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1.
PLoS One ; 19(1): e0290887, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38236926

RESUMEN

BACKGROUND AND AIMS: Risks of peri- and postoperative complications after bowel surgery in patients with inflammatory bowel disease (IBD) receiving biologics are still discussed controversially. We therefore addressed the safety of different biologics that were applied in our IBD center before surgery. METHODS: Data of IBD patients who underwent bowel resections between 2012 and 2022 at our hospital were analyzed retrospectively. Exposure to biologics was defined by receiving biologics within 12 weeks before resective abdominal surgery. Safety considerations included minor complications, such as infections and wound healing disorders and major complications, e.g., anastomotic insufficiency or abscess formation. RESULTS: A total of 447 IBD patients (334 with Crohn's disease, 113 with ulcerative colitis), 51.9% female, were included and followed for a median follow-up of 45 months [range 0-113]. A total of 73.9% (326/447) were undergoing medical treatment at date of surgery, 61.5% (275/447) were treated with biologics within 3 months and 42.3% (189/447) within 4 weeks before surgery. Most surgeries (97.1%) were planned electively and 67.8% were performed laparoscopically. Major and minor complications occurred in 20.8% (93/447) of patients. Serious complications were rare: Six patients had acute postoperative bleeding, one CD patient developed peritonitis and two CD patients died postoperatively. After adjusting for age, disease duration, disease activity, Montreal classification, and medical treatment at date of surgery, no significant differences were observed regarding complications and exposure to biologics. CONCLUSIONS: This retrospective single center study of 447 IBD patients goes to demonstrate that perioperative use of biologics is not associated with a higher risk of complications.


Asunto(s)
Productos Biológicos , Colitis Ulcerosa , Enfermedad de Crohn , Enfermedades Inflamatorias del Intestino , Humanos , Femenino , Masculino , Estudios Retrospectivos , Productos Biológicos/efectos adversos , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Enfermedades Inflamatorias del Intestino/cirugía , Enfermedad de Crohn/tratamiento farmacológico , Enfermedad de Crohn/cirugía , Factores Biológicos
2.
Z Gastroenterol ; 58(6): 556-563, 2020 Jun.
Artículo en Alemán | MEDLINE | ID: mdl-32450585

RESUMEN

BACKGROUND: Modern, individualised therapies can improve the survival of patients with colorectal cancer. However, not all patients are referred for treatment to a certified colorectal cancer centre, where a tumor board supports the implementation of their therapy in accordance to guidelines. This study examines the feasibility and demand of a structured, online-based, qualified second opinion for patients with colorectal cancer. METHOD: A 15-month pilot study between 2009 and 2011, offered patients with colorectal cancer to obtain a qualified second opinion of a tumour board based on an electronic patient record completed online with the assistance of a case manager. Life-satisfaction levels and quality of life (EORCT QLQ-C30) of the participants has been monitored for a year. RESULTS: In 95 % of the cases, a complete electronic patient record and a second opinion could be generated. Less than half of the participants received their first therapy recommendation from a clinic with a tumour board. The second opinion confirmed the initial medical opinion in 40 % of the cases - 33 % showed a partial and 27 % showed a significant deviation. In case of a deviation, the implementation of the second opinion improved the patients' quality of life. CONCLUSION: Generating an online-based, qualified second opinion by an interdisciplinary tumour board is technically and logistically well feasible. The online-based second opinion could significantly improve the quality of treatment for patients with colorectal cancer in the future and thus improve their quality of life.


Asunto(s)
Neoplasias del Colon , Neoplasias Colorrectales , Humanos , Proyectos Piloto , Calidad de Vida , Derivación y Consulta
3.
Dig Surg ; 33(2): 157-63, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-26824772

