RESUMO
BACKGROUND: Data on perioperative chemotherapy in resectable pancreatic ductal adenocarcinoma (rPDAC) are limited. NEONAX examined perioperative or adjuvant chemotherapy with gemcitabine plus nab-paclitaxel in rPDAC (National Comprehensive Cancer Network criteria). PATIENTS AND METHODS: NEONAX is a prospective, randomized phase II trial with two independent experimental arms. One hundred twenty-seven rPDAC patients in 22 German centers were randomized 1 : 1 to perioperative (two pre-operative and four post-operative cycles, arm A) or adjuvant (six cycles, arm B) gemcitabine (1000 mg/m2) and nab-paclitaxel (125 mg/m2) on days 1, 8 and 15 of a 28-day cycle. RESULTS: The primary endpoint was disease-free survival (DFS) at 18 months in the modified intention-to-treat (ITT) population [R0/R1-resected patients who started neoadjuvant chemotherapy (CTX) (A) or adjuvant CTX (B)]. The pre-defined DFS rate of 55% at 18 months was not reached in both arms [A: 33.3% (95% confidence interval [CI] 18.5% to 48.1%), B: 41.4% (95% CI 20.7% to 62.0%)]. Ninety percent of patients in arm A completed neoadjuvant treatment, and 42% of patients in arm B started adjuvant chemotherapy. R0 resection rate was 88% (arm A) and 67% (arm B), respectively. Median overall survival (mOS) (ITT population) as a secondary endpoint was 25.5 months (95% CI 19.7-29.7 months) in arm A and 16.7 months (95% CI 11.6-22.2 months) in the upfront surgery arm. This difference corresponds to a median DFS (mDFS) (ITT) of 11.5 months (95% CI 8.8-14.5 months) in arm A and 5.9 months (95% CI 3.6-11.5 months) in arm B. Treatment was safe and well tolerable in both arms. CONCLUSIONS: The primary endpoint, DFS rate of 55% at 18 months (mITT population), was not reached in either arm of the trial and numerically favored the upfront surgery arm B. mOS (ITT population), a secondary endpoint, numerically favored the neoadjuvant arm A [25.5 months (95% CI 19.7-29.7months); arm B 16.7 months (95% CI 11.6-22.2 months)]. There was a difference in chemotherapy exposure with 90% of patients in arm A completing pre-operative chemotherapy and 58% of patients starting adjuvant chemotherapy in arm B. Neoadjuvant/perioperative treatment is a novel option for patients with resectable PDAC. However, the optimal treatment regimen has yet to be defined. The trial is registered with ClinicalTrials.gov (NCT02047513) and the European Clinical Trials Database (EudraCT 2013-005559-34).
Assuntos
Gencitabina , Neoplasias Pancreáticas , Humanos , Desoxicitidina , Estudos Prospectivos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/cirurgia , Neoplasias Pancreáticas/patologia , Albuminas , Paclitaxel , Terapia Neoadjuvante , Adjuvantes Imunológicos/uso terapêutico , Neoplasias PancreáticasRESUMO
PURPOSE: To develop nomograms for pre- and early-postoperative risk assessment of patients undergoing pancreatic head resection. METHODS: Clinical data from 956 patients were collected in a prospectively maintained database. A test (n = 772) and a validation cohort (n = 184) were randomly generated. Uni- and multi-variate analysis and nomogram construction were performed to predict severe postoperative complications (Clavien-Dindo Grades III-V) in the test cohort. External validation was performed with the validation cohort. RESULTS: We identified ASA score, indication for surgery, body mass index (BMI), preoperative white blood cell (WBC) count, and preoperative alkaline phosphatase as preoperative factors associated with an increased perioperative risk for complications. Additionally to ASA score, BMI, indication for surgery, and the preoperative alkaline phosphatase, the following postoperative parameters were identified as risk factors in the early postoperative setting: the need for intraoperative blood transfusion, operation time, maximum WBC on postoperative day (POD) 1-3, and maximum serum amylase on POD 1-3. Two nomograms were developed on the basis of these risk factors and showed accurate risk estimation for severe postoperative complications (ROC-AUC-values for Grades III-V-preoperative nomogram: 0.673 (95%, CI: 0.626-0.721); postoperative nomogram: 0.734 (95%, CI: 0.691-0.778); each p ≤ 0.001). Validation yielded ROC-AUC-values for Grades III-V-preoperative nomogram of 0.676 (95%, CI: 0.586-0.766) and postoperative nomogram of 0.677 (95%, CI: 0.591-0.762); each p = 0.001. CONCLUSION: Easy-to-use nomograms for risk estimation in the pre- and early-postoperative setting were developed. Accurate risk estimation can support the decisional process, especially for IPMN-patients with an increased perioperative risk.
