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1.
Ann Oncol ; 34(1): 91-100, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36209981

RESUMEN

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).


Asunto(s)
Gemcitabina , Neoplasias Pancreáticas , Humanos , Desoxicitidina , Estudios Prospectivos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/cirugía , Neoplasias Pancreáticas/patología , Albúminas , Paclitaxel , Terapia Neoadyuvante , Adyuvantes Inmunológicos/uso terapéutico , Neoplasias Pancreáticas
2.
Int J Colorectal Dis ; 36(10): 2247-2259, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-34455473

RESUMEN

BACKGROUND: Anastomotic leakage represents a major complication following resections in colorectal surgery. Among others, intestinal inflammation such as in inflammatory bowel disease is a significant risk factor for disturbed anastomotic healing. Despite technical advancements and several decades of focused research, the underlying mechanisms remain incompletely understood. Animal experiments will remain the backbone of this research in the near future. Here, instructions on a standardized and reproducible murine model of preoperative colitis and colorectal anastomosis formation are provided to amplify research on anastomotic healing during inflammatory disease. METHODS: We demonstrate the combination of experimental colitis and colorectal anastomosis formation in a mouse model. The model allows for monitoring of anastomotic healing during inflammatory disease through functional outcomes, clinical scores, and endoscopy and histopathological examination, as well as molecular analysis. DISCUSSION: Postoperative weight loss is used as a parameter to monitor general recovery. Functional stability can be measured by recording bursting pressure and location. Anastomotic healing can be evaluated macroscopically from the luminal side by endoscopic scoring and from the extraluminal side by assessing adhesion and abscess formation or presence of dehiscence. Histologic examination allows for detailed evaluation of the healing process. CONCLUSION: The murine model presented in this paper combines adjustable levels of experimental colitis with a standardized method for colorectal anastomosis formation. Extensive options for sample analysis and evaluation of clinical outcomes allow for detailed research of the mechanisms behind defective anastomotic healing.


Asunto(s)
Fuga Anastomótica , Colitis , Anastomosis Quirúrgica/efectos adversos , Fuga Anastomótica/etiología , Animales , Colon/cirugía , Ratones , Ratas , Ratas Wistar , Cicatrización de Heridas
3.
Br J Surg ; 105(7): 784-796, 2018 06.
Artículo en Inglés | MEDLINE | ID: mdl-29088493

RESUMEN

BACKGROUND: It is not clear whether resection of the primary tumour (when there are metastases) alters survival and/or whether resection is associated with increased morbidity. This systematic review and meta-analysis assessed the prognostic value of primary tumour resection in patients presenting with metastatic colorectal cancer. METHODS: A systematic review of MEDLINE/PubMed was performed on 12 March 2016, with no language or date restrictions, for studies comparing primary tumour resection versus conservative treatment without primary tumour resection for metastatic colorectal cancer. The quality of the studies was assessed using the MINORS and STROBE criteria. Differences in survival, morbidity and mortality between groups were estimated using random-effects meta-analysis. RESULTS: Of 37 412 initially screened articles, 56 retrospective studies with 148 151 patients met the inclusion criteria. Primary tumour resection led to an improvement in overall survival of 7·76 (95 per cent c.i. 5·96 to 9·56) months (risk ratio (RR) for overall survival 0·50, 95 per cent c.i. 0·47 to 0·53), but did not significantly reduce the risk of obstruction (RR 0·50, 95 per cent c.i. 0·16 to 1·53) or bleeding (RR 1·19, 0·48 to 2·97). Neither was the morbidity risk altered (RR 1·14, 0·77 to 1·68). Heterogeneity between the studies was high, with a calculated I2 of more than 50 per cent for most outcomes. CONCLUSION: Primary tumour resection may provide a modest survival advantage in patients presenting with metastatic colorectal cancer.


Asunto(s)
Neoplasias Colorrectales/secundario , Neoplasias Colorrectales/cirugía , Neoplasias Colorrectales/complicaciones , Neoplasias Colorrectales/mortalidad , Terapia Combinada , Hemorragia Gastrointestinal/etiología , Hemorragia Gastrointestinal/prevención & control , Humanos , Obstrucción Intestinal/etiología , Obstrucción Intestinal/prevención & control , Complicaciones Posoperatorias/mortalidad , Análisis de Supervivencia
4.
Br J Surg ; 104(2): e182-e188, 2017 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-28121036

