4% vs. 6.2%) and severe infections (28.6% vs. 8.6%), mostly in the form of urosepsis. A significantly higher proportion of patients with sIA suffered from allograft rejection (29.6% vs. 14.0%). However, allograft survival was comparable. nsIA is associated with a two-fold risk of developing a severe postoperative infection after ABOi KTx.


Asunto(s)
Trasplante de Riñón , Humanos , Trasplante de Riñón/efectos adversos , Trasplante de Riñón/métodos , Estudios Retrospectivos , Sistema del Grupo Sanguíneo ABO , Incompatibilidad de Grupos Sanguíneos , Factores de Riesgo , Rechazo de Injerto , Supervivencia de Injerto , Donadores Vivos
2.
Langenbecks Arch Surg ; 409(1): 129, 2024 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-38632147

RESUMEN

BACKGROUND: Pancreatoduodenectomies are complex surgical procedures with a considerable morbidity and mortality even in high-volume centers. However, postoperative morbidity and long-term oncological outcome are not only affected by the surgical procedure itself, but also by the underlying disease. The aim of our study is an analysis of pancreatoduodenectomies for patients with pancreatic ductal adenocarcinoma (PDAC) and ampullary carcinoma (CAMP) concerning postoperative complications and long-term outcome in a tertiary hospital in Germany. METHODS: The perioperative and oncological outcome of 109 pancreatic head resections performed for carcinoma of the ampulla vateri was compared to the outcome of 518 pancreatic head resections for pancreatic ductal adenocarcinoma over a 20 year-period from January 2002 until December 2021. All operative procedures were performed at the University Hospital Freiburg, Germany. Patient data was analyzed retrospectively, using a prospectively maintained SPSS database. Propensity score matching was performed to adjust for differences in surgical and reconstruction technique. Primary outcome of our study was long-term overall survival, secondary outcomes were postoperative complications and 30-day postoperative mortality. Postoperative complications like pancreatic fistula (POPF), postpancreatectomy hemorrhage (PPH) and delayed gastric emptying (DGE) were graded following current international definitions. Survival was estimated using Kaplan Meier curves and log-rank tests. A p-value < 0.05 was considered statistically significant. RESULTS: Operation time was significantly longer in PDAC patients (432 vs. 391 min, p < 0.001). The rate of portal vein resections was significantly higher in PDAC patients (p < 0.001). In CAMP patients, a pancreatogastrostomy as reconstruction technique was performed more frequently compared to PDAC patients (48.6% vs. 29.9%, p < 0.001) and there was a trend towards more laparoscopic surgeries in CAMP patients (p = 0.051). After propensity score matching, we found no difference in DGE B/C and PPH B/C (p = 0.389; p = 0.517), but a significantly higher rate of clinically relevant pancreatic fistula (CR-POPF) in patients with pancreatoduodenectomies due to ampullary carcinoma (30.7% vs. 16.8%, p < 0.001). Long-term survival was significantly better in CAMP patients (42 vs. 24 months, p = 0.003). CONCLUSION: Patients with pancreatoduodenectomies due to ampullary carcinomas showed a better long-term oncological survival, by reason of the better prognosis of this tumor entity. However, these patients often needed a more elaborated postoperative treatment due to the higher rate of clinically relevant pancreatic fistula in this group.


Asunto(s)
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Fístula Pancreática/etiología , Estudios Retrospectivos , Pronóstico , Neoplasias Pancreáticas/cirugía , Pancreaticoduodenectomía/métodos , Carcinoma Ductal Pancreático/patología , Complicaciones Posoperatorias/etiología
3.
Clin Transplant ; 37(3): e14880, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36522802

RESUMEN

BACKGROUND: Early patient and allograft survival after liver transplantation (LT) depend primarily on parenchymal function, but long-term allograft success relies often on biliary-tree function. We examined parameters related to cholangiocyte damage that predict poor long-term LT outcomes after donation after brain death (DBD). METHODS: Sixty bile ducts (BD) were assessed by a BD damage-score and divided into groups with "major" BD-damage (n = 33) and "no relevant" damage (n = 27) during static cold storage. Patients with "major" BD damage were further investigated by measuring biliary excretion parameters in the first 14 days post-LT (followed-up for 60-months). RESULTS: Patients who received LT showing "major" BD damage had significantly worse long-term patient survival, versus grafts with "no relevant" damage (p = .03). When "major" BD damage developed, low bilirubin levels (p = .012) and high gamma-glutamyl transferase (GGT)/bilirubin ratio (p = .0003) were evident in the early post-LT phase (7-14 days) in patients who survived (> 60 months), compared to those who did not. "High risk" patients with bile duct damage and low GGT/bilirubin ratio had significantly shorter overall survival (p < .0001). CONCLUSIONS: Once "major" BD damage occurs, a high GGT/bilirubin ratio in the early post-operative phase is likely indicator of liver and cholangiocyte regeneration, and thus a harbinger of good overall outcomes. "Major" BD damage without markers of regeneration identifies LT patients that could benefit from future repair therapies.