RESUMEN

BACKGROUND/AIMS: Recent data suggest that tumors of the right and left colon should be distinguished as they differ in clinical and molecular characteristics. METHODS: A total of 1,319 patients who underwent surgical resection for colon cancer (CC) were investigated. Tumors between the ileocecal valve and the hepatic flexure were classified as right CC (RCC), tumors between the splenic flexure and the rectum as left CC (LCC). RESULTS: RCC revealed a higher cause-specific mortality risk (hazard ratio 1.36, 95% CI 1.10-1.68, p = 0.005) and lower 5-year cause-specific (RCC 64.9%, 95% CI 60.4-69.4, LCC 70.7%, 95% CI 67.2-74.2, p = 0.032) and disease-free (RCC 56.0%, 95% CI 51.5-60.5, LCC 59.9%, 95% CI 56.2-63.6, p = 0.025) survival rates. RCCs were more often microsatellite instable (RCC 37.2%, LCC 13.0%, p < 0.001) and more often showed KRAS (RCC 42.5%, LCC 18.9%, p = 0.001) and BRAF mutations (RCC 26.6%, LCC 3.2%, p < 0.001). CONCLUSION: RCC and LCC differ significantly regarding clinical, histopathological and molecular genetic features and can be considered as distinct entities. The reduced prognosis of RCC may be caused by higher rates of microsatellite instability, KRAS and BRAF mutations.


Asunto(s)
Adenocarcinoma/mortalidad , Adenocarcinoma/cirugía , Colectomía , Colon/patología , Neoplasias del Colon/mortalidad , Neoplasias del Colon/cirugía , Adenocarcinoma/genética , Adenocarcinoma/patología , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/genética , Colon/cirugía , Neoplasias del Colon/genética , Neoplasias del Colon/patología , Femenino , Estudios de Seguimiento , Humanos , Masculino , Inestabilidad de Microsatélites , Persona de Mediana Edad , Mutación , Pronóstico , Estudios Retrospectivos , Análisis de Supervivencia
4.
BMC Surg ; 15: 31, 2015 Mar 21.
Artículo en Inglés | MEDLINE | ID: mdl-25884878

RESUMEN

BACKGROUND: The predilection site of non-occlusive mesenteric ischemia is the right-sided colon. Surgical exploration followed by segmental bowel resection and primary anastomosis or ileostomy is recommended, if vascular interventions are not feasible and conservative treatment fails. We assessed the outcome of patients in this life-threatening condition. METHODS: From a prospective database 58 patients with urgent surgery for acute right-sided colonic ischemia without feasible vascular intervention (as a surrogate for non-occlusive mesenteric ischemia) were identified. Retrospectively the patients' characteristics, reason for ischemia, extent of resection, rate of ileostomy creation, 30 day and one year mortality, and rate of ileostomy-reversal at one year postoperative were assessed. RESULTS: Radiologically mesenteric arteriosclerotic disease was present in 54% of the patients. Vaso-occlusive mesenteric disease was suspected in 15% of the patients, but not confirmed intra-operatively. Ten patients underwent (extended) right-sided hemicolectomy with primary anastomosis (30-days mortality 20%, 1-year mortality 30%). Sixteen patients had (extended) right-sided hemicolectomy with creation of an ileostomy (30-days mortality 44%, 1-year mortality 86%, ostomy reversal in one patient). Twenty-five patients had (sub-) total colectomy with ileostomy creation (30-days mortality 60%, 1-year mortality 72%, ostomy reversal in two patients). Seven patients had exploration only (30-days mortality 86%, 1-year mortality 86%). Overall, the 30-days mortality-rate was 52% and the 1-year mortality-rate was 70%. Only 7% of the patients requiring an ostomy experienced ostomy-reversal. CONCLUSIONS: Patients with urgent surgery for acute right-sided colonic ischemia without feasible vascular intervention have a very high short and long-term mortality. The rate of ostomy-reversal is very low.