Assuntos
Fosfatase Alcalina , Nomogramas , Humanos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Fatores de RiscoRESUMO
BACKGROUND: The impact of body compositions on surgical results is controversially discussed. This study examined whether visceral obesity, sarcopenia or sarcopenic obesity influence the outcome after hepatic resections of synchronous colorectal liver metastases. METHODS: Ninety-four consecutive patients with primary hepatic resections of synchronous colorectal metastases were identified from a single center database between January 2013 and August 2018. Patient characteristics and 30-day morbidity were retrospectively analyzed. Body fat and skeletal muscle were calculated by planimetry from single-slice CT images at the level of L3. RESULTS: Fifty-nine patients (62.8%) underwent minor hepatectomies, and 35 patients underwent major resections (37.2%). Postoperative complications occurred in 60 patients (62.8%) including 35 patients with major complications (Clavien-Dindo grade III-V). The mortality was nil at 30 days and 2.1% at 90 days. The body mass index showed no influence on postoperative outcomes (p = 1.0). Visceral obesity was found in 66 patients (70.2%) and was significantly associated with overall and major complication rates (p = .002, p = .012, respectively). Sarcopenia was observed in 34 patients (36.2%) without a significant impact on morbidity (p = .461), however, with longer hospital stay. Sarcopenic obesity was found in 18 patients (19.1%) and was significantly associated with postoperative complications (p = .014). Visceral obesity, sarcopenia and sarcopenic obesity were all identified as significant risk factors for overall postoperative complications. CONCLUSION: Visceral obesity, sarcopenic obesity and sarcopenia are independent risk factors for overall complications after resections of CRLM. Early recognition of extremes in body compositions could prompt to perioperative interventions and thus improve postoperative outcomes.
Assuntos
Neoplasias Colorretais , Obesidade Abdominal , Sarcopenia , Neoplasias Colorretais/complicações , Neoplasias Colorretais/cirurgia , Hepatectomia/efeitos adversos , Humanos , Fígado , Obesidade/complicações , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Sarcopenia/complicações , Sarcopenia/epidemiologia , Resultado do TratamentoAssuntos
Biomarcadores Tumorais/genética , Carcinoma Ductal Pancreático/genética , DNA Tumoral Circulante/sangue , Recidiva Local de Neoplasia/diagnóstico , Neoplasias Pancreáticas/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/sangue , Carcinoma Ductal Pancreático/sangue , Carcinoma Ductal Pancreático/mortalidade , Carcinoma Ductal Pancreático/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/sangue , Recidiva Local de Neoplasia/genética , Neoplasias Pancreáticas/sangue , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/cirurgia , Estudos Prospectivos , Proteínas Proto-Oncogênicas p21(ras)/sangueRESUMO
INTRODUCTION: Pancreatic trauma (PT) involving the main pancreatic duct is rare, but represents a challenging clinical problem with relevant morbidity and mortality. It is generally classified according to the American Association for the Surgery of Trauma (AAST) and often presents as concomitant injury in blunt or penetrating abdominal trauma. Diagnosis may be delayed because of a lack of clinical or radiological manifestation. Treatment options for main pancreatic duct injuries comprise highly complex surgical procedures. PATIENTS AND METHODS: We retrospectively analyzed clinical data from 12 patients who underwent surgery in two tertiary centers in Germany during 2003-2016 for grade III-V PT with affection of the main pancreatic duct, according to the AAST classification. RESULTS: The median age was 23 (range: 7-44) years. In nine patients blunt abdominal trauma was the reason for PT, whereas penetrating trauma only occurred in three patients. MRI outperformed classical trauma CT imaging with regard to detection of duct involvement. Complex procedures as i.e. an emergency pancreatic head resection, distal pancreatectomy or parenchyma sparing pancreatogastrostomy were performed. Compared to elective pancreatic surgery the complication rate in the emergency setting was higher. Yet, parenchyma-sparing procedures demonstrated safety. CONCLUSIONS: Often extension of diagnostics including MRI and/or ERP at an early stage is necessary to guide clinical decision-making. If, due to main duct injuries, surgical therapy for PT is required, we suggest consideration of an organ preservative pancreatogastrostomy in grade III/IV trauma of the pancreatic body or tail.
Assuntos
Traumatismos Abdominais , Ferimentos não Penetrantes , Traumatismos Abdominais/diagnóstico por imagem , Traumatismos Abdominais/cirurgia , Adulto , Alemanha , Humanos , Pâncreas/diagnóstico por imagem , Pâncreas/lesões , Pâncreas/cirurgia , Pancreatectomia , Estudos Retrospectivos , Resultado do Tratamento , Ferimentos não Penetrantes/diagnóstico por imagem , Ferimentos não Penetrantes/cirurgia , Adulto JovemRESUMO
BACKGROUND: Many techniques have been developed to prevent postoperative pancreatic fistula (POPF) after distal pancreatectomy, but POPF rates remain high. The aim of our study was to analyze POPF occurrence after closure of the pancreatic remnant by different operative techniques. METHODS: Between 2006 and 2017, 284 patients underwent distal pancreatectomy in our institution. For subgroup analysis the patients were divided into hand-sewn (n = 201) and stapler closure (n = 52) groups. The hand-sewn closure was performed in three different ways (fishmouth-technique, n = 27; interrupted transpancreatic U-suture technique, n = 77; common interrupted suture, n = 97). All other techniques were summarized in a separate group (n = 31). Results were gained by analysis of our prospective pancreatic database. RESULTS: The median age was 63 (range 23-88) years. 74 of 284 patients (26%) were operated with spleen preservation (similar rates in subgroups). ASA-classes, median BMI as well as frequencies of malignant diseases, chronic pancreatitis, alcohol and nicotine abuse were also comparable in the subgroups. Neither the rates of overall POPF (fishmouth-technique 30%, common interrupted suture 40%, stapler closure 33% and interrupted U-suture 38%) nor the rates of POPF grades B and C showed significant differences in the subgroups. However is shown to be associated with pancreatic function and parenchymal texture. CONCLUSION: In our experience the technique of pancreatic stump closure after distal resection did not influence postoperative pancreatic fistula rate. As a consequence patient specific reasons rather than surgical techniques may be responsible for POPF formation after distal pancreatectomy.
Assuntos
Pâncreas/cirurgia , Pancreatectomia/métodos , Fístula Pancreática/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Técnicas de Fechamento de Ferimentos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto JovemRESUMO
Background: This study evaluated the outcome and survival of patients with radiologically suspected intraductal papillary mucinous neoplasms (IPMNs). Methods: IPMN management was reviewed according to Fukuoka risk factors and IPMN localization, differentiating main-duct (MD), mixed-type (MT) and branch-duct (BD) IPMNs. Perioperative results were compared with those of patients undergoing resection of pancreatic ductal adenocarcinoma (PDAC) over the same interval (2010-2014). Overall (OS) and disease-specific (DSS) survival rates were calculated and subgroups compared. Results: Of 142 patients with IPMNs, 26 had MD-IPMN, eight had MT-IPMN and 108 had BD-IPMN. Some 74 per cent of patients with MD- and MT-IPMN were managed by primary resection, whereas this was used in only 27·8 per cent of those with BD-IPMN. The risk of secondary resection and malignant transformation for BD-IPMNs smaller than 20 mm was 8 and 2 per cent respectively during follow-up. Pancreatic head resection of IPMNs was associated with an increased risk of postoperative pancreatic fistula grade B/C compared with resection of PDAC (12 of 33 (36 per cent) versus 41 of 221 (18·6 per cent) respectively; P = 0·010), and greater morbidity and mortality (Clavien-Dindo grade III: 15 of 33 (45 per cent) versus 56 of 221 (25·3 per cent) respectively; grade IV: 1 (3 per cent) versus 7 (3·2 per cent); grade V: 2 (6 per cent) versus 2 (0·9 per cent); P = 0·008). Five-year OS and DSS rates in patients with MD-IPMN were worse than those for MT- and BD-IPMN (OS: 44, 86 and 97·4 per cent respectively, P < 0·001; DSS: 60, 100 and 98·6 per cent; P < 0·001). Patients with invasive IPMN had worse OS and DSS rates than those with non-invasive dysplasia (OS: IPMN-carcinoma (10 patients) 33 per cent, high-grade dysplasia 100 per cent, intermediate-grade dysplasia 63 per cent, low grade-dysplasia 100 per cent, P < 0·001; DSS: IPMN-carcinoma 43 per cent, all grades of dysplasia 100 per cent, P < 0·001). Patients with high-risk stigmata had poorer survival than those without risk factors (OS: high-risk stigmata (35 patients) 55 per cent, worrisome features (31) 95 per cent, no risk factors (76) 100 per cent, P < 0·001; DSS: 71, 100 and 100 per cent respectively, P < 0·001). Conclusion: The risk of malignant transformation was very low for BD-IPMNs, but the development of high-risk stigmata was associated with disease-specific mortality. Patients with IPMN had greater morbidity after resection than those having resection of PDAC.
Assuntos
Pancreatectomia , Neoplasias Intraductais Pancreáticas , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pâncreas/cirurgia , Pancreatectomia/efeitos adversos , Pancreatectomia/mortalidade , Neoplasias Intraductais Pancreáticas/mortalidade , Neoplasias Intraductais Pancreáticas/cirurgia , Complicações Pós-Operatórias , Fatores de Risco , Resultado do TratamentoRESUMO
INTRODUCTION: Total mesorectal excision (TME) is the international standard for rectal cancer surgery. In addition to laparoscopic TME (lapTME), transanal TME (taTME) was developed in recent years to reduce the rate of incomplete TME, conversion to open surgery and postoperative functional impairment. Despite limited evidence, this technique is becoming increasingly more popular and is already routinely used by many hospitals for rectal cancer in varying tumor level locations. The aim of this review was to evaluate the taTME compared to anterior rectal resection with lapTME as the standard of care in rectal cancer surgery based on currently available evidence. METHOD: The databases PubMed and Medline were systematically searched for publications on transanal total mesorectal excision (taTME) and transanal minimally invasive surgery (TAMIS). Relevant studies were selected and further research based on the reference lists was undertaken. RESULTS: A total of 16 studies analyzing 3782 patients were identified. The taTME does not lead to a higher rate of complete TME-resected specimens compared to the standard procedure. So far, superiority could not be demonstrated for complication rates or for functional or oncological results. Serious complications secondary to dissection in incorrect planes were observed. The anastomotic level generally seems to be closer to the sphincter after taTME versus anterior lapTME. CONCLUSION: Considering current evidence, taTME failed to show superiority compared to conventional anterior lapTME. Although taTME has some potential advantages, it carries substantial risks. If performed outside of clinical trials, it should therefore only be used in carefully selected patients with a high possibility of conversion, following adequate patient informed consent and after intense and systematic training of the surgeon.