Asunto(s)
Trasplante de Hígado , Humanos , Conductos Biliares , Bilirrubina , Biomarcadores , Hígado , Trasplante de Hígado/efectos adversos
4.
Langenbecks Arch Surg ; 408(1): 363, 2023 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-37721586

RESUMEN

BACKGROUND: To evaluate recurrence in patients with post-neoadjuvant pathological complete response (pCR) and in patients with complete response of primary tumor but persisting lymphatic spread of disease (non-pCR, ypT0ypN +) of esophageal cancer. METHODS: Seventy-five patients (63 pCR, 12 non-pCR) were analyzed retrospectively. Pattern and incidence of local and distant recurrence as well as the impact on overall (OS) and disease-free survival (DFS) were evaluated. The efficacy of neoadjuvant chemotherapy according to FLOT protocol was compared to neoadjuvant chemoradiation according to CROSS protocol. RESULTS: In the pCR group, isolated local recurrence was diagnosed in 3%, while no isolated local recurrence was observed in the non-pCR group due to the high incidence of distant recurrence. Distant recurrence was most common in both cohorts (isolated distant recurrence: pCR group 10% to non-pCR group 55%; simultaneous distant and local recurrence: pCR group 3% to non-pCR group 18%). Median time to distant recurrence was 5.5 months, and median time to local recurrence was 8.0 months. Cumulative incidence of distant recurrence (with and without simultaneous local recurrence) was 16% (± 6%) in pCR patients and 79% (± 13%) in non-pCR patients (hazard ratio (HR) 0.123) estimated by Kaplan-Meier method. OS (HR 0.231) and DFS (HR 0.226) were significantly improved in patients with pCR compared to patients with non-pCR. Advantages for FLOT protocol compared to CROSS protocol, especially with regard to distant control of disease (HR 0.278), were observed (OS (HR 0.361), DFS (HR 0.226)). CONCLUSION: Distant recurrence is the predominant site of treatment failure in patients with pCR and non-pCR grade 1a regression, whereby recurrence rates are much higher in patients with non-pCR.


Asunto(s)
Neoplasias Esofágicas , Terapia Neoadyuvante , Humanos , Estudios Retrospectivos , Neoplasias Esofágicas/terapia , Supervivencia sin Enfermedad , Insuficiencia del Tratamiento
5.
Dis Esophagus ; 36(7)2023 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-36572398

RESUMEN

To evaluate pathological complete response (pCR, ypT0ypN0) after neoadjuvant treatment compared with non-complete response (non-CR) in patients with esophageal cancer (EC), and 393 patients were retrospectively analyzed. Survival probability was analyzed in patients with: (i) pCR vs non-CR; (ii) complete response of the primary tumor but persisting lymphatic metastases (non-CR-T0N+) and (iii) pCR and tumor-free lymphnodes exhibiting signs of postneoadjuvant regression vs. no signs of regression. (i) Median overall survival (mOS) was favorable in patients with pCR (pCR: mOS not reached vs. non-CR: 41 months, P < 0.001). Multivariate analysis revealed that grade of regression was not an independent predictor for prolonged survival. Instead, the achieved postneoadjuvant TNM-stage (T-stage: Hazard ratio [HR] ypT3-T4 vs. ypT0-T2: 1.837; N-stage: HR ypN1-N3 vs. ypN0: 2.046; Postneoadjuvant M-stage: HR ypM1 vs. ycM0: 2.709), the residual tumor (R)-classification (HR R1 vs. R0: 4.195) and the histologic subtype of EC (HR ESCC vs. EAC: 1.688) were prognostic factors. Patients with non-CR-T0N+ have a devastating prognosis, similar to those with local non-CR and lymphatic metastases (non-CR-T + N+) (non-CR-T0N+: 22.0 months, non-CR-T + N-: mOS not reached, non-CR-T + N+: 23.0 months; P-values: non-CR-T0N+ vs. non-CR-T + N-: 0.016; non-CR-T0N+ vs. non-CR-T + N+: 0.956; non-CR-T + N- vs. non-CR-T + N+: <0.001). Regressive changes in lymphnodes after neoadjuvant treatment did not influence survival-probability in patients with pCR (mOS not reached in each group; EAC-patients: P = 0.0919; ESCC-patients: P = 0.828). Particularly, the achieved postneoadjuvant ypTNM-stage influences the survival probability of patients with EC. Patients with non-CR-T0N+ have a dismal prognosis, and only true pathological complete response with ypT0ypN0 offers superior survival probabilities.