Asunto(s)
Colectomía , Colon/irrigación sanguínea , Isquemia/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Colon/cirugía , Femenino , Humanos , Ileostomía , Isquemia/etiología , Isquemia/mortalidad , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Resultado del Tratamiento
6.
Langenbecks Arch Surg ; 400(2): 167-81, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-25681239

RESUMEN

PURPOSE: Surgical site infection (SSI) remains to be one of the most frequent infectious complications following abdominal surgery. Prophylactic intra-operative wound irrigation (IOWI) before skin closure has been proposed to reduce bacterial wound contamination and the risk of SSI. However, current recommendations on its use are conflicting especially concerning antibiotic and antiseptic solutions because of their potential tissue toxicity and enhancement of bacterial drug resistances. METHODS: To analyze the existing evidence for the effect of IOWI with topical antibiotics, povidone-iodine (PVP-I) solutions or saline on the incidence of SSI following open abdominal surgery, a systematic review and meta-analysis of randomized controlled trials (RCTs) was carried out according to the recommendations of the Cochrane Collaboration. RESULTS: Forty-one RCTs reporting primary data of over 9000 patients were analyzed. Meta-analysis on the effect of IOWI with any solution compared to no irrigation revealed a significant benefit in the reduction of SSI rates (OR = 0.54, 95 % confidence Interval (CI) [0.42; 0.69], p < 0.0001). Subgroup analyses showed that this effect was strongest in colorectal surgery and that IOWI with antibiotic solutions had a stronger effect than irrigation with PVP-I or saline. However, all of the included trials were at considerable risk of bias according to the quality assessment. CONCLUSION: These results suggest that IOWI before skin closure represents a pragmatic and economical approach to reduce postoperative SSI after abdominal surgery and that antibiotic solutions seem to be more effective than PVP-I solutions or simple saline, and it might be worth to re-evaluate their use for specific indications.


Asunto(s)
Cavidad Abdominal/cirugía , Cuidados Intraoperatorios/métodos , Infección de la Herida Quirúrgica/prevención & control , Irrigación Terapéutica/métodos , Cavidad Abdominal/fisiopatología , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Laparotomía/efectos adversos , Laparotomía/métodos , Masculino , Ensayos Clínicos Controlados Aleatorios como Asunto , Medición de Riesgo , Infección de la Herida Quirúrgica/epidemiología , Resultado del Tratamiento , Cicatrización de Heridas/fisiología
7.
Gastric Cancer ; 18(2): 314-25, 2015 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-24722800

RESUMEN

BACKGROUND: Neoadjuvant chemotherapy is an accepted standard of care for locally advanced esophagogastric cancer. As only a subgroup benefits, a response-based tailored treatment would be of interest. The aim of our study was the evaluation of the prognostic and predictive value of clinical response in esophagogastric adenocarcinomas. METHODS: Clinical response based on a combination of endoscopy and computed tomography (CT) scan was evaluated retrospectively within a prospective database in center A and then transferred to center B. A total of 686/740 (A) and 184/210 (B) patients, staged cT3/4, cN0/1 underwent neoadjuvant chemotherapy and were then re-staged by endoscopy and CT before undergoing tumor resection. Of 184 patients, 118 (B) additionally had an interim response assessment 4-6 weeks after the start of chemotherapy. RESULTS: In A, 479 patients (70%) were defined as clinical nonresponders, 207 (30%) as responders. Median survival was 38 months (nonresponders: 27 months, responders: 108 months, log-rank, p < 0.001). Clinical and histopathological response correlated significantly (p < 0.001). In multivariate analysis, clinical response was an independent prognostic factor (HR for death 1.4, 95% CI 1.0-1.8, p = 0.032). In B, 140 patients (76%) were nonresponders and 44 (24%) responded. Median survival was 33 months, (nonresponders: 27 months, responders: not reached, p = 0.003). Interim clinical response evaluation (118 patients) also had prognostic impact (p = 0.008). Interim, preoperative clinical response and histopathological response correlated strongly (p < 0.001). CONCLUSION: Preoperative clinical response was an independent prognostic factor in center A, while in center B its prognostic value could only be confirmed in univariate analysis. The accordance with histopathological response was good in both centers, and interim clinical response evaluation showed comparable results to preoperative evaluation.