RESUMEN

BACKGROUND: Patients with obstructive jaundice due to periampullary tumours may undergo preoperative biliary drainage (PBD). The effect of PBD on the microbiome of the biliary system and on postoperative outcome remains unclear. METHODS: A single-centre retrospective study of patients with obstructive jaundice due to periampullary cancer, treated between July 2007 and July 2015, was undertaken. Intraoperative bile samples were obtained for microbiological analysis after transection of the common bile duct. Postoperative complications were registered. RESULTS: Of 290 patients treated, intraoperative bile samples were present for 172 patients (59·3 per cent) who had PBD and 118 (40·7 per cent) who did not. Contamination of bile was increased significantly in patients who underwent stenting (97·1 per cent versus 18·6 per cent in those without stenting; P < 0·001). PBD resulted in a shift in the biliary microbiome from Escherichia coli in non-stented patients (45 per cent versus 19·2 per cent in stented patients; P = 0·009) towards increased contamination with Enterococcus faecalis (9 versus 37·7 per cent respectively; P = 0·008) and Enterobacter cloacae (0 versus 20·4 per cent; P = 0·033). This shift was associated with a high incidence of bacterial resistance against ampicillin-sulbactam (63·6 per cent versus 18 per cent in patients with no PBD; P < 0·001), piperacillin-tazobactam (30·1 versus 0 per cent respectively; P = 0·003), ciprofloxacin (28·5 versus 5 per cent; P = 0·047) and imipenem (26·6 versus 0 per cent; P = 0·011). The rate of wound infection was higher in patients with a positive bile culture (21·0 per cent versus 6 per cent in patients with sterile bile; P = 0·002). Regression analysis revealed the presence of Enterococcus faecium (odds ratio 2·83, 95 per cent c.i. 1·17 to 6·84; P = 0·021) and Citrobacter species (odds ratio 5·09, 1·65 to 15·71; P = 0·005) as independent risk factors for postoperative wound infection. CONCLUSION: There are fundamental differences in the biliary microbiome of patients with periampullary cancer who undergo PBD and those who do not. PBD induces a shift of the biliary microbiome towards a more aggressive and resistant spectrum, which requires a differentiated perioperative antibiotic treatment strategy.


Asunto(s)
Bilis/microbiología , Neoplasias del Conducto Colédoco/complicaciones , Drenaje , Ictericia Obstructiva/terapia , Microbiota , Cuidados Preoperatorios , Anciano , Ampolla Hepatopancreática/cirugía , Antibacterianos/uso terapéutico , Colangitis/epidemiología , Citrobacter/aislamiento & purificación , Neoplasias del Conducto Colédoco/cirugía , Farmacorresistencia Bacteriana Múltiple , Infecciones por Enterobacteriaceae/epidemiología , Enterococcus faecalis/aislamiento & purificación , Femenino , Alemania/epidemiología , Infecciones por Bacterias Grampositivas/epidemiología , Humanos , Ictericia Obstructiva/etiología , Masculino , Análisis de Regresión , Estudios Retrospectivos , Factores de Riesgo , Stents , Infección de la Herida Quirúrgica/epidemiología
5.
BMC Cancer ; 17(1): 130, 2017 02 14.
Artículo en Inglés | MEDLINE | ID: mdl-28193264

RESUMEN

BACKGROUND: Despite our growing knowledge about the pathomechanisms of cancer cachexia, a whole clinical picture of the cachectic patient is still missing. Our objective was to evaluate the clinical characteristics in cancer patients with and without cachexia to get the whole picture of a cachectic patient. METHODS: Cancer patients of the University Clinic "Klinikum rechts der Isar" with gastrointestinal, gynecological, hematopoietic, lung and some other tumors were offered the possibility to take part in the treatment concept including a nutrition intervention and an individual training program according to their capability. We now report on the first 503 patients at the time of inclusion in the program between March 2011 and October 2015. We described clinical characteristics such as physical activity, quality of life, clinical dates and food intake. RESULTS: Of 503 patients with cancer, 131 patients (26.0%) were identified as cachectic, 369 (73.4%) as non-cachectic. The change in cachexia were 23% reduced capacity performance (108 Watt for non-cachectic-patients and 83 Watt for cachectic patients) and 12% reduced relative performance (1.53 Watt/kg for non-cachectic and 1.34 Watt/kg for cachectic patients) in ergometry test. 75.6% of non-cachectic and 54.3% of cachectic patients still received curative treatment. CONCLUSION: Cancer cachectic patients have multiple symptoms such as anemia, impaired kidney function and impaired liver function with elements of mild cholestasis, lower performance and a poorer quality of life in the EORTC questionnaire. Our study reveals biochemical and clinical specific features of cancer cachectic patients.


Asunto(s)
Caquexia/terapia , Neoplasias/complicaciones , Modalidades de Fisioterapia , Calidad de Vida/psicología , Anemia/etiología , Caquexia/epidemiología , Caquexia/etiología , Caquexia/psicología , Ingestión de Alimentos , Ejercicio Físico , Femenino , Humanos , Riñón/fisiopatología , Hígado/fisiopatología , Pruebas de Función Hepática , Masculino , Neoplasias/fisiopatología , Estado Nutricional
6.
Zentralbl Chir ; 141(3): 302-9, 2016 Jun.
Artículo en Alemán | MEDLINE | ID: mdl-24647814

RESUMEN

BACKGROUND: It seems that the experience gained in the courses of surgical training in medical education does not really motivate students for surgery in Germany. Inspired by this problem the Department of Surgery of the Klinikum rechts der Isar, Technical University of Munich has developed a substantial reform for the internship since 2009 with the aim of not only improving the quality of education significantly, but also the attractiveness and thus the fascination for the subject. METHODS: Based on the slogan "We want to awaken your fascination for surgery" a structured and standardised training of all students in their internship regardless of the ward or section and local conditions was developed. For this purpose a completely new curriculum was steadily implemented into clinical practice, based on the following four basic principles: (i) integration and perception in the clinic, (ii) central and peripheral maintenance, (iii) systematic and individual training, (iv) evaluation and feedback at all levels. To analyse the effectiveness of the reform, standardised evaluations by students and faculty were carried out regularly. RESULTS: To date, since the beginning of the reform in 2009, there has been an approximately linear increase in the number of students in the PJ surgery. The daily systematic courses showed a good to excellent rating in all formats. The comparison showed a clear increasing trend in all the values, in particular, the "integration into the overall hospital" significantly improved (mean, 4.7 vs. 5.5, p = 0.003). However, the point "motivating for surgery" (mean, 3.3) remains at a low level. But also medical educators were satisfied with the new curriculum for the internship students (mean, 4.5). CONCLUSION: The reform was adopted universally in a very positive manner and the current data support the need for such a reform. Overall, the reform showed a positive development of the internship training in the surgical department of the faculty. The satisfaction of the students and teachers could be increased by gradual implementation of the reform. Even if a lot of individual aspects gain a higher acceptance, the main concern, the inspiration of the "fascination" of the central surgical field, the training in the operating room, seems to succeed only partially.


Asunto(s)
Competencia Clínica , Curriculum , Cirugía General/educación , Internado y Residencia , Preceptoría , Actitud del Personal de Salud , Selección de Profesión , Alemania , Humanos
7.
Z Gastroenterol ; 53(12): 1447-95, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-26666283

RESUMEN

Chronic pancreatitis is a disease of the pancreas in which recurrent inflammatory episodes result in replacement of pancreatic parenchyma by fibrous connective tissue. This fibrotic reorganization of the pancreas leads to a progressive exocrine and endocrine pancreatic insufficiency. In addition, characteristic complications arise, such as pseudocysts, pancreatic duct obstructions, duodenal obstruction, vascular complications, obstruction of the bile ducts, malnutrition and pain syndrome. Pain presents as the main symptom of patients with chronic pancreatitis. Chronic pancreatitis is a risk factor for pancreatic carcinoma. Chronic pancreatitis significantly reduces the quality of life and the life expectancy of affected patients. These guidelines were researched and compiled by 74 representatives from 11 learned societies and their intention is to serve evidence-based professional training as well as continuing education. On this basis they shall improve the medical care of affected patients in both the inpatient and outpatient sector. Chronic pancreatitis requires an adequate diagnostic workup and systematic management, given its severity, frequency, chronicity, and negative impact on the quality of life and life expectancy.


Asunto(s)
Endoscopía Gastrointestinal/normas , Pancreatectomía/normas , Pruebas de Función Pancreática/normas , Pancreatitis/diagnóstico , Pancreatitis/terapia , Guías de Práctica Clínica como Asunto , Enfermedad Crónica , Alemania , Humanos , Estados Unidos
8.
Langenbecks Arch Surg ; 399(6): 783-8, 2014 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-24852218

RESUMEN

PURPOSE: The aim of this study is to define the significance of hyponatremia as a marker of anastomotic leakage after colorectal surgery. METHODS: All anastomoses in colorectal surgery performed at a single institution between July 2007 and July 2012 (n = 1,106) were retrospectively identified. Serum sodium levels and leukocyte values measured when an anastomotic leak was diagnosed by CT scan and/or surgical reintervention (n = 81) were compared to the values preferably on postoperative day 5 in the absence of an anastomotic leak (n = 1,025). RESULTS: The leak rate in anastomoses of the rectum was 9.0 %, while the leak rate of the other anastomoses was 5.4 %. Mean serum sodium level was 138.8 mmol/l in the group with an anastomotic leak and 140.5 mmol/l in the group without. Hyponatremia (<136 mmol/l) was present in 23 % of patients in the group with an anastomotic leak and in 15 % in the group without (p < 0.001). In multivariate analysis, leukocytes and serum sodium level remained as significant markers of an anastomotic leak. As a marker of an anastomotic leak, hyponatremia had a specificity of 93 % and a sensitivity of 23 %, while the presence of either leukocytosis or hyponatremia had a sensitivity of 68 %, a specificity of 75 %, a positive predictive value of 18 %, and a negative predictive value of 97 %. CONCLUSIONS: Hyponatremia could be a specific and relevant marker of anastomotic leakage after colorectal surgery. If hyponatremia and leukocytosis are present after colorectal surgery, anastomotic leakage should be suspected and a CT scan with rectal contrast dye is recommended.


Asunto(s)
Fuga Anastomótica/sangre , Fuga Anastomótica/diagnóstico , Neoplasias Colorrectales/cirugía , Hiponatremia/etiología , Leucocitosis/etiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Fuga Anastomótica/etiología , Biomarcadores/sangre , Neoplasias Colorrectales/sangre , Neoplasias Colorrectales/patología , Femenino , Humanos , Hiponatremia/diagnóstico , Recuento de Leucocitos , Leucocitosis/diagnóstico , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Sensibilidad y Especificidad , Adulto Joven
9.
Eur J Cancer Care (Engl) ; 23(5): 585-93, 2014 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-24393204

RESUMEN

Little is known about the quality of post-operative communications following oncological surgery and the satisfaction of patients with the communication process. Thirty-eight patients who underwent surgery for primary gastrointestinal cancer were interviewed before being discharged from the hospital. The patients' recall of information concerning the surgery, histological diagnosis, post-operative therapy and treatment goal was assessed. The congruence between the information provided by the surgeons and that retained by the patients was evaluated. The information provided by the surgeons about the diagnosis, histology and post-operative therapy plan was correctly recalled by over 92%, 81% and 97% of the patients respectively. Only 70% of the patients correctly recalled information about the goal of the treatment. Moreover, patients receiving only palliative treatment showed less recall of information about the treatment goal than patients receiving curative treatment (33% versus 89%). The surgeons reported that only 35% of the patients left the hospital completely informed. Overall, the patients were highly satisfied with their communication with their surgeon, and the patients' recall of information was generally good. The information given by the surgeons was often incomplete, however. Our explorative analysis showed that the quality of communication was often worse for patients with a palliative treatment goal than for patients with a curative treatment goal.


Asunto(s)
Neoplasias Gastrointestinales/cirugía , Satisfacción del Paciente , Relaciones Médico-Paciente , Cirujanos/psicología , Adulto , Anciano , Anciano de 80 o más Años , Comunicación , Femenino , Humanos , Masculino , Recuerdo Mental , Persona de Mediana Edad , Cuidados Paliativos , Alta del Paciente , Cuidados Posoperatorios , Periodo Posoperatorio , Encuestas y Cuestionarios
10.
Br J Cancer ; 108(9): 1846-53, 2013 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-23579209

RESUMEN

BACKGROUND: The aims of our study were to identify serum biomarkers that distinguish pancreatic cancer (pancreatic ductal adenocarcinoma, PDAC) patients from benign pancreatic disease patients and healthy subjects, and to assess the effects of jaundice on biomarker performance. METHODS: Isobaric tags for relative and absolute quantification were used to compare pooled serum and pancreatic juice samples from a test set of 59 and 25 subjects, respectively. Validation was undertaken in 113 independent subjects. RESULTS: Candidate proteins Complement C5, inter-α-trypsin inhibitor heavy chain H3, α1-ß glycoprotein and polymeric immunoglobulin receptor were elevated in cancer, as were the reference markers CA19-9 and Reg3A. Biliary obstruction had a significant effect on the performance of the markers, in particular within the PDAC group where the presence of jaundice was associated with a significant increase in the levels of all six proteins (P<0.01). Consequently, in the absence of jaundice, proteins showed reduced sensitivity for PDAC patients over benign subjects and healthy controls (HCs). Similarly, in the presence of jaundice, markers showed reduced specificity for PDAC patients over benign subjects with jaundice. Combining markers enabled improved sensitivity for non-jaundiced PDAC patients over HCs and improved specificity for jaundiced PDAC patients over jaundiced benign disease subjects. CONCLUSIONS: The presence-absence of jaundice in the clinical scenario severely impacts the performance of biomarkers for PDAC diagnosis and has implications for their clinical translation.


Asunto(s)
Biomarcadores de Tumor/sangre , Ictericia Obstructiva/sangre , Jugo Pancreático/citología , Neoplasias Pancreáticas/diagnóstico , Anciano , alfa-Globulinas/análisis , Antígenos de Neoplasias/sangre , Antígeno CA-19-9/sangre , Complemento C5/análisis , Femenino , Glicoproteínas/sangre , Humanos , Inmunoglobulinas/sangre , Ictericia Obstructiva/complicaciones , Lectinas Tipo C/sangre , Masculino , Persona de Mediana Edad , Neoplasias Pancreáticas/sangre , Proteínas Asociadas a Pancreatitis , Receptores de Inmunoglobulina Polimérica/análisis
11.
Zentralbl Chir ; 138(2): 144-50, 2013 Apr.
Artículo en Alemán | MEDLINE | ID: mdl-22392262

RESUMEN

BACKGROUND: According to the approval system for medical doctors, practical courses such as block practical training must be graded. The grading of the surgical block practical training at the Klinikum rechts der Isar, Technische Universität of Munich (TUM), was changed from single grades of each day to a final objective structured clinical examination (OSCE). We report about the experiences in the past 12 months with this relatively new form of examination. METHODS: An OSCE was established as a practical exam with seven stations about suture techniques, internal fixation, first-aid education, hygiene and sterility, clinical examination and perioperative management. The feasibility of a comprehensive OSCE with the necessary modifications was studied and the grades had been compared. RESULTS: In the past 12 months four surgical block placements for over three weeks had been organised with a total of 326 students. 309 students were admitted for the OSCE at the end of block practical training. The average score was 1.75. The medical student raters graded either equally or more stringently compared to the medical doctors. The transcript revealed in all OSCEs a normal distribution of grading with high validity. However, an adaptation of the evaluation forms and an extension of the stations with modified content was required to obtain the same test conditions for all students. The implementation of the OSCE on this scale is possible with adequate preparation time and sufficient financial support. The evaluation of the specimens after completion of the test were all positive. CONCLUSION: The new medical approval system calls for restructuring, not only in teaching but also in the form of examination of the courses. Through this practical test, those skills of a student will be assessed that cannot be tested by the IMPP exam. Moreover, this examination form provides an excellent preparation for the practical part of the oral state examination. This OSCE is even feasible with high numbers of students and offers with appropriate adaptation of the evaluation forms and test stations, a normal distribution of grading.


Asunto(s)
Educación de Postgrado en Medicina/normas , Evaluación Educacional/normas , Cirugía General/educación , Internado y Residencia/normas , Consejos de Especialidades/normas , Competencia Clínica/normas , Curriculum/normas , Estudios de Factibilidad , Alemania , Hospitales Universitarios , Humanos
12.
Cancer Epidemiol ; 86: 102440, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37572415

RESUMEN

BACKGROUND: Rectal cancer treatment has improved considerably due to the introduction of total meso-rectal excision, radio-chemotherapy, and high-resolution imaging. The aim of this observational cohort study was to quantify the effectiveness of these advances using high-quality data from a representative cohort of patients. METHODS: 20 281 non-metastasized cases retrieved from the Munich Cancer Registry database were divided into three time periods corresponding to before (1988-1997), partial (1998-2007), and full implementation (2008-2019) of clinical advances. Early-onset (<50 yrs.), middle-aged, elderly patient subgroups (> 70 yrs.) were compared. The overall effectiveness of evidence-based guideline adherence was also examined. RESULTS: Median survival improved by 1.5 yrs. from the first to the last time period. Relative survival increased from 74.9% (5-yr 95%CI[73.3 - 76.6]) to 79.2% (95%CI[77.8 - 80.5]). The incidence of locoregional recurrences was reduced dramatically by more than half (5-yr 17.7% (95%CI[16.5 - 18.8]); 6.7% (95%CI[6.1 - 7.3])). Gains in 5-yr relative survival were limited to early-onset and middle-aged patients with no significant improvement seen in elderly patients (Female 68.6% [63.9 - 73.3] to 67.6% [64.0 - 71.2]; Male 71.7% [65.9 - 77.4] to 74.0% [70.8 - 77.2]). CONCLUSIONS: Real-world evidence suggests that recent treatment advances have lead to an increase in prognosis for rectal cancer patients. However, more effort should be made to improve the implementation of new developments in elderly patients. Especially considering, that these cases represent a growing majority of diagnosed patients.


Asunto(s)
Neoplasias del Recto , Anciano , Persona de Mediana Edad , Humanos , Masculino , Femenino , Estadificación de Neoplasias , Pronóstico , Neoplasias del Recto/terapia , Neoplasias del Recto/patología , Estudios de Cohortes , Incidencia , Resultado del Tratamiento
13.
Br J Cancer ; 106(1): 133-40, 2012 Jan 03.
Artículo en Inglés | MEDLINE | ID: mdl-22108518

RESUMEN

BACKGROUND: There are no established biomarkers to identify tumour recurrence in stage II colon cancer. As shown previously, the enzymatic activity of the cyclin-dependent kinases 1 and 2 (CDK1 and CDK2) predicts outcome in breast cancer. Therefore, we investigated whether CDK activity identifies tumour recurrence in colon cancer. METHODS: In all, 254 patients with completely resected (R0) UICC stage II colon cancer were analysed retrospectively from two independent cohorts from Munich (Germany) and Leiden (Netherlands). None of the patients received adjuvant treatment. Development of distant metastasis was observed in 27 patients (median follow-up: 86 months). Protein expression and activity of CDKs were measured on fresh-frozen tumour samples. RESULTS: Specific activity (SA) of CDK1 (CDK1SA), but not CDK2, significantly predicted distant metastasis (concordance index=0.69, 95% confidence interval (CI): 0.55-0.79, P=0.036). Cutoff derivation by maximum log-rank statistics yielded a threshold of CDK1SA at 11 (SA units, P=0.029). Accordingly, 59% of patients were classified as high-risk (CDK1SA ≥11). Cox proportional hazard analysis revealed CDK1SA as independent prognostic variable (hazard ratio=6.2, 95% CI: 1.44-26.9, P=0.012). Moreover, CKD1SA was significantly elevated in microsatellite-stable tumours. CONCLUSION: Specific activity of CDK1 is a promising biomarker for metastasis risk in stage II colon cancer.


Asunto(s)
Neoplasias del Colon/enzimología , Quinasas Ciclina-Dependientes/metabolismo , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Secuencia de Bases , Neoplasias del Colon/patología , Cartilla de ADN , Femenino , Técnica del Anticuerpo Fluorescente , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Estudios Retrospectivos , Adulto Joven
14.
Eur J Nucl Med Mol Imaging ; 39(5): 846-51, 2012 May.
Artículo en Inglés | MEDLINE | ID: mdl-22278320

RESUMEN

PURPOSE: Despite recent advances in clinical imaging modalities, differentiation of pancreatic masses remains difficult. Here, we tested the diagnostic accuracy of molecular-based imaging including 3'-deoxy-3'-[(18)F]fluorothymidine (FLT) positron emission tomography (PET) and [(18)F]fluorodeoxyglucose (FDG) PET/CT in patients with suspected pancreatic masses scheduled to undergo surgery. METHODS: A total of 46 patients with pancreatic tumours suspicious for malignancy and scheduled for resective surgery were recruited prospectively. In 41 patients, FLT PET and FDG PET/CT scans were performed. A diagnostic CT performed on a routine basis was available in 31 patients. FLT PET and FDG PET/CT emission images were acquired according to standard protocols. Tracer uptake in the tumour [FDG and FLT standardized uptake value (SUV)] was quantified by the region of interest (ROI) technique. For FDG PET/CT analysis, correct ROI placement was ensured via side-by-side reading of corresponding CT images. RESULTS: Of 41 patients, 33 had malignancy, whereas 8 patients had benign disease. Visual analysis of FDG and FLT PET resulted in sensitivity values of 91% (30/33) and 70% (23/33), respectively. Corresponding specificities were 50% (4/8) for FDG PET and 75% (6/8) for FLT PET. In the subgroup of patients with contrast-enhanced CT (n = 31), sensitivities were 96% (PET/CT), 88% (CT alone), 92% (FDG PET) and 72% (FLT PET), respectively. Mean FLT uptake in all malignant tumours was 3.0 (range SUV(max) 1.1-6.5; mean FDG SUV(max) 7.9, range 3.3-17.8; p < 0.001). CONCLUSION: For differentiation of pancreatic tumours, FDG PET and FDG PET/CT showed a higher sensitivity but lower specificity than FLT PET. Interestingly, visual analysis of FLT PET led to two false-positive findings by misinterpreting physiological bowel uptake as pathological FLT uptake in the pancreas. Due to the limited number of patients, the clinical value of adding FLT PET to the diagnostic workup of pancreatic tumours remains to be determined.


Asunto(s)
Didesoxinucleósidos , Fluorodesoxiglucosa F18 , Imagen Multimodal/métodos , Neoplasias Pancreáticas/diagnóstico por imagen , Tomografía de Emisión de Positrones , Tomografía Computarizada por Rayos X , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Medios de Contraste , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/cirugía , Sensibilidad y Especificidad
15.
Eur Surg Res ; 48(3): 131-8, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-22572771

RESUMEN

BACKGROUND/AIMS: We aimed to analyze substance P (SP) and neprilysin (NEP), the membrane metallopeptidase that degrades SP, in chronic pancreatitis (CP). METHODS: SP and NEP mRNA levels were analyzed by qRT-PCR in tissue samples from 30 patients with CP and 8 organ donors. In addition, SP serum levels were determined before and after surgery in the same patients, by means of a competitive ELISA assay. Genetic and epigenetic analyses of the NEP gene were also performed. RESULTS: SP mRNA expression levels were higher in CP tissues compared to controls (p = 0.0152), while NEP mRNA showed no significant differences between CP and healthy subjects (p = 0.2102). In CP patients, SP serum levels correlated with those in tissue, and after surgical resection SP serum levels were reduced compared to the preoperative values. Failure of NEP to overexpress in CP tissues was associated with significant miR-128a overexpression (p = 0.02), rather than with mutations in the NEP coding region or the presence of hypermethylation sites in the NEP promoter region. CONCLUSION: Tissue and serum levels of SP were increased in CP, while NEP levels remained unaltered. In an SP/NEP-mediated pathway, it would appear that NEP fails to provide adequate surveillance of SP levels. Failure of NEP to overexpress could be associated with miRNA regulation.


Asunto(s)
Neprilisina/fisiología , Pancreatitis Crónica/etiología , Sustancia P/fisiología , Adulto , Anciano , Metilación de ADN , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neprilisina/sangre , Neprilisina/genética , Pancreatitis Crónica/sangre , Regiones Promotoras Genéticas , ARN Mensajero/análisis , Sustancia P/sangre , Sustancia P/genética
16.
Chirurgie (Heidelb) ; 93(6): 566-576, 2022 Jun.
Artículo en Alemán | MEDLINE | ID: mdl-35226123

RESUMEN

Surgical interventions should ideally treat an existing disease curatively and achieve this with a low complication rate and minimal trauma. In this sense, laparoscopic cholecystectomy has become established as the recognized standard for the treatment of cholecystolithiasis. Newer procedures, such as single-port surgery or natural orifice transluminal endoscopic surgery (NOTES) have recently emerged to reduce the already low interventional trauma even further and to provide a better cosmetic outcome. With all new methods the main aim is the reduction of the transabdominal access points. Based on published results and diagnosis-related groups (DRG) data, this article examines whether this goal has been achieved, also with respect to the overall quality of treatment and the complication rates. In this context and in addition to the already mentioned approaches, robotic cholecystectomy and the reduced port approach are also considered.


Asunto(s)
Colecistectomía Laparoscópica , Cirugía Endoscópica por Orificios Naturales , Robótica , Colecistectomía/métodos , Colecistectomía Laparoscópica/efectos adversos , Cirugía Endoscópica por Orificios Naturales/métodos
17.
Chirurgie (Heidelb) ; 93(10): 986-992, 2022 Oct.
Artículo en Alemán | MEDLINE | ID: mdl-35925138

RESUMEN

BACKGROUND: Patients with complicated appendicitis frequently develop postoperative septic complications. There are no uniform standards for the choice of perioperative antibiotic prophylaxis and the duration of postoperative antibiotic treatment. The purpose of this study was to investigate associations between microbiological samples and postoperative complications. METHODS: Patients with appendectomy and positive intraoperative swabs during 2013-2018 were included in this case-control study. Pathogen classes and their resistance patterns were evaluated in initial and follow-up swabs and compared in each of the groups with and without complications. RESULTS: A total of 870 patients underwent surgery during the period studied. Pathogen detection succeeded in 102 of 210 cases (48.6%) with suspected bacterial peritoneal contamination. Conversion from laparoscopic to open intra-abdominal perforation and the presence of an abscess were independent risk factors for wound infections in the multivariate analysis. The combination of different classes of pathogens resulted in significantly increased overall resistance to ampicillin/sulbactam in both the initial swabs (57%) and the follow-up swabs (73%). Resistant E. coli strains combined with certain anaerobes were also regularly detected in postoperative intra-abdominal abscesses. Piperacillin/tazobactam was effective against 83% of positive swabs in our resistance tests. CONCLUSION: Surgical treatment for complicated appendicitis remains the central therapeutic column. A regular review of the existing resistance patterns in perforated appendicitis can help to adjust and improve antibiotic treatment. Piperacillin/tazobactam should be used cautiously as a reserve antibiotic. A valid alternative is second or third generation cephalosporins in combination with metronidazole.


Asunto(s)
Apendicitis , Ampicilina/uso terapéutico , Antibacterianos/uso terapéutico , Apendicitis/complicaciones , Estudios de Casos y Controles , Cefalosporinas/uso terapéutico , Escherichia coli , Humanos , Metronidazol/uso terapéutico , Combinación Piperacilina y Tazobactam/uso terapéutico , Complicaciones Posoperatorias , Sulbactam/uso terapéutico
18.
Br J Cancer ; 105(2): 288-95, 2011 Jul 12.
Artículo en Inglés | MEDLINE | ID: mdl-21712827

RESUMEN

BACKGROUND: The transcription factor HOXC8 regulates many genes involved in tumour progression. This study was to investigate the role of HOXC8 in pancreatic ductal adenocarcinoma (PDAC) growth and metastasis. METHODS: The Hoxc8 expression was determined in 15 PDAC cell lines and human specimens by RT-polymerase chain reaction and/or immunohistochemistry. The effects of HOXC8 silencing by RNA interference were investigated by functional tests. RESULTS: The Hoxc8 mRNA expression in PDAC cell lines was negatively related to their growth in vivo. Except for Suit2-007 cells, only those with low Hoxc8 mRNA expression grew in nude rats. Successful down-regulation of HOXC8 expression caused increased proliferation, migration (P ≤ 0.05) and colony formation (P ≤ 0.05) in Suit2-007, Panc-1 and MIA PaCa-2 PDAC cells, respectively. The Hoxc8 mRNA levels in diseased human pancreas tissues were significantly increased over normal in PDAC and autoimmune chronic pancreatitis specimens (P<0.01, respectively), but negatively related to tumour stage (P=0.09). In primary and metastatic tumour samples, immunohistochemical staining for HOXC8 was stronger in surrounding than in neoplastic tissues. Furthermore, grading of primary carcinomas was negatively associated with HOXC8 staining (P=0.03). Liver metastases showed the lowest HOXC8 expression of all neoplastic lesions. CONCLUSION: These data indicate that HOXC8 expression is inversely related to PDAC progression and metastasis.


Asunto(s)
Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/patología , Proteínas de Homeodominio/genética , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patología , Adenocarcinoma/genética , Adenocarcinoma/patología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Animales , Estudios de Casos y Controles , Línea Celular Tumoral , Progresión de la Enfermedad , Femenino , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/fisiología , Proteínas de Homeodominio/antagonistas & inhibidores , Proteínas de Homeodominio/fisiología , Humanos , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , ARN Interferente Pequeño/farmacología , Ratas , Ratas Desnudas , Ensayos Antitumor por Modelo de Xenoinjerto , Adulto Joven
19.
Br J Surg ; 98(6): 768-83, 2011 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-21462364

RESUMEN

BACKGROUND: The standard treatment for resectable oesophageal squamous cell carcinoma (OSCC) is surgical resection with adequate lymphadenectomy. Most Western patients receive neoadjuvant chemotherapy or chemoradiotherapy (CRT). In recent years some patients have received CRT alone (definitive CRT, dCRT). This meta-analysis sought to clarify the benefits of neoadjuvant and definitive treatment for OSCC. METHODS: Eligible randomized controlled trials (RCTs) were identified using the Cochrane database, MEDLINE and Embase. Only RCTs with intention-to-treat analysis, and published hazard ratios (HRs) or estimates from survival data, were included. RESULTS: Nine RCTs involving neoadjuvant CRT versus surgery, eight involving neoadjuvant chemotherapy versus surgery, and three involving neoadjuvant treatment followed by surgery or surgery alone versus dCRT were identified. The HR for overall survival was 0·81 (95 per cent confidence interval 0·70 to 0·95; P = 0·008) after neoadjuvant CRT and 0·93 (0·81 to 1·08; P = 0·368) after neoadjuvant chemotherapy. The likelihood of R0 resection was significantly higher after neoadjuvant treatment (CRT: HR 1·15, P = 0·043; chemotherapy: HR 1·16, P = 0·006). Morbidity rates were not increased after neoadjuvant CRT (HR 0·94, P = 0·363) but 30-day mortality was non-significantly higher with combined treatment. Morbidity (HR 1·03, P = 0·638) and mortality (HR 1·04, P = 0·810) rates after neoadjuvant chemotherapy and surgery did not differ from those after surgery alone. None of the RCTs reporting outcome after dCRT demonstrated a significant survival benefit, but treatment-related mortality rates were lower (HR 7·60, P = 0·007) than with neoadjuvant treatment followed by surgery or surgery alone. CONCLUSION: For patients with resectable OSCC, a significant survival benefit for neoadjuvant CRT was evident, with no increase in morbidity rate. dCRT did not demonstrate any survival benefit over other curative strategies. Copyright © 2011 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.


Asunto(s)
Carcinoma de Células Escamosas/terapia , Neoplasias Esofágicas/terapia , Protocolos de Quimioterapia Combinada Antineoplásica , Carcinoma de Células Escamosas/mortalidad , Quimioterapia Adyuvante , Neoplasias Esofágicas/mortalidad , Humanos , Persona de Mediana Edad , Grupo de Atención al Paciente , Radioterapia Adyuvante , Ensayos Clínicos Controlados Aleatorios como Asunto
20.
Br J Surg ; 98(2): 220-7, 2011 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-21165924

RESUMEN

BACKGROUND: Ultrasonic dissection devices have been designed for use in open surgery but it is not certain how they compare with standard surgical techniques. METHODS: This was a multicentre randomized controlled trial comparing ultrasonic dissection with the traditional surgical technique for haemostasis and dissection during left hemicolectomy and total gastrectomy. The primary endpoint was duration of operation; secondary endpoints were blood loss and other intraoperative parameters, and patient outcomes. Performance of the two techniques was rated by surgeons and assistants on a ten-point Likert scale. RESULTS: The analysis included 100 patients in the ultrasonic and 101 in the conventional dissection group. Patient demographics, and clinical and tumour-related parameters were similar in the two groups. There was no significant difference in duration of operation (mean 170 and 178 min in ultrasonic and conventional groups respectively; P = 0·405). Nor were there significant differences in intraoperative blood loss (median 350 and 400 ml respectively; P = 0·882), other intraoperative parameters, oncological or functional outcome. The ultrasonic dissector device was rated one point higher than conventional techniques by the surgeons. CONCLUSION: Use of the ultrasonic dissector in open total gastrectomy and hemicolectomy had no impact on the overall operating time or other endpoints studied. Surgeons preferred the ultrasonic device for dissection.


Asunto(s)
Colectomía/métodos , Disección/métodos , Gastrectomía/métodos , Terapia por Ultrasonido/métodos , Anciano , Pérdida de Sangre Quirúrgica , Femenino , Humanos , Masculino , Variaciones Dependientes del Observador , Calidad de Vida , Resultado del Tratamiento
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