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BACKGROUND: This is the first randomized trial to evaluate the efficacy of intraoperative cholangiography (IOC) and magnetic resonance cholangiopancreatography (MRCP) in patients with suspected CBDS. METHODS: This unblinded, multicenter RCT was conducted at five swiss hospitals. Eligibility criteria were suspected CBDS. Patients were randomized to IOC and laparoscopic cholecystectomy (LC), followed by endoscopic retrograde cholangiopancreatography (ERCP) if needed, or MRCP followed by ERCP if needed, and LC. Primary outcome was length of stay (LOS), secondary outcomes were cost, stone detection, and complication rates. RESULTS: 122 Patients were randomised to the IOC Group (63) or the MRCP group (59). Median LOS for the IOC and the MRCP groups were 4 days IQR [3, 6] and [4, 6], with an estimated increase of LOS of 1.2 days in the MRCP group (p = 0.0799) in the linear model. Median cost in the IOC and MRCP groups were 10 473 Swiss Francs (CHF) and 10 801 CHF, respectively (p = 0.694). CBDS were found in 24 and 12 patients in the IOC and the MRCP groups, respectively (p = 0.0387). The complication rate did not differ between both groups. CONCLUSION: There is equipoise between both pathways. IOC has a significantly higher diagnostic yield than MRCP. TRIAL REGISTRATION: Clinicaltrials.gov identifier NCT02351492: Radiological Investigation of Bile Duct Obstruction (RIBO).
Assuntos
Colecistectomia Laparoscópica , Cálculos Biliares , Humanos , Estudos Retrospectivos , Colangiografia , Cálculos Biliares/diagnóstico por imagem , Cálculos Biliares/cirurgia , Cálculos Biliares/complicações , Colecistectomia Laparoscópica/efeitos adversos , Colangiopancreatografia Retrógrada Endoscópica/efeitos adversos , Espectroscopia de Ressonância Magnética , Ducto ColédocoRESUMO
BACKGROUND: Optimal resource utilization in high-cost environments like operating theatres is fundamental in today's cost constrained health care systems. Interruptions of the surgical workflow, i.e. microcomplications (MC), lead to prolonged procedure times and higher costs and can be indicative of surgical mistakes. Reducing MC can improve operating room efficiency and prevent intraoperative complications. We, therefore, aimed to evaluate the impact of a high-resolution standardized laparoscopic cholecystectomy protocol (HRSL) on operative time and intraoperative interruptions in a teaching hospital. METHODS: HRSL consisted of a detailed stepwise protocol for the procedure, supported by a teaching video, both to be reviewed as mandatory preparation by each team member before surgery. Audio-video records of laparoscopic cholecystectomies were reviewed regarding type, frequency and duration of MC before and after implementation of HRSL. RESULTS: Thirty-nine (20 control and 19 HRSL) audio-video records of laparoscopic cholecystectomies with a total duration of 51.36 h (28.92 pre 22.44 post) were reviewed. The majority of operations (86%) were performed by teams who had completed less than 10 procedures together previously. Communication-related interruptions and instrument changes accounted for the majority of MC. Median frequency and duration of MC were 95 events/h and 15.6 min/h, respectively, of surgery pre-intervention. With HRSL this was reduced to 76 events/h and 10.6 min/h of operating. In multivariable analysis, HRSL was an independent predictor for shorter delay and lower frequency of MC [percentage decrease 27% (95% CI 18-35%), resp. 30% (95% CI 19-40%)]. Procedure-related risk factors for the longer delay due to MC in multivariable analysis were less experience of the surgeon and intraoperative adhesiolysis. CONCLUSIONS: HRSL is effective in reducing delays due to MC in a teaching institution with limited team experience. These findings should be tested in larger potentially cluster-randomized controlled trials. The trial has been registered with clinicaltrials.gov: NCT03329859.