Asunto(s)
Adenocarcinoma/patología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Endoscopía/métodos , Neoplasias Esofágicas/patología , Unión Esofagogástrica/patología , Neoplasias Gástricas/patología , Tomografía Computarizada por Rayos X/métodos , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/mortalidad , Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Esofágicas/mortalidad , Unión Esofagogástrica/efectos de los fármacos , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Terapia Neoadyuvante , Clasificación del Tumor , Estadificación de Neoplasias , Pronóstico , Estudios Prospectivos , Estudios Retrospectivos , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/mortalidad , Tasa de Supervivencia
8.
Clin Imaging ; 38(6): 845-9, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-25082173

RESUMEN

For this feasibility study, dynamic contrast-enhanced magnetic resonance imaging (dceMRI) was performed preoperatively in 9 patients with histologically proven rectal carcinoma. A total of 41 lymph nodes detected were matched to histopathology. Their contrast enhancement patterns were evaluated using computer-aided analysis and categorized in persistent, plateau, and washout curve type. Highest diagnostic accuracy for detecting malignancy was observed, when less than 31.8% of the voxels within a lymph node demonstrated a washout curve (sensitivity/specificity of 81.8%/89.7%; area under the curve, AUC=0.87). In comparison, conventional size measurements revealed lower AUC of 0.81 (sensitivity/specificity of 75%/72.4%). We conclude that dceMRI might be of diagnostic value for preoperative lymph node staging.


Asunto(s)
Medios de Contraste/farmacocinética , Procesamiento de Imagen Asistido por Computador/métodos , Ganglios Linfáticos/patología , Imagen por Resonancia Magnética/métodos , Cuidados Preoperatorios/métodos , Neoplasias del Recto/patología , Anciano , Estudios de Factibilidad , Femenino , Gadolinio DTPA/farmacocinética , Humanos , Aumento de la Imagen/métodos , Metástasis Linfática/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Reproducibilidad de los Resultados , Sensibilidad y Especificidad
9.
Int J Colorectal Dis ; 29(8): 971-9, 2014 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-24924447

RESUMEN

BACKGROUND: The incidence of colorectal cancer rises disproportionally in aging persons. With a shift towards higher population age in general, an increasing number of older patients require adequate treatment. This study aims to investigate differences between young and elderly patients who undergo resection for colorectal cancer, regarding clinical characteristics, morbidity, and prognosis. METHODS: By retrospective analysis of 6 years (2007 to 2012) of a prospectively documented database, a total of 636 patients were identified who underwent oncological resection for colorectal cancer at our institution. Of this total, all 569 patients with primary colorectal adenocarcinoma were included. Four hundred ten patients were 74 years or younger and 159 were 75 years or older. The median follow-up was 22 months. RESULTS: Older patients had significantly more comorbidities (85 % vs. 56 %, p < 0.001) and a higher ASA score (p < 0.001). The mean length of stay in the hospital was longer (24 vs. 20 days, p = 0.002), as was the length of postoperative intensive care stay (4 vs. 2 days, p = 0.003). However, elderly patients did not have significantly higher rates of intraoperative complications or surgical morbidity. Tumor-specific 2-year survival was 83 ± 4 % for the elderly and 87 ± 2 % for the younger patients, which was not significantly different (p = 0.90). CONCLUSIONS: Long-term outcome after oncologic resection for colorectal cancer does not differ between elderly and younger patients. Age in general should not be considered as a limiting factor for colorectal cancer surgery or tumor-specific prognosis.


Asunto(s)
Neoplasias Colorrectales/epidemiología , Neoplasias Colorrectales/cirugía , Cirugía Colorrectal/estadística & datos numéricos , Distribución por Edad , Factores de Edad , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Neoplasias Colorrectales/patología , Femenino , Estudios de Seguimiento , Alemania/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Atención Perioperativa , Factores de Riesgo
10.
J Clin Invest ; 124(4): 1853-67, 2014 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-24642471