Assuntos
Laparoscopia , Neoplasias Retais , Cirurgia Endoscópica Transanal , Humanos , Complicações Pós-Operatórias , Neoplasias Retais/cirurgia , RetoRESUMO
BACKGROUND: The surgical treatment of obesity in Germany is a rapidly developing field which is strictly controlled by national guidelines. OBJECTIVE: Depiction of the burden on obesity centers by the exponential increase in numbers of patients following bariatric treatment. METHODS: In a retrospective study the numbers of outpatients at this university obesity center (founded 2007) were descriptively analyzed. Outpatient visits were documented annually and divided into two groups: primary visit and follow-up visit. The frequency of bariatric operations as well as their acceptance/cost coverage by health insurances were evaluated. RESULTS: Overall 318 patients were seen in 2007: 156 primary and 162 follow-up visits. The health insurance rejection rate for cost coverage was 16.8%. There were 1691 outpatient visits in 2016 (2016 vs. 2007: +532%), of which 487 (+312%) were primary and 1204 (+743%) follow-up visits. The health insurance rejection rate dropped to 1.8%, while the frequency of operations increased nearly tenfold. CONCLUSION: With the increasing acceptance of bariatric surgery, a relatively low number of specialized centers have to deal with an exponentially rising follow-up frequency. In consideration of the extent of the obesity epidemic an adequate follow-up constitutes a socioeconomic problem, which can only be solved in an interdisciplinary setting under structural integration.
Assuntos
Assistência ao Convalescente , Cirurgia Bariátrica , Obesidade Mórbida , Alemanha , Humanos , Obesidade Mórbida/cirurgia , Estudos RetrospectivosRESUMO
BACKGROUND: The incidence of intrahepatic cholangiocarcinoma (ICC) is increasing worldwide. Surgical resection is the only curative treatment option. AIM OF THE STUDY: This study analyzed the prognostic factors after resection of ICC. MATERIAL AND METHODS: A total of 84 patients were surgically treated under potentially curative intent. Perihilar and distal cholangiocarcinomas were excluded. The 5year survival was analyzed with respect to tumor stage (TNM), number of lesions, complete surgical resection (R0), peritoneal carcinosis and postoperative complications. RESULTS: The 5year survival was 27% and 77% of patients underwent R0 resections. In the univariate analysis a T stage >2, an N+ situation or an R+ resection as well as peritoneal and multilocular intrahepatic spread were associated with a poorer prognosis. Postoperative complications also negatively influenced survival. On multivariate analysis the absence of peritoneal spread, node-negative tumor stages, singular hepatic lesions and a low T stage as well as the absence of complications were associated with improved survival. DISCUSSION: The prognosis of ICC is poor even after successful surgical resection. Well-known tumor characteristics such as TNM are relevant prognostic factors. Surgical resection is accompanied by postoperative complications (most frequently biliary), which negatively influence survival. Adjuvant strategies are urgently needed to improve long-term survival even after complete surgical resection.
Assuntos
Neoplasias dos Ductos Biliares , Ductos Biliares Intra-Hepáticos , Colangiocarcinoma , Neoplasias dos Ductos Biliares/cirurgia , Colangiocarcinoma/cirurgia , Hepatectomia , Humanos , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do TratamentoRESUMO
BACKGROUND: Intra-abdominal abscesses [IAAs] are common life-threatening complications in patients with Crohn's disease [CD]. In addition to interventional drainage and surgical therapy, empirical antibiotic therapy represents a cornerstone of treatment, but contemporary data on microbial spectra and antimicrobial resistance are scarce. METHODS: We recruited 105 patients with CD and IAAs from nine German centres for a prospective registry in order to characterize the microbiological spectrum, resistance profiles, antibiotic therapy and outcome. RESULTS: In 92 of 105 patients, microbial investigations of abscess material revealed pathogenic microorganisms. A total of 174 pathogens were isolated, with a median of 2 pathogens per culture [range: 1-6]. Most frequently isolated pathogens were E. coli [45 patients], Streptococcus spp. [28 patients], Enterococci [27 patients], Candida [13 patients] and anaerobes [12 patients]. Resistance to third-generation cephalosporins, penicillins with beta-lactamase inhibitors and quinolones were observed in 51, 36 and 35 patients, respectively. Seven patients had multiple-drug-resistant bacteria. Thirty patients received inadequate empirical treatment, and this was more frequent in patients receiving steroids or immunosuppression [37%] than in patients without immunosuppression [10%: p = 0.001] and was associated with a longer hospital stay [21 days vs 13 days, p = 0.003]. CONCLUSION: Based on antimicrobial resistance profiles, we herein report a high rate of inadequate empirical first-line therapy for IAAs in CD, especially in patients receiving immunosuppression, and this is associated with prolonged hospitalization.
Assuntos
Abscesso Abdominal/tratamento farmacológico , Abscesso Abdominal/microbiologia , Antibacterianos/uso terapêutico , Doença de Crohn/complicações , Enterobacteriaceae/isolamento & purificação , Perfuração Intestinal/complicações , Adulto , Antibacterianos/farmacologia , Antifúngicos/uso terapêutico , Candida albicans/isolamento & purificação , Carbapenêmicos/uso terapêutico , Cefalosporinas/uso terapêutico , Doença de Crohn/tratamento farmacológico , Farmacorresistência Bacteriana Múltipla , Enterobacteriaceae/efeitos dos fármacos , Enterococcus/efeitos dos fármacos , Enterococcus/isolamento & purificação , Feminino , Alemanha , Humanos , Imunossupressores/uso terapêutico , Tempo de Internação , Levofloxacino/uso terapêutico , Masculino , Penicilinas/uso terapêutico , Estudos Prospectivos , Quinolonas/uso terapêutico , Sistema de Registros , Streptococcus/efeitos dos fármacos , Streptococcus/isolamento & purificação , Adulto Jovem , Inibidores de beta-Lactamases/uso terapêuticoRESUMO
Fibrosis is a major component of chronic cardiac allograft rejection. Although several cell types are able to produce collagen, resident (donor-derived) fibroblasts are mainly responsible for excessive production of extracellular matrix proteins. It is currently unclear which cells regulate production of connective tissue elements in allograft fibrosis and how basophils, as potential producers of profibrotic cytokines, are involved this process. We studied this question in a fully MHC-mismatched model of heart transplantation with transient depletion of CD4(+) T cells to largely prevent acute rejection. The model is characterized by myocardial infiltration of leukocytes and development of interstitial fibrosis and allograft vasculopathy. Using depletion of basophils, IL-4-deficient recipients and IL-4 receptor-deficient grafts, we showed that basophils and IL-4 play crucial roles in activation of fibroblasts and development of fibrotic organ remodeling. In the absence of CD4(+) T cells, basophils are the predominant source of IL-4 in the graft and contribute to expansion of myofibroblasts, interstitial deposition of collagen and development of allograft vasculopathy. Our results indicated that basophils trigger the production of various connective tissue elements by myofibroblasts. Basophil-derived IL-4 may be an attractive target for treatment of chronic allograft rejection.
Assuntos
Basófilos/imunologia , Rejeição de Enxerto/etiologia , Cardiopatias/etiologia , Transplante de Coração/efeitos adversos , Interleucina-4/fisiologia , Aloenxertos , Animais , Feminino , Fibrose/etiologia , Fibrose/patologia , Rejeição de Enxerto/patologia , Sobrevivência de Enxerto , Cardiopatias/patologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos KnockoutRESUMO
BACKGROUND: Liver metastases occur in 40-50 per cent of patients with colorectal cancer and determine long-term survival. The aim of this study was to examine the immunological architecture of colorectal liver metastases and its impact on patient survival. METHODS: Specimens from patients with colorectal liver metastases were stained with haematoxylin and eosin and Masson trichrome, immunostained for α-smooth muscle actin, CD4, CD45RO and CD8, and analysed by flow cytometry. In addition to histomorphological evaluation, immunohistochemically stained sections were analysed for cell numbers in the tumour area, infiltrative margin and distant liver stroma separately. These findings were correlated with clinical data and patient outcome. RESULTS: Tumour containment by a fibrotic capsule around liver metastases was observed in 37·8 per cent of 201 patients and was prognostic for improved survival (median (s.e.) survival 64 (6) and 31 (4) months for patients with capsule and no capsule respectively; P < 0·001) and independently led to higher R0 resection rates (P = 0·040). In multivariable analysis, CD45RO(+) cell infiltration at the peritumoral margin with low CD45RO(+) cell infiltration in the distant liver stroma (P = 0·001) and fibrotic capsule formation (P = 0·008) both independently prolonged patient survival. Using these two factors, a cellular immune score was designed and shown to stratify patient survival in test and validation samples (both P < 0·001). CONCLUSION: Fibrotic capsule formation and localized cell infiltration of colorectal liver metastases by CD45RO(+) cells were related to prolonged patient survival. Based on these immunological criteria a cellular immune score was developed to stratify patients according to prognosis.
Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias Colorretais , Neoplasias Hepáticas/imunologia , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Antígenos CD4/metabolismo , Antígenos CD8/metabolismo , Feminino , Fibrose/patologia , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Prognóstico , Medição de Risco/métodos , Microambiente Tumoral/imunologiaRESUMO
PURPOSE: To evaluate the extent to which MRE can be used as an observer-independent, objective imaging method for the diagnosis and evaluation of CD with respect to the detection of inflammatory changes of the small bowel and lymphadenopathy as diagnostic criterion and bowel distension as a quality criterion. MATERIALS AND METHODS: MRE scans of 84 patients (42 female, median age 37 years) were evaluated independently by 4 experienced radiologists. Analysis of inflammatory changes of the bowel wall, lymphadenopathy and adequate bowel distension was conducted separately for the jejunum, ileum and terminal ileum. The Kendall's W-test was used for the statistical comparison of concordance. RESULTS: In a total of 55 patients, inflammatory activity of the bowel wall was detected and MRE was found to have a high interobserver reproducibility concerning inflammatory changes of the intestinal wall (Kendall's W 0.527 - 0.823). Concerning lymphadenopathy (31 cases, 36.9 %), a low to moderate consensus could be shown with a Kendall's W value of 0.402 - 0.505. For the assessment of adequate bowel distension, a moderate concordance between the operators could be found (Kendall's W 0.497 - 0.581). CONCLUSION: MRE has proven high interobserver agreement with respect to the diagnosis of inflammatory disease activity of the bowel as a diagnostic criterion in patients with CD. Concerning adequate bowel distension as a quality criterion of the examination itself and lymphadenopathy as a diagnostic criterion, moderate interobserver agreement could be found. This is thought to have a rather small effect on the diagnostic significance and conclusiveness of the method in the daily routine. KEY POINTS: ⶠMR enterography as observer independent diagnostic procedure in patients with Chron's Disease. ⶠHighest interobserver concordance for the criterion of inflammatory bowel wall affection. ⶠModerate interobserver concordance for lymphadenopathy and bowel distension.
Assuntos
Doença de Crohn/diagnóstico , Íleo/patologia , Interpretação de Imagem Assistida por Computador/métodos , Jejuno/patologia , Imageamento por Ressonância Magnética/métodos , Adulto , Meios de Contraste , Diagnóstico Diferencial , Feminino , Seguimentos , Gadolínio DTPA , Humanos , Linfonodos/patologia , Doenças Linfáticas/diagnóstico , Masculino , Variações Dependentes do Observador , Estudos Prospectivos , Sensibilidade e EspecificidadeRESUMO
The innate receptor "triggering-receptor-expressed-on-myeloid-cells-1" (TREM-1) enhances downstream signaling of "pattern recognition receptor" (PRR) molecules implicated in inflammatory responses. However the mechanistic role of TREM-1 in chronic heart rejection has yet to be elucidated. We examined the effect of TREM-1(+) antigen-presenting cells (APC) on alloreactive CD4(+) lymphocytes. Bm12 donor hearts were transplanted into wild-type MHC-class-II-mismatched C57BL/6J recipient mice. Progressive allograft rejection of bm12-donor hearts with decreased organ function, severe vasculopathy and allograft fibrosis was evident within 4 weeks. TREM-1(+) CD11b(+) MHC-II(+) F4/80(+) CCR2(+) APC and IFNγ-producing CD4(+) cells were detected during chronic rejection. Peptide inhibition of TREM-1 attenuated graft vasculopathy, reduced graft-infiltrating leukocytes and prolonged allograft survival, while being accompanied by sustained low levels of CD4(+) and CD8(+) cell infiltration. Remarkably, temporary inhibition of TREM-1 during early immune activation was sufficient for long-term allograft survival. Mechanistically, TREM-1 inhibition leads to reduced differentiation and proliferation of IFNγ-producing Th1 cells. In conclusion, TREM-1 influences chronic heart rejection by regulating the infiltration and differentiation of CD4(+) lymphocytes.
Assuntos
Linfócitos T CD4-Positivos/imunologia , Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto/imunologia , Transplante de Coração/imunologia , Ativação Linfocitária/imunologia , Glicoproteínas de Membrana/antagonistas & inibidores , Receptores Imunológicos/antagonistas & inibidores , Animais , Células Apresentadoras de Antígenos/imunologia , Técnicas de Cocultura , Modelos Animais de Doenças , Feminino , Citometria de Fluxo , Regulação da Expressão Gênica , Rejeição de Enxerto/genética , Rejeição de Enxerto/imunologia , Sobrevivência de Enxerto/efeitos dos fármacos , Sobrevivência de Enxerto/genética , Imuno-Histoquímica , Glicoproteínas de Membrana/biossíntese , Glicoproteínas de Membrana/genética , Camundongos , Camundongos Endogâmicos C57BL , RNA/genética , Reação em Cadeia da Polimerase em Tempo Real , Receptores Imunológicos/biossíntese , Receptores Imunológicos/genética , Transdução de Sinais/imunologia , Transplante Homólogo , Receptor Gatilho 1 Expresso em Células MieloidesRESUMO
PURPOSE: To evaluate the extent to which MRE can be used as an observer-independent, objective imaging method for the diagnosis and evaluation of CD with respect to the detection of inflammatory changes of the small bowel and lymphadenopathy as diagnostic criterion and bowel distension as a quality criterion. MATERIALS AND METHODS: MRE scans of 84 patients (42 female, median age 37 years) were evaluated independently by 4 experienced radiologists. Analysis of inflammatory changes of the bowel wall, lymphadenopathy and adequate bowel distension was conducted separately for the jejunum, ileum and terminal ileum. The Kendall's W-test was used for the statistical comparison of concordance. RESULTS: In a total of 55 patients, inflammatory activity of the bowel wall was detected and MRE was found to have a high interobserver reproducibility concerning inflammatory changes of the intestinal wall (Kendall's W 0.527 0.823). Concerning lymphadenopathy (31 cases, 36.9 %), a low to moderate consensus could be shown with a Kendall's W value of 0.402 0.505. For the assessment of adequate bowel distension, a moderate concordance between the operators could be found (Kendall's W 0.497 0.581). CONCLUSION: MRE has proven high interobserver agreement with respect to the diagnosis of inflammatory disease activity of the bowel as a diagnostic criterion in patients with CD. Concerning adequate bowel distension as a quality criterion of the examination itself and lymphadenopathy as a diagnostic criterion, moderate interobserver agreement could be found. This is thought to have a rather small effect on the diagnostic significance and conclusiveness of the method in the daily routine.
Assuntos
Doença de Crohn/diagnóstico , Mucosa Intestinal/patologia , Linfonodos/patologia , Imageamento por Ressonância Magnética/métodos , Adulto , Meios de Contraste , Doença de Crohn/patologia , Feminino , Gadolínio DTPA , Humanos , Íleo/patologia , Aumento da Imagem/métodos , Jejuno/patologia , Masculino , Variações Dependentes do Observador , Sensibilidade e EspecificidadeRESUMO
Techniques for biliodigestive anastomoses are a frequent indication in primary surgical interventions. Moreover, they are required to manage secondary complications of hepatobiliary surgery. Evidence for the management of complications following biliodigestive anastomoses is low. Biliodigestive anastomoses can be performed as hepaticojejunostomy, hepatojejunostomy/portoenterostomy and hepaticoduodenostomy using running or single stitch suture techniques. Complication management in the hands of experienced hepatopancreatobiliary surgeons should consider a time delay to the primary operation and an interdisciplinary surgical and/or endoscopic or radiologic interventional approach. The therapy may be protracted and requires repeated critical reflection of the particular complication.