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Colecistectomia Laparoscópica , Complicações Intraoperatórias/prevenção & controle , Erros Médicos/prevenção & controle , Salas Cirúrgicas/organização & administração , Gestão da Qualidade Total/métodos , Fluxo de Trabalho , Colecistectomia Laparoscópica/efeitos adversos , Colecistectomia Laparoscópica/economia , Colecistectomia Laparoscópica/métodos , Colecistectomia Laparoscópica/normas , Cirurgia Geral/educação , Humanos , Capacitação em Serviço/métodos , Duração da Cirurgia , SuíçaRESUMO
OBJECTIVES: To assess the predictive value of serum trypsin and trypsinogen activation peptide (TAP) for the severity of AP through a single center cohort study as well as a systematic review of the current literature. METHODS: A literature search was conducted using Medline (PubMed), EMBASE and the Cochrane Central Register. A total of 142 patients with acute pancreatitis (AP) were included in the cohort study and parameters of the revised Atlanta criteria of 2012 and the APACHE II were assessed. RESULTS: The review showed promising results for the predictive value of serum trypsinogen-2 but conflicting results for serum TAP and trypsin. In the cohort study, patients were observed for 4 days after diagnosis of AP; 9 patients had severe AP, 35 patients had moderate AP and 81 patients had mild AP. The ratio of the geometric mean of severe vs. mild AP for trypsin was 0.72 (95% CI: 0.51-1.00), p = 0.053 and, for TAP, 0.74 (95% CI: 0.54-1.01), p = 0.055, respectively. CONCLUSIONS: The cohort study showed an inverse correlation of serum levels of TAP and trypsin with severity of AP. Serum TAP and trypsin have an inferior predictive value of severity of AP compared to the clinical APACHE II score.
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BACKGROUND: Closed loop ileus caused by entrapment of bowel in a defect of the broad ligament is a rarity. Only a few cases have been reported in the literature. CASE SUMMARY: We present the case of a 44-year-old, healthy patient with no prior history of abdominal surgery who developed a closed loop ileus due to an internal hernia secondary to a defect in the right broad ligament. She first presented to the emergency department with diarrhea and vomiting. As she had had no previous abdominal surgery, she was diagnosed with probable gastroenteritis and discharged. The patient subsequently returned to the emergency department due to a lack of improvement in her symptoms. Blood tests showed an elevated white blood cell count and a closed loop ileus was diagnosed on an abdominal computer tomography scan. Diagnostic laparoscopy revealed an internal hernia entrapped in a 2 cm large defect in the right broad ligament. The hernia was reduced and the ligament defect was closed using a running, barbed suture. CONCLUSION: Bowel incarceration through an internal hernia may present with misleading symptoms and laparoscopy may reveal unexpected findings.
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Stromal infiltration is associated with poor prognosis in human colon cancers. However, the high heterogeneity of human tumor-associated stromal cells (TASCs) hampers a clear identification of specific markers of prognostic relevance. To address these issues, we established short-term cultures of TASCs and matched healthy mucosa-associated stromal cells (MASCs) from human primary colon cancers and, upon characterization of their phenotypic and functional profiles in vitro and in vivo, we identified differentially expressed markers by proteomic analysis and evaluated their prognostic significance. TASCs were characterized by higher proliferation and differentiation potential, and enhanced expression of mesenchymal stem cell markers, as compared to MASCs. TASC triggered epithelial-mesenchymal transition (EMT) in tumor cells in vitro and promoted their metastatic spread in vivo, as assessed in an orthotopic mouse model. Proteomic analysis of matched TASCs and MASCs identified a panel of markers preferentially expressed in TASCs. The expression of genes encoding two of them, calponin 1 (CNN1) and tropomyosin beta chain isoform 2 (TPM2), was significantly associated with poor outcome in independent databases and outperformed the prognostic significance of currently proposed TASC markers. The newly identified markers may improve prognostication of primary colon cancers and identification of patients at risk.
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A 47-year-old patient presented at our emergency department with acute epigastric pain. A thoracic X-ray showed a partially intrathoracic stomach as well as bowel left sided. A following computed tomography scan diagnosed a diaphragmatic hernia. In the patient's history, 20 years ago a serious car accident was reported as the presumable traumatic origin. Intraoperatively, the diaphragmatic hernia was repaired with a direct suture and mesh augmentation. The rest of the abdomen was clear. In a thoracic X-ray following chest tube removal, herniated small bowel appeared intrathoracally on the right. Relaparotomy showed an extensive diaphragmatic hernia with parts of the liver, small bowel and colon in the right thoracic cavity. Only a partial direct repair was possible, an inlay mesh repair was performed. The further recovery was uneventful. Bilateral delayed traumatic diaphragmatic hernias are extremely rare, but with a suggestive trauma history thorough intraoperative exploration of the contralateral side should be evaluated.
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Postoperative bleeding remains one of the most frequent, but rarely life-threatening complications in thyroid surgery. Although arterial bleeding is the main cause of postoperative hemorrhage, most often no actively bleeding vessel can be found during revision. Therefore, the coagulation technique for larger vessels may play a minor role, and hemostatic agents could be of higher importance. In this descriptive, retrospective study, data of 279 patients with thyroid surgery (total of 414 thyroid lobectomies) were collected. We reviewed the electronic medical record by analyzing the histological, operative, laboratory and discharge reports in regards to postoperative bleeding. Of the 414 operated thyroid lobes, 2.4% (n = 10) bled. 1.4% (n = 6) needed reoperation while the other 1.0% (n = 4) could be treated conservatively. Hemostatic patches were applied 286 (69.1%) times. Of the 128 (30.9%) patch-free operated sides, 4.7% (n = 6) suffered postoperative bleeding. Tachosil® alone was used 211 (51.0%) times and bleeding occurred in 1.4% (n = 3). Without statistical significance (p = 0.08) the use of Tachosil® seems to help preventing postoperative bleeding. The combination with other patches doesn't appear to be more efficient.
Assuntos
Hemostáticos/uso terapêutico , Hemorragia Pós-Operatória/prevenção & controle , Glândula Tireoide/cirurgia , Combinação de Medicamentos , Feminino , Fibrinogênio/uso terapêutico , Hemostasia/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Reoperação/métodos , Estudos Retrospectivos , Trombina/uso terapêutico , Tireoidectomia/efeitos adversosRESUMO
We report the first case of a previously undocumented complication after posterior retroperitoneal adrenalectomy (PRA). Extensive diagnostic procedures for persisting abdominal pain led to diagnosis of an incisional hernia (IH) approximately 2.5 years after surgery for a pheochromocytoma of the right adrenal gland. Thus, IHs need to be recognized as a potential complication after PRA, particularly if the symptoms are non-specific. The differential diagnosis of an IH after PRA includes a type of spontaneous lumbar hernia due to a pre-existing weakness of the abdominal wall however the treatment for both type of hernias is similar by mesh repair. A possible risk factor for IH after PRA might be obesity, due to different factors including difficulties in closing the fascia in depth under subcutaneous tissue.
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With an incidence of less than 1%, paraduodenal hernias are very rare but account for ~0.2-5.8% of mechanical small bowel obstruction and carry a mortality rate of 20-50%. Right-sided paraduodenal hernias are three times less frequent than left-sided paraduodenal hernias. We report the case of a 37-year-old man who suffered from colicky abdominal pain accompanied by vomiting. The computed tomography scan showed a mechanical ileus, caused by a presumed paraduodenal hernia, and we chose an elective laparoscopic surgical approach. The patient recovered quickly and was discharged on the second postoperative day. Paraduodenal hernias are a diagnostic challenge as they are typically characterized by long-term non-specific abdominal symptoms and are only detected in the event of acute intestinal obstruction. Until now, laparoscopic therapy has only been described in eight case reports and we review this rare condition and the surgical options.
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Pentraxin 3 (PTX3) is an acute phase protein. Our goal was to assess PTX3 as a predictor of systemic inflammatory response syndrome (SIRS), death and disease severity in acute pancreatitis (AP) in comparison to C-reactive protein (CRP) and the APACHE II score. From April 2011 to January 2015, 142 patients with AP were included in this single center post hoc analysis of prospectively collected data at the University Hospital Basel, Switzerland. Disease severity was rated by the revised Atlanta criteria (rAC). Inflammatory response was measured by the SIRS criteria. PTX3, CRP and APACHE II score were measured. Patients median PTX3 plasma concentrations in AP were higher in moderate (3.311 ng/ml) and severe (3.091 ng/ml) than in mild disease (2.461 ng/ml). Overall, 59 occurrences of SIRS or death were observed. In the prediction of SIRS or death, PTX3 was inferior to CRP and APACHE II, with modest predictive discriminatory ability of all three markers and AUC of 0.54, 0.69 and 0.69, respectively. Upon combination of CRP with PTX3, AUC was 0.7. PTX3 seems to be inferior to CRP and APACHE II in the prediction of SIRS or death in AP and does not seem to improve the predictive value of CRP upon combination of both parameters.
Assuntos
Proteína C-Reativa/genética , Pancreatite/sangue , Componente Amiloide P Sérico/genética , Síndrome de Resposta Inflamatória Sistêmica/sangue , APACHE , Adulto , Idoso , Biomarcadores/sangue , Morte , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pancreatite/diagnóstico , Pancreatite/patologia , Índice de Gravidade de Doença , Síndrome de Resposta Inflamatória Sistêmica/diagnóstico , Síndrome de Resposta Inflamatória Sistêmica/patologiaRESUMO
OBJECTIVES: The aims of this study were to assess whether copeptin, pro-atrial natriuretic peptide, proadrenomedullin, and cortisol are associated with disease severity in patients with acute pancreatitis (AP) and to compare their ability in predicting organ failure or death. METHODS: From April 2011 to January 2015, 142 patients with AP were included in this prospective single-center study and observed for 4 days. Disease severity was rated by the Atlanta 1992 and 2012 criteria and organ failure by the modified Marshall score. The aforementioned laboratory markers, C-reactive protein, and procalcitonin were measured. RESULTS: Patients with moderate to severe AP showed significantly higher plasma concentrations of all biomarkers than did those with mild AP. Overall, 30 organ failures or deaths occurred. All biomarkers except cortisol had only modest discriminatory ability, with areas under the receiver operating characteristic curve (AUCs) between 0.44 and 0.66. Cortisol showed an AUC of 0.78 compared with the Acute Physiology and Chronic Health Evaluation II score with an AUC of 0.75. CONCLUSIONS: Cortisol was the best predictor of organ failure or death. All biomarkers were associated with disease severity to a similar degree as C-reactive protein, the criterion-standard marker in AP. Further studies are warranted to define their clinical role.
Assuntos
Biomarcadores/sangue , Hidrocortisona/sangue , Avaliação de Resultados em Cuidados de Saúde/métodos , Pancreatite/sangue , Doença Aguda , Adulto , Idoso , Idoso de 80 Anos ou mais , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/diagnóstico , Feminino , Humanos , Inflamação/sangue , Inflamação/diagnóstico , Masculino , Pessoa de Meia-Idade , Neurotransmissores/sangue , Pancreatite/diagnóstico , Prognóstico , Estudos Prospectivos , Curva ROCRESUMO
A healthy woman volunteered to participate as "healthy control" in a study. An increased level of procalcitonin (PCT) was detected and remained elevated on follow-up measurements. As calcitonin levels were elevated as well, thyroid ultrasound was performed which revealed nodes in both thyroid lobes, one of them showing metabolic activity in positron emission tomography-computed tomography scan. To exclude a malignant thyroid cancer despite the negative findings in a fine needle aspiration the patient underwent thyroidectomy and a medullary thyroid carcinoma (MTC) was detected in the right lobe. MTC is a rare endocrine tumor with a poor prognosis once having spread, therefore early detection remains a priority for the outcome. Screening parameter is serum calcitonin, in absence of infection the pro-hormone PCT can be used as a screening parameter as well with high sensitivity.
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BACKGROUND: OX40 is a TNF receptor family member expressed by activated T cells. Its triggering by OX40 ligand promotes lymphocyte survival and memory generation. Anti-OX40 agonistic monoclonal antibodies (mAb) are currently being tested in cancer immunotherapy. We explored the prognostic significance of tumor infiltration by OX40+ cells in a large colorectal cancer (CRC) collective. METHODS: OX40 gene expression was analyzed in 50 freshly excised CRC and corresponding healthy mucosa by qRT-PCR. A tissue microarray including 657 clinically annotated CRC specimens was stained with anti-OX40, -CD8 and -FOXP3 mAbs by standard immunohistochemistry. The CRC cohort was randomly split into training and validation sets. Correlations between CRC infiltration by OX40+ cells alone, or in combination with CD8+ or FOXP3+ cells, and clinical-pathological data and overall survival were comparatively evaluated. RESULTS: OX40 gene expression in CRC significantly correlated with FOXP3 and CD8 gene expression. High CRC infiltration by OX40+ cells was significantly associated with favorable prognosis in training and validation sets in univariate, but not multivariate, Cox regression analysis. CRC with OX40(high)/CD8(high) infiltration were characterized by significantly prolonged overall survival, as compared to tumors with OX40(low)/CD8(high), OX40(high)/CD8(low) or OX40(low)/CD8(low) infiltration in both uni- and multivariate analysis. In contrast, prognostic significance of OX40+ and FOXP3+ cell infiltration was not enhanced by a combined evaluation. Irrespective of TNM stage, CRC with OX40(high)/CD8(high) density infiltrates showed an overall survival similar to that of all stage I CRC included in the study. CONCLUSIONS: OX40(high)/CD8(high) density tumor infiltration represents an independent, favorable, prognostic marker in CRC with an overall survival similar to stage I cancers.
Assuntos
Biomarcadores Tumorais/metabolismo , Antígenos CD8/metabolismo , Linfócitos T CD8-Positivos/imunologia , Neoplasias Colorretais/metabolismo , Fatores de Transcrição Forkhead/metabolismo , Linfócitos do Interstício Tumoral/imunologia , Receptores OX40/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Antígenos CD8/genética , Linfócitos T CD8-Positivos/metabolismo , Neoplasias Colorretais/genética , Neoplasias Colorretais/imunologia , Neoplasias Colorretais/mortalidade , Feminino , Seguimentos , Fatores de Transcrição Forkhead/genética , Humanos , Técnicas Imunoenzimáticas , Linfócitos do Interstício Tumoral/metabolismo , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Prognóstico , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Receptores OX40/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Taxa de Sobrevida , Análise Serial de TecidosRESUMO
Colorectal cancer (CRC) infiltration by cells expressing myeloperoxidase (MPO) or CD8 positive T lymphocytes has been shown to be independently associated with favorable prognosis. We explored the relationship occurring between CD8+ and MPO+ cell CRC infiltration, its impact on clinical-pathological features and its prognostic significance in a tissue microarray (TMA) including 1,162 CRC. We observed that CRC showing high MPO+ cell infiltration are characterized by a prognosis as favorable as that of cancers with high CD8+ T cell infiltration. However, MPO+ and CD8+ CRC infiltrating cells did not synergize in determining a more favorable outcome, as compared with cancers showing MPOhigh/CD8low or MPOlow/CD8high infiltrates. Most importantly, we identified a subgroup of CRC with MPOlow/CD8low tumor infiltration characterized by a particularly severe prognosis. Intriguingly, although MPO+ and CD8+ cells did not co-localize in CRC infiltrates, an increased expression of TIA-1 and granzyme-B was detectable in T cells infiltrating CRC with high MPO+ cell density.
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Colorectal cancer is the third most common cancer in humans. Cancer has always been regarded as a disease of genetic defects such as gene mutations and deletions, chromosomal abnormalities, which lead to the loss of function of tumor-suppressor genes and/or gain of function or hyperactivation of oncogenes. Modifications on chromatin are considered to be the result of the opposing activities of histone acetyltransferases and histone deacetylases, which affect gene expression. Targeting histone deacetylases, histone deacetylase inhibitors are promising agents, as in solid tumors they are characterized by relatively low toxicity profile and antiproliferative activities. In colorectal cancer, the current experience is mainly experimental but promising. Histone deacetylase inhibitors are currently being admitted as monotherapy or combination therapy either with the conventional chemotherapy or with other agents. Valproic acid combined with ionization may enhance tumor response. Vorinostat was the first drug of this group used in clinical trial in combination with conventional chemotherapy and managed to stabilize advanced colorectal cancer. Experimental results show that combination therapy of vorinostat and decitabine (DNA methyl transferase inhibitor) may have optimal results. However, patients with colorectal cancer need to be recruited in randomized clinical trials in order to evaluate the potential efficiency of these agents.
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Antineoplásicos/uso terapêutico , Neoplasias Colorretais/terapia , Inibidores de Histona Desacetilases/uso terapêutico , Azacitidina/análogos & derivados , Azacitidina/uso terapêutico , Neoplasias Colorretais/radioterapia , Terapia Combinada , Decitabina , Humanos , Ácidos Hidroxâmicos/uso terapêutico , Ácido Valproico/uso terapêutico , VorinostatRESUMO
A 27-year-old patient in late pregnancy presented to the department of obstetrics with crampy abdominal pain located in the right flank, 3 years after a laparoscopic Roux-en-Y gastric bypass. Clinical investigation showed tenderness on palpation in the upper abdomen without signs of peritonitis. The cardiotocogram and blood tests were normal. The ultrasound showed a hydronephrosis on the right side, and a pigtail catheter was inserted. The abdominal symptoms did not abate and the abdominal surgeon was consulted 36 hours after admission. Diagnostic laparoscopy was performed promptly because of high suspicion of internal hernia (IH). Laparoscopy showed IH at the mesojejunal intermesenteric defect with a herniated common channel and volvulus of the anastomosis. Conversion to open reduction and complete closure with non-absorbable interrupted sutures was performed. Small bowel resection was avoided. The patient was discharged 10 days after the operation and a healthy boy was born 4 weeks later.
Assuntos
Derivação Gástrica/efeitos adversos , Hérnia Abdominal/etiologia , Enteropatias/etiologia , Obesidade Mórbida/cirurgia , Complicações Pós-Operatórias , Complicações na Gravidez , Adulto , Feminino , Derivação Gástrica/métodos , Hérnia Abdominal/diagnóstico , Hérnia Abdominal/cirurgia , Herniorrafia , Humanos , Hidronefrose/diagnóstico , Hidronefrose/etiologia , Hidronefrose/terapia , Recém-Nascido , Enteropatias/diagnóstico , Enteropatias/patologia , Enteropatias/cirurgia , Volvo Intestinal/diagnóstico , Volvo Intestinal/etiologia , Volvo Intestinal/cirurgia , Laparoscopia , Masculino , Obesidade Mórbida/complicações , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/cirurgia , Gravidez , Complicações na Gravidez/diagnóstico , Complicações na Gravidez/cirurgiaRESUMO
AIMS: A trend towards local excision of early rectal cancers has prompted us to investigate if immunoprofiling might help in predicting lymph node involvement in this subgroup. METHODS: A tissue microarray of 126 biopsies of early rectal cancer (T1 and T2) was stained for several immunomarkers of the innate and the adaptive immune response. Patients' survival and nodal status were analyzed and correlated with infiltration of the different immune cells. RESULTS: Of all tested markers, only CD8 (P = 0.005) and TIA-1 (P = 0.05) were significantly more frequently detectable in early rectal cancer biopsies of node negative as compared to node positive patients. Although these two immunomarkers did not display prognostic effect "per se," CD8+ and, marginally, TIA-1 T cell infiltration could predict nodal involvement in univariate logistic regression analysis (OR 0.994; 95% CI 0.992-0.996; P = 0.009 and OR 0.988; 95% CI 0.984-0.994; P = 0.05, resp.). An algorithm significantly predicting the nodal status in early rectal cancer based on CD8 together with vascular invasion and tumor border configuration could be calculated (P < 0.00001). CONCLUSION: Our data indicate that in early rectal cancers absence of CD8+ T-cell infiltration helps in predicting patients' nodal involvement.
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Linfócitos T CD8-Positivos/imunologia , Neoplasias do Colo/patologia , Neoplasias Retais/patologia , Imunidade Adaptativa , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Colo/imunologia , Feminino , Humanos , Metástase Linfática , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/metabolismo , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Neoplasias Retais/imunologiaRESUMO
BACKGROUND: Surgical site infections are the most common hospital-acquired infections among surgical patients. The administration of surgical antimicrobial prophylaxis reduces the risk of surgical site infections . The optimal timing of this procedure is still a matter of debate. While most studies suggest that it should be given as close to the incision time as possible, others conclude that this may be too late for optimal prevention of surgical site infections. A large observational study suggests that surgical antimicrobial prophylaxis should be administered 74 to 30 minutes before surgery. The aim of this article is to report the design and protocol of a randomized controlled trial investigating the optimal timing of surgical antimicrobial prophylaxis. METHODS/DESIGN: In this bi-center randomized controlled trial conducted at two tertiary referral centers in Switzerland, we plan to include 5,000 patients undergoing general, oncologic, vascular and orthopedic trauma procedures. Patients are randomized in a 1:1 ratio into two groups: one receiving surgical antimicrobial prophylaxis in the anesthesia room (75 to 30 minutes before incision) and the other receiving surgical antimicrobial prophylaxis in the operating room (less than 30 minutes before incision). We expect a significantly lower rate of surgical site infections with surgical antimicrobial prophylaxis administered more than 30 minutes before the scheduled incision. The primary outcome is the occurrence of surgical site infections during a 30-day follow-up period (one year with an implant in place). When assuming a 5% surgical site infection risk with administration of surgical antimicrobial prophylaxis in the operating room, the planned sample size has an 80% power to detect a relative risk reduction for surgical site infections of 33% when administering surgical antimicrobial prophylaxis in the anesthesia room (with a two-sided type I error of 5%). We expect the study to be completed within three years. DISCUSSION: The results of this randomized controlled trial will have an important impact on current international guidelines for infection control strategies in the hospital. Moreover, the results of this randomized controlled trial are of significant interest for patient safety and healthcare economics. TRIAL REGISTRATION: This trial is registered on ClinicalTrials.gov under the identifier NCT01790529.
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Antibacterianos/administração & dosagem , Antibioticoprofilaxia/métodos , Projetos de Pesquisa , Procedimentos Cirúrgicos Operatórios/efeitos adversos , Infecção da Ferida Cirúrgica/prevenção & controle , Protocolos Clínicos , Esquema de Medicação , Humanos , Fatores de Risco , Infecção da Ferida Cirúrgica/microbiologia , Suíça , Centros de Atenção Terciária , Fatores de Tempo , Resultado do TratamentoRESUMO
PURPOSE: Colorectal cancer infiltration by CD16(+) myeloid cells correlates with improved prognosis. We addressed mechanistic clues and gene and protein expression of cytokines potentially associated with macrophage polarization. EXPERIMENTAL DESIGN: GM-CSF or M-CSF-stimulated peripheral blood CD14(+) cells from healthy donors were cocultured with colorectal cancer cells. Tumor cell proliferation was assessed by (3)H-thymidine incorporation. Expression of cytokine genes in colorectal cancer and autologous healthy mucosa was tested by quantitative, real-time PCR. A tumor microarray (TMA) including >1,200 colorectal cancer specimens was stained with GM-CSF- and M-CSF-specific antibodies. Clinicopathological features and overall survival were analyzed. RESULTS: GM-CSF induced CD16 expression in 66% ± 8% of monocytes, as compared with 28% ± 1% in cells stimulated by M-CSF (P = 0.011). GM-CSF but not M-CSF-stimulated macrophages significantly (P < 0.02) inhibited colorectal cancer cell proliferation. GM-CSF gene was expressed to significantly (n = 45, P < 0.0001) higher extents in colorectal cancer than in healthy mucosa, whereas M-CSF gene expression was similar in healthy mucosa and colorectal cancer. Accordingly, IL1ß and IL23 genes, typically expressed by M1 macrophages, were expressed to significantly (P < 0.001) higher extents in colorectal cancer than in healthy mucosa. TMA staining revealed that GM-CSF production by tumor cells is associated with lower T stage (P = 0.02), "pushing" growth pattern (P = 0.004) and significantly (P = 0.0002) longer survival in mismatch-repair proficient colorectal cancer. Favorable prognostic effect of GM-CSF production by colorectal cancer cells was confirmed by multivariate analysis and was independent from CD16(+) and CD8(+) cell colorectal cancer infiltration. M-CSF expression had no significant prognostic relevance. CONCLUSIONS: GM-CSF production by tumor cells is an independent favorable prognostic factor in colorectal cancer.
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Biomarcadores Tumorais/metabolismo , Neoplasias Colorretais/mortalidade , Fator Estimulador de Colônias de Granulócitos e Macrófagos/metabolismo , Macrófagos/patologia , Monócitos/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Estudos de Casos e Controles , Proliferação de Células , Quimiocinas/genética , Quimiocinas/metabolismo , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Citocinas/genética , Citocinas/metabolismo , Feminino , Seguimentos , Perfilação da Expressão Gênica , Humanos , Imunocompetência , Técnicas Imunoenzimáticas , Fator Estimulador de Colônias de Macrófagos/metabolismo , Macrófagos/metabolismo , Masculino , Pessoa de Meia-Idade , Monócitos/metabolismo , Gradação de Tumores , Invasividade Neoplásica , Estadiamento de Neoplasias , Prognóstico , Reação em Cadeia da Polimerase em Tempo Real , Taxa de Sobrevida , Análise Serial de TecidosRESUMO
A 90-year-old woman presented with abdominal pain and vomiting. Initial investigations revealed diffuse abdominal tenderness and fever, combined with leucocytosis and marked elevation of C reactive protein levels. Abdominal CT demonstrated segmental bowel wall thickening in the jejunum near the tip of a ventriculoperitoneal (VP) shunt, which had been placed 17 years before because of hydrocephalus. Pneumobilia was present but no ectopic gallstone was detected at the initial analysis and there were no signs of mechanical ileus. Immediate laparoscopy was performed to exclude small bowel ischaemia. Owing to purulent ascites the VP shunt was externalised, supposing VP shunt infection with reactive jejunitis to be the main problem. Antibiotic treatment was then administered and the remaining part of the shunt was removed 6 days later. However, clinical signs of intestinal obstruction have been aggravated. Therefore, a laparoscopy was repeated 3 days later and a gallstone ileus was diagnosed. After enterolithotomy through a minilaparotomy, the patient was fully recovered.