Asunto(s)
Neoplasias Esofágicas , Terapia Neoadyuvante , Humanos , Estudios Retrospectivos , Estadificación de Neoplasias , Metástasis Linfática , Terapia Combinada , Pronóstico , Neoplasias Esofágicas/patología
6.
Pediatr Radiol ; 53(11): 2305-2308, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37612542

RESUMEN

Portal vein arterialization is a rarely used, temporary surgical salvage solution to prevent biliary and hepatic ischemia and necrosis in acute liver de-arterialization. However, it can induce portal hypertension, causing increased morbidity and mortality. We report the case of a 5-year-old girl with portal hypertension and right ventricle volume overload following the creation of an iliacoportal shunt graft for portal vein arterialization due to vessel-adhering neuroblastoma. Partial shunt graft closure was accomplished by placing a stent graft in an hourglass configuration via the right femoral artery using two slender-sheaths in a line with the second more distal than the first. Subsequently, the patient's symptoms of right ventricle volume overload and portal hypertension decreased. In conclusion, endovascular reduction of elevated portal blood flow after portal vein arterialization is feasible, even in pediatric patients.


Asunto(s)
Hipertensión Portal , Trasplante de Hígado , Femenino , Humanos , Niño , Preescolar , Vena Porta/diagnóstico por imagen , Vena Porta/cirugía , Hipertensión Portal/diagnóstico por imagen , Hipertensión Portal/cirugía , Prótesis e Implantes
7.
J Hepatol ; 77(2): 397-409, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35367533

RESUMEN

BACKGROUND & AIMS: Despite recent translation of immunotherapies into clinical practice, the immunobiology of hepatocellular carcinoma (HCC), in particular the role and clinical relevance of exhausted and liver-resident T cells remain unclear. We therefore dissected the landscape of exhausted and resident T cell responses in the peripheral blood and tumor microenvironment of patients with HCC. METHODS: Lymphocytes were isolated from the blood, tumor and tumor-surrounding liver tissue of patients with HCC (n = 40, n = 10 treated with anti-PD-1 therapy). Phenotype, function and response to anti-PD-1 were analyzed by mass and flow cytometry ex vivo and in vitro, tissue residence was further assessed by immunohistochemistry and imaging mass cytometry. Gene signatures were analyzed in silico. RESULTS: We identified significant enrichment of heterogeneous populations of exhausted CD8+ T cells (TEX) in the tumor microenvironment. Strong enrichment of severely exhausted CD8 T cells expressing multiple immune checkpoints in addition to PD-1 was linked to poor progression-free and overall survival. In contrast, PD-1 was also expressed on a subset of more functional and metabolically active CD103+ tissue-resident memory T cells (TRM) that expressed few additional immune checkpoints and were associated with better survival. TEX enrichment was independent of BCLC stage, alpha-fetoprotein levels or age as a variable for progression-free survival in our cohort. These findings were in line with in silico gene signature analysis of HCC tumor transcriptomes from The Cancer Genome Atlas. A higher baseline TRM/TEX ratio was associated with disease control in anti-PD-1-treated patients. CONCLUSION: Our data provide information on the role of peripheral and intratumoral TEX-TRM dynamics in determining outcomes in patients with HCC. The dynamics between exhausted and liver-resident T cells have implications for immune-based diagnostics, rational patient selection and monitoring during HCC immunotherapies. LAY SUMMARY: The role of the immune response in hepatocellular carcinoma (HCC) remains unclear. T cells can mediate protection against tumor cells but are frequently dysfunctional and exhausted in cancer. We found that patients with a predominance of exhausted CD8+ T cells (TEX) had poor survival compared to patients with a predominance of tissue-resident memory T cells (TRM). This correlated with the molecular profile, metabolic and functional status of these cell populations. The enrichment of TEX was independently associated with prognosis in addition to disease stage, age and tumor markers. A high TRM proportion was also associated with better outcomes following checkpoint therapy. Thus, these T-cell populations are novel biomarkers with relevance in HCC.


Asunto(s)
Carcinoma Hepatocelular , Internado y Residencia , Neoplasias Hepáticas , Linfocitos T CD8-positivos , Humanos , Microambiente Tumoral
8.
Langenbecks Arch Surg ; 407(3): 1173-1182, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-35020083

RESUMEN

PURPOSE: Although Ogilvie's syndrome was first described about 70 years ago, its etiology and pathogenesis are still not fully understood. But more importantly, it is also not clear when to approach which therapeutic strategy. METHODS: Patients who were diagnosed with Ogilvie's syndrome at our institution in a 17-year time period (2002-2019) were included and retrospectively evaluated regarding different therapeutical strategies: conservative, endoscopic, or surgical. RESULTS: The study included 71 patients with 21 patients undergoing conservative therapy, 25 patients undergoing endoscopic therapy, and 25 patients undergoing surgery. However, 38% of patients (n = 8) who were primarily addressed for conservative management failed and had to undergo endoscopy or even surgery. Similarly, 8 patients (32%) with primarily endoscopic treatment had to proceed for surgery. In logistic regression analysis, only a colon diameter ≥ 11 cm (p = 0.01) could predict a lack of therapeutic success by endoscopic treatment. Ninety-day mortality and overall survival were comparable between the groups. CONCLUSION: As conservative and endoscopic management fail in about one-third of patients, a cutoff diameter ≥ 11 cm may be an adequate parameter to evaluate surgical therapy.


Asunto(s)
Seudoobstrucción Colónica , Seudoobstrucción Colónica/diagnóstico , Seudoobstrucción Colónica/cirugía , Tratamiento Conservador/efectos adversos , Endoscopía , Humanos , Estudios Retrospectivos
9.
Langenbecks Arch Surg ; 407(3): 1225-1232, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-35043258

RESUMEN

BACKGROUND: Acute mesenteric ischemia (AMI) is an uncommon, but life-threatening clinical entity due to late diagnosis resulting in irreversible ischemic bowel necrosis. The most common causes of AMI are the embolic occlusion and the acute thrombosis of the mesenteric circulation. Typical treatment is composed of an early revascularization of the mesenteric circulation followed by abdominal surgery for resection of nonviable intestine and restoration of the intestinal continuity, but the mortality rates remain high. METHODS: A retrospective cohort analysis was conducted, aiming to evaluate clinical characteristics, performed surgical procedures and outcomes of patients with acute mesenteric ischemia who underwent emergency abdominal surgery at a high volume surgical center in Germany. RESULTS: Overall, 53 patients were identified with the intraoperatively proven diagnosis of AMI. Overall hospital mortality was with 62% comparable to the literature. Nineteen patients presented with an intraoperatively verified complete and non-reversible intestinal infarction without any angiographic or surgical option for a revascularization of the mesenteric circulation or an option for intestinal resection. From the rest of the patients, 14 underwent intestinal resection of the ischemic area without restoration of intestinal continuity; the other 20 underwent resection with a primary anastomosis to restore intestinal continuity. The mortality rate of these patients with curative-intended surgery remained high (41% of patients died). Pre- and postoperative hyperlactatemia were associated with lower survival of these patients. CONCLUSION: AMI remains a life-threatening abdominal emergency. Therapeutic approaches are highly depended on acting surgeon's decision, being affected by subjectively rated bowel viability and physical condition of the affected patient. Only selected patients with good bowel viability appear to be suitable for receiving primary anastomosis. The results clearly indicate the need for further research to develop therapeutic approaches for a better management of AMI and to improve outcome of affected patients.


Asunto(s)
Isquemia Mesentérica , Enfermedad Aguda , Angiografía/efectos adversos , Humanos , Isquemia/etiología , Isquemia Mesentérica/complicaciones , Isquemia Mesentérica/cirugía , Estudios Retrospectivos , Resultado del Tratamiento , Procedimientos Quirúrgicos Vasculares/efectos adversos
10.
BMC Surg ; 22(1): 312, 2022 Aug 11.
Artículo en Inglés | MEDLINE | ID: mdl-35953811

RESUMEN

BACKGROUND: Etiology of hyperlactatemia in ICU patients is heterogeneous-septic, cardiogenic or hemorrhagic shock seem to be predominant reasons. Multiple studies show hyperlactatemia as an independent predictor for ICU mortality. Only limited data exists about the etiology of hyperlactatemia and lactate clearance and their influence on mortality. The goal of this single-center retrospective study, was to evaluate the effect of severe hyperlactatemia and reduced lactate clearance rate on the outcome of unselected ICU surgical patients. METHODS: Overall, 239 surgical patients with severe hyperlactatemia (> 10 mmol/L) who were treated in the surgical ICU at the University Medical Center Freiburg between June 2011 and August 2017, were included in this study. The cause of the hyperlactatemia as well as the postoperative course and the patient morbidity and mortality were retrospectively analyzed. Lactate clearance was calculated by comparing lactate level 12 h after first measurement of > 10 mmol/L. RESULTS: The overall mortality rate in our cohort was 82.4%. Severe hyperlactatemia was associated with death in the ICU (p < 0.001). The main etiologic factor was sepsis (51.9%), followed by mesenteric ischemia (15.1%), hemorrhagic shock (13.8%) and liver failure (9.6%). Higher lactate levels at ICU admission were associated with increased mortality (p < 0.001). Lactate clearance after 12 h was found to predict ICU mortality (ANOVA p < 0.001) with an overall clearance of under 50% within 12 h. The median percentage of clearance was 60.3% within 12 h for the survivor and 29.1% for the non-survivor group (p < 0.001). CONCLUSION: Lactate levels appropriately reflect disease severity and are associated with short-term mortality in critically ill patients. The main etiologic factor for surgical patients is sepsis. When elevated lactate levels persist more than 12 h, survival chances are low and the benefit of continued maximum therapy should be evaluated.


Asunto(s)
Hiperlactatemia , Sepsis , Choque Hemorrágico , Humanos , Hiperlactatemia/etiología , Ácido Láctico , Pronóstico , Estudios Retrospectivos
11.
Int J Mol Sci ; 23(5)2022 Mar 03.
Artículo en Inglés | MEDLINE | ID: mdl-35269922

RESUMEN

Colorectal cancer remains one of the most important health challenges in our society. The development of cancer immunotherapies has fostered the need to better understand the anti-tumor immune mechanisms at play in the tumor microenvironment and the strategies by which the tumor escapes them. In this review, we provide an overview of the molecular interactions that regulate tumor inflammation. We particularly discuss immunomodulatory cell-cell interactions, cell-soluble factor interactions, cell-extracellular matrix interactions and cell-microbiome interactions. While doing so, we highlight relevant examples of tumor immunomodulation in colorectal cancer.


Asunto(s)
Neoplasias Colorrectales , Inmunomodulación , Neoplasias Colorrectales/terapia , Humanos , Inmunidad , Inmunoterapia , Microambiente Tumoral
12.
Zentralbl Chir ; 147(2): 196-208, 2022 Apr.
Artículo en Alemán | MEDLINE | ID: mdl-35378559

RESUMEN

This review provides a summary of important, completed and published clinical trials, together with interesting and important running RCTs in pancreatic surgery.Randomised controlled studies (RCT) are one of the most important sources of new evidence for the treatment of cancer patients. This is particularly the case for pancreas surgery, where complications are comparatively common and serious and innovative surgical techniques and peri-interventional innovations are needed that could reduce morbidity and mortality. Although there are many very different methodological challenges in performing surgical RCTs, large surgical RCTs of high scientific quality have been completed during the last 10 years.


Asunto(s)
Procedimientos Quirúrgicos del Sistema Digestivo , Humanos , Páncreas/cirugía , Ensayos Clínicos Controlados Aleatorios como Asunto , Proyectos de Investigación
13.
HPB (Oxford) ; 24(2): 267-276, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-34294522

RESUMEN

BACKGROUND: Caroli Disease (CD) and Caroli Syndrome (CS) are rare disorders presenting with dilation of the intrahepatic bile ducts. CD/CS are associated with cholangiocarcinoma (CCA). However, the true incidence of CCA is still unclear, although it may serve as an indication for surgery. In this paper, we analyzed (I) the incidence of CCA in German centers, (II) reviewed our single center population together with its clinical presentation and (III) performed a thorough literature review. METHODS: 17 large HPB-centers across Germany were contacted and their patients after surgical treatment due to CD/CS with histopathology were included. Medline search for all studies published in English or German literature was performed. Patients who underwent surgery at our department between 2012 and 2020 due to CD or CS were analyzed. RESULTS: In the multicenter study, 79 patients suffered from CD and 119 patients from CS, with a total number of 198 patients. In 14 patients, CCA was found (Overall: 7,1%; CD: 6,3%, CS 7,6%). Between 2012 and 2020, 1661 liver resections were performed at our department. 14 patients underwent surgery due to CD or CS. Histological examination showed synchronous cholangiocarcinoma in one patient. The literature review revealed a CCA-rate of 7,3% in large series, whereas in case reports a rate of 6,8% was found. CONCLUSION: There is risk of malignant transformation and patients with CD might also benefit from resection due to improvement of symptoms. Therefore, resection is strongly advised. As certain patients with CS require transplantation, treatment should not be guided by the relatively low rate of CCA but by the concomitant diseases that come along with hepatic failure.


Asunto(s)
Neoplasias de los Conductos Biliares , Enfermedad de Caroli , Colangiocarcinoma , Neoplasias de los Conductos Biliares/diagnóstico , Neoplasias de los Conductos Biliares/epidemiología , Neoplasias de los Conductos Biliares/cirugía , Conductos Biliares Intrahepáticos/patología , Enfermedad de Caroli/complicaciones , Enfermedad de Caroli/epidemiología , Enfermedad de Caroli/cirugía , Colangiocarcinoma/diagnóstico , Colangiocarcinoma/epidemiología , Colangiocarcinoma/cirugía , Hepatectomía/efectos adversos , Humanos
14.
Eur J Immunol ; 50(12): 2041-2054, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-32640051

RESUMEN

The purpose of this study was to elucidate whether DC NK lectin group receptor-1 (DNGR-1)-dependent cross-presentation of dead-cell-associated antigens occurs after transplantation and contributes to CD8+ T cell responses, chronic allograft rejection (CAR), and fibrosis. BALB/c or C57BL/6 hearts were heterotopically transplanted into WT, Clec9a-/- , or Batf3-/- recipient C57BL/6 mice. Allografts were analyzed for cell infiltration, CD8+ T cell activation, fibrogenesis, and CAR using immunohistochemistry, Western blot, qRT2 -PCR, and flow cytometry. Allografts displayed infiltration by recipient DNGR-1+ DCs, signs of CAR, and fibrosis. Allografts in Clec9a-/- recipients showed reduced CAR (p < 0.0001), fibrosis (P = 0.0137), CD8+ cell infiltration (P < 0.0001), and effector cytokine levels compared to WT recipients. Batf3-deficiency greatly reduced DNGR-1+ DC-infiltration, CAR (P < 0.0001), and fibrosis (P = 0.0382). CD8 cells infiltrating allografts of cytochrome C treated recipients, showed reduced production of CD8 effector cytokines (P < 0.05). Further, alloreactive CD8+ T cell response in indirect pathway IFN-γ ELISPOT was reduced in Clec9a-/- recipient mice (P = 0.0283). Blockade of DNGR-1 by antibody, similar to genetic elimination of the receptor, reduced CAR (P = 0.0003), fibrosis (P = 0.0273), infiltration of CD8+ cells (p = 0.0006), and effector cytokine levels. DNGR-1-dependent alloantigen cross-presentation by DNGR-1+ DCs induces alloreactive CD8+ cells that induce CAR and fibrosis. Antibody against DNGR-1 can block this process and prevent CAR and fibrosis.


Asunto(s)
Aloinjertos/inmunología , Presentación de Antígeno/inmunología , Antígenos de Superficie/inmunología , Reactividad Cruzada/inmunología , Células Dendríticas/inmunología , Rechazo de Injerto/inmunología , Lectinas Tipo C/inmunología , Receptores Inmunológicos/inmunología , Animales , Linfocitos T CD8-positivos/inmunología , Femenino , Interferón gamma/inmunología , Activación de Linfocitos/inmunología , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL
15.
Pancreatology ; 21(5): 965-974, 2021 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-33832820

RESUMEN

BACKGROUND: Minimally invasive surgery is a field of rapid development. Evidence from randomized controlled trials in visceral surgery however still falls short of attesting unequivocal superiority to laparoscopic procedures over conventional open approaches with regard to postoperative outcome. The aim of this study was to explore the perioperative immune status of patients undergoing hybrid minimally invasive or conventional open pancreatoduodenectomy in a prospective cohort study. MATERIAL AND METHODS: Subtyping, quantification and functional analysis of circulating immune cells and determination of cytokine-levels in blood samples from patients receiving either hybrid minimally invasive (laPD) or conventional open pancreatoduodenectomy (oPD) was performed. Samples were taken from 29 patients (laPD: n = 14, oPD: n = 15) prior, during and up to six weeks after surgery. Cells were analyzed by flow cytometry, cytokines/chemokines were measured by proximity extension and enzyme-linked immunoassays. RESULTS: Open surgery induced higher levels of circulating inflammatory CD14++CD16+ intermediate monocytes. In contrast, hybrid minimally invasive resection was accompanied by increased numbers of circulating regulatory CD4+CD25+CD127low T-cells and by a reduced response of peripheral blood CD3+CD4+ T-cell populations to superantigen stimulation. Yet, rates of postoperative morbidity and infectious complications were similar. CONCLUSIONS: In summary, the results of this exploratory study may suggest a more balanced postoperative inflammatory response and a better-preserved immune regulation after hybrid minimally invasive pancreatoduodenectomy when compared to open surgery. Whether these results may translate to or be harnessed for improved patient outcome needs to be determined by future studies including larger cohorts and fully laparoscopic or robotic procedures.


Asunto(s)
Laparoscopía , Pancreaticoduodenectomía , Estudios de Cohortes , Humanos , Procedimientos Quirúrgicos Mínimamente Invasivos , Complicaciones Posoperatorias/epidemiología , Estudios Prospectivos
16.
Liver Int ; 41(1): 180-191, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-32997886

RESUMEN

BACKGROUND: Tumour recurrence is common after resection of intrahepatic cholangiocarcinoma (ICC). Repeated resection is a potential curative treatment, but outcomes are not well-defined thus far. The aim of this retrospective multicentre cohort study was to show the feasibility and survival of repeated resection of ICC recurrence. METHODS: Data were collected from 18 German hepato-pancreatico-biliary centres for patients who underwent repeated exploration of recurrent ICC between January 2008 and December 2017. Primary end points were overall (OS) and recurrence-free survival from the day of primary and repeated resection. RESULTS: Of 156 patients who underwent repeated exploration for recurrent ICC, 113 underwent re-resection. CA19-9 prior to primary resection, R status of first liver resection and median time to recurrence were significant determinants of repeated resectability. Median OS in the repeated resection group was 65.2 months, with consecutive 1-, 3- and 5-year OS of 98%, 78% and 57% respectively. After re-exploration, median OS from primary resection was 46.7 months, with a consecutive 1-, 3- and 5-year OS of 95%, 55% and 22% respectively. From the day of repeated resection, the median OS was 36.8 months, with a consecutive 1-, 3- and 5-year OS of 86%, 51% and 34% respectively. Minor morbidity (grade I+II) was present in 27%, grade IIIa-IVb morbidity in 20% and mortality in 3.5% of patients. CONCLUSION: Repeated resection of ICC has acceptable morbidity and mortality and seems to be associated with improved long-term survival. Structured follow-up after resection of ICC is necessary for early identification of these patients.


Asunto(s)
Neoplasias de los Conductos Biliares , Colangiocarcinoma , Neoplasias de los Conductos Biliares/cirugía , Colangiocarcinoma/cirugía , Estudios de Cohortes , Hepatectomía , Humanos , Recurrencia Local de Neoplasia/cirugía , Estudios Retrospectivos , Resultado del Tratamiento
17.
Langenbecks Arch Surg ; 406(7): 2521-2525, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34611750

RESUMEN

PURPOSE: Hiatal hernias with intrathoracic migration of the intestines are serious complications after minimally invasive esophageal resection with gastric sleeve conduit. High recurrence rates have been reported for standard suture hiatoplasties. Additional mesh reinforcement is not generally recommended due to the serious risk of endangering the gastric sleeve. We propose a safe, simple, and effective method to close the hiatal defect with the ligamentum teres. METHODS: After laparoscopic repositioning the migrated intestines, the ligamentum teres is dissected from the ligamentum falciforme and the anterior abdominal wall. It is then positioned behind the left lobe of the liver and swung toward the hiatal orifice. Across the anterior aspect of the hiatal defect it is semi-circularly fixated with non-absorbable sutures. Care should be taken not to endanger the blood supply of the gastric sleeve. RESULTS: We have used this technique for a total of 6 patients with hiatal hernias after hybrid minimally invasive esophageal resection in the elective (n = 4) and emergency setting (n = 2). No intraoperative or postoperative complications have been observed. No recurrence has been reported for 3 patients after 3 months. CONCLUSION: Primary suture hiatoplasties for hiatal hernias after minimally invasive esophageal resection can be technically challenging, and high postoperative recurrence rates are reported. An alternative, safe method is needed to close the hiatal defect. Our promising preliminary experience should stimulate further studies regarding the durability and efficacy of using the ligamentum teres hepatis to cover the hiatal defect.


Asunto(s)
Hernia Hiatal , Laparoscopía , Ligamentos Redondos , Gastrectomía , Hernia Hiatal/diagnóstico por imagen , Hernia Hiatal/cirugía , Herniorrafia/efectos adversos , Humanos , Recurrencia , Ligamentos Redondos/cirugía , Mallas Quirúrgicas
18.
BMC Surg ; 21(1): 35, 2021 Jan 13.
Artículo en Inglés | MEDLINE | ID: mdl-33435947

RESUMEN

BACKGROUND: Guidelines do not recommend surgery for patients with oligometastatic disease from esophagogastric adenocarcinoma (EGAC), although some studies suggest a more favorable survival. We analyzed the outcome of oligometastatic EGAC receiving FLOT chemotherapy followed by surgery. METHODS: The data of patients with either pre-therapeutic, post-neoadjuvant or intraoperative clinical diagnosis of oligometastatic EGAC were extracted from a prospective database of the 2009-2018 treatment period. 48 consecutive patients were identified with oligometastatic disease, who underwent perioperative chemotherapy plus surgery. We retrospectively analyzed surgical outcome and overall survival. RESULTS: The overall 5-year survival was 18%. 12 patients (25%) with pre-therapeutic oligometastatic EGAC, who had no histologic vital tumor evidence of metastases after surgery had a survival rate of 48% compared to an 11% 5-year survival rate of 36 patients (75%), who had histologic vital tumor metastatic evidence after FLOT chemotherapy and surgical resection (p = 0.012). The survival rates after R0, R1 and R2 (non-resected metastases) resection were 21% (n = 33), 0% (n = 4) and 17% (n = 11), respectively (p = 0.273). CONCLUSION: Oligometastatic EGAC is associated with poor overall survival even after complete resection of all tumor manifestations. The subgroup of patients with a complete histologic response of metastatic lesions to neoadjuvant FLOT shows 5-year survival rates similar to non-metastatic EGAC. Trial registration Not applicable.


Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/cirugía , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Esofágicas/cirugía , Terapia Neoadyuvante/métodos , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/cirugía , Adenocarcinoma/mortalidad , Adenocarcinoma/patología , Neoplasias Esofágicas/mortalidad , Neoplasias Esofágicas/patología , Unión Esofagogástrica , Femenino , Fluorouracilo/administración & dosificación , Humanos , Leucovorina/administración & dosificación , Masculino , Compuestos Organoplatinos/administración & dosificación , Oxaliplatino , Estudios Retrospectivos , Neoplasias Gástricas/mortalidad , Neoplasias Gástricas/patología , Tasa de Supervivencia , Taxoides/administración & dosificación , Resultado del Tratamiento
19.
Zentralbl Chir ; 146(6): 547-551, 2021 Dec.
Artículo en Alemán | MEDLINE | ID: mdl-33285577

RESUMEN

Since the introduction of robot-assisted surgery, increasingly complex operations have been performed with this technique. Robot-assisted operations are also of increasing importance in hepatobiliary surgery. With articulated and scaled movements in a three-dimensional surgical field, permit precise preparation, as is needed for major hepatic resection. This video demonstrates the feasibility and precision of completely robotic surgery in right hemihepatectomy in hepatocellular carcinoma (HCC) of segments V - VIII in non-alcoholic steatohepatitis (NASH). The patient was 72 years old for the operation, with concomitant marked metabolic syndrome.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Robótica , Anciano , Carcinoma Hepatocelular/cirugía , Hepatectomía , Humanos , Neoplasias Hepáticas/cirugía
20.
Ann Surg ; 272(5): 690-695, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-32657920

RESUMEN

OBJECTIVE: The aim of this study was to compare silicone-banded sleeve gastrectomy (BSG) to nonbanded sleeve gastrectomy (SG) regarding weight loss, obesity-related comorbidities, and complications. SUMMARY BACKGROUND DATA: As a primary bariatric procedure, SG leads to excellent weight loss, yet weight regain is a relevant issue in mid- to long-term follow-up. Retrospective analyses suggest that banding a sleeve using a silicone ring may decrease weight regain and improve weight loss. METHODS: The banded versus nonbanded sleeve gastrectomy single-center, randomized controlled trial was conducted from January 2015 to August 2019. The primary endpoint was defined as excess weight loss 3 years after surgery. Secondary endpoints included the surgery's impact on obesity-related comorbidities, quality of life, and complications. The study was registered under DRKS00007729. RESULTS: Among 94 patients randomized, 97% completed 3-year follow-up. Mean initial body mass index was 50.9 kg/m [95% confidence interval (CI), 49.6-52.2]. Mean adjusted excess weight loss 3 years after SG amounted to 62.3% (95% CI, 56.2-68.5) and 73.9% ( 95% CI, 67.8-80.0) after BSG (difference 11.6%, P = 0.0073). Remission of type 2 diabetes occurred in 66.7% (4/6) after SG and in 91.0% (10/11) following BSG (P = 0.21). Three years after surgery, ring implantation correlated with decreased frequency of symptomatic reflux episodes (P = 0.01) but increased frequency of regurgitation (P = 0.03). The rate of major complications was not different between the study groups (BSG, n = 3; SG, n = 2; P = 0.63). Quality of life was better following BSG (P = 0.001). CONCLUSIONS: BSG provided better weight loss than nonbanded SG 3 years after surgery. Regurgitation was the main clinically relevant negative effect after BSG.


Asunto(s)
Gastrectomía/métodos , Obesidad Mórbida/cirugía , Adulto , Comorbilidad , Femenino , Estudios de Seguimiento , Alemania , Humanos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias , Calidad de Vida , Siliconas
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