RESUMEN

Members of the miR-34 family are induced by the tumor suppressor p53 and are known to inhibit epithelial-to-mesenchymal transition (EMT) and therefore presumably suppress the early phases of metastasis. Here, we determined that exposure of human colorectal cancer (CRC) cells to the cytokine IL-6 activates the oncogenic STAT3 transcription factor, which directly represses the MIR34A gene via a conserved STAT3-binding site in the first intron. Repression of MIR34A was required for IL-6-induced EMT and invasion. Furthermore, we identified the IL-6 receptor (IL-6R), which mediates IL-6-dependent STAT3 activation, as a conserved, direct miR-34a target. The resulting IL-6R/STAT3/miR-34a feedback loop was present in primary colorectal tumors as well as CRC, breast, and prostate cancer cell lines and associated with a mesenchymal phenotype. An active IL-6R/STAT3/miR-34a loop was necessary for EMT, invasion, and metastasis of CRC cell lines and was associated with nodal and distant metastasis in CRC patient samples. p53 activation in CRC cells interfered with IL-6-induced invasion and migration via miR-34a-dependent downregulation of IL6R expression. In Mir34a-deficient mice, colitis-associated intestinal tumors displayed upregulation of p-STAT3, IL-6R, and SNAIL and progressed to invasive carcinomas, which was not observed in WT animals. Collectively, our data indicate that p53-dependent expression of miR-34a suppresses tumor progression by inhibiting a IL-6R/STAT3/miR-34a feedback loop.


Asunto(s)
Neoplasias Colorrectales/genética , Neoplasias Colorrectales/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Receptores de Interleucina-6/genética , Receptores de Interleucina-6/metabolismo , Factor de Transcripción STAT3/metabolismo , Animales , Línea Celular Tumoral , Neoplasias Colorrectales/patología , Modelos Animales de Enfermedad , Transición Epitelial-Mesenquimal , Retroalimentación Fisiológica , Femenino , Humanos , Masculino , Ratones , Ratones Noqueados , Invasividad Neoplásica , Metástasis de la Neoplasia , Factores de Transcripción de la Familia Snail , Factores de Transcripción/metabolismo
11.
Gastric Cancer ; 17(3): 478-88, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-23996162

RESUMEN

BACKGROUND: Neoadjuvant chemotherapy for locally advanced gastric cancer leads to major histopathological response in less than 30 % of patients. Data on interim endoscopic response assessment do not exist. This exploratory prospective study evaluates early endoscopy after 50 % of the chemotherapy as predictor for later response and prognosis. METHODS: Forty-seven consecutive patients were included (45 resected; 33 R0 resections). All patients received baseline endoscopy and CT scans, after 50 % of their chemotherapy (EGD-1, CT-1) and after completion of chemotherapy (EGD-2, CT-2). Interim endoscopic response (EGD-1) was assessed after having received 50 % (6 weeks) of the planned 12 weeks of neoadjuvant chemotherapy. Post-chemotherapy response was clinically assessed by a combination of CT scan (CT-2) and endoscopy (EGD-2). Histopathological response was determined by a standardized scoring system (Becker criteria). Endoscopic response was defined as a reduction of >75 % of the tumor mass. RESULTS: Twelve patients were responders at EGD-1 and 13 at EGD-2. Nine patients (19.1 %) were clinical responders and 7 patients (15.6 %) were histopathological responders after chemotherapy. Specificity, accuracy, and negative predictive value of the interim EGD-1 for subsequent histopathological response were 31/38 (82 %), 36/47 (76 %), and 31/33 (93 %); and for recurrence or death, 28/30 (93.3 %), 38/47 (80.9 %), and 28/35 (80.0 %). Response at EGD-1 was significantly associated with histopathological response (p = 0.010), survival (p < 0.001), and recurrence-free survival (p = 0.009). CONCLUSIONS: Interim endoscopy after 6 weeks predicts response and prognosis. Therefore, tailoring treatment according to interim endoscopic assessment could be feasible, but the findings of this study should be validated in a larger patient cohort.


Asunto(s)
Antineoplásicos/uso terapéutico , Gastroscopía/métodos , Terapia Neoadyuvante/métodos , Neoplasias Gástricas/terapia , Adulto , Anciano , Antineoplásicos/administración & dosificación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Valor Predictivo de las Pruebas , Pronóstico , Estudios Prospectivos , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Neoplasias Gástricas/patología , Tasa de Supervivencia , Factores de Tiempo , Tomografía Computarizada por Rayos X/métodos , Resultado del Tratamiento
12.
Ann Surg ; 258(5): 775-82; discussion 782-3, 2013 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-23989057

RESUMEN

OBJECTIVES: To define the prognostic value of different histological subtypes of colorectal cancer. BACKGROUND: Most colorectal cancers are classical adenocarcinomas (AC). Less frequent subtypes include mucinous adenocarcinomas (MAC) and signet-ring cell carcinomas (SC). In contrast to established prognostic factors such as TNM and grading, the histological subtype has no therapeutical consequences so far, although it may reflect different biological behavior. METHODS: Between 1982 and 2012, a total of 3479 consecutive patients underwent surgery for primary colorectal cancer (AC, MAC, or SC). Clinical, histopathological, and survival data were analyzed. RESULTS: Of all 3479 patients, histological subtype was AC in 3074 cases (88%), MAC in 375 cases (11%), and SC in 30 cases (0.9%). MAC (51%, P < 0.001) and SC (50%, P = 0.029) occurred more frequently in right-sided tumors than AC (28%). Compared with AC, tumor stages and histological grading were higher in MAC and SC (P < 0.001 for each). Rates of angioinvasion were lower in MAC than in AC (5% vs 9%, P = 0.011). Rates of lymphatic invasion were higher in SC than in AC (67% vs 25%, P < 0.001). Five-year cause-specific survival was 67 ± 1% for AC, 61 ± 3% for MAC, and 21 ± 8% for SC (P < 0.001 for difference between the groups). In multivariable analysis, survival did not differ significantly between AC and MAC after correction for tumor stage. However, SC remained an independent prognostic factor associated with worse survival (hazard ratio = 2.5, 95% confidence interval = 1.6-3.8, P < 0.001). CONCLUSIONS: MAC and SC are histological subtypes of colorectal cancer with different characteristics than classical AC. Both are diagnosed in more advanced tumor stages, but the dismal prognosis of SC seems to be caused by its intrinsic tumor biology.


Asunto(s)
Adenocarcinoma Mucinoso/patología , Carcinoma de Células en Anillo de Sello/patología , Neoplasias Colorrectales/patología , Adenocarcinoma/patología , Adenocarcinoma/cirugía , Adenocarcinoma Mucinoso/cirugía , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células en Anillo de Sello/cirugía , Neoplasias Colorrectales/cirugía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Estadificación de Neoplasias , Pronóstico , Tasa de Supervivencia
13.
Cancer Cell ; 23(1): 93-106, 2013 Jan 14.
Artículo en Inglés | MEDLINE | ID: mdl-23273920

RESUMEN

Loss of p53 is considered to allow progression of colorectal tumors from the adenoma to the carcinoma stage. Using mice with an intestinal epithelial cell (IEC)-specific p53 deletion, we demonstrate that loss of p53 alone is insufficient to initiate intestinal tumorigenesis but markedly enhances carcinogen-induced tumor incidence and leads to invasive cancer and lymph node metastasis. Whereas p53 controls DNA damage and IEC survival during the initiation stage, loss of p53 during tumor progression is associated with increased intestinal permeability, causing formation of an NF-κB-dependent inflammatory microenvironment and the induction of epithelial-mesenchymal transition. Thus, we propose a p53-controlled tumor-suppressive function that is independent of its well-established role in cell-cycle regulation, apoptosis, and senescence.


Asunto(s)
Carcinógenos/toxicidad , Neoplasias Colorrectales/patología , Ganglios Linfáticos/patología , Microambiente Tumoral , Proteína p53 Supresora de Tumor/genética , Adenoma/inducido químicamente , Adenoma/genética , Adenoma/patología , Animales , Carcinoma/inducido químicamente , Carcinoma/genética , Carcinoma/patología , Neoplasias Colorrectales/inducido químicamente , Neoplasias Colorrectales/genética , Modelos Animales de Enfermedad , Ratones , Mutagénesis Sitio-Dirigida , Invasividad Neoplásica/genética , Metástasis de la Neoplasia
15.
Ann Surg ; 256(5): 763-71; discussion 771, 2012 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-23095620

RESUMEN

OBJECTIVES: Individualized risk assessment in patients with UICC stage II colon cancer based on a panel of molecular genetic alterations. BACKGROUND: Risk assessment in patients with colon cancer and localized disease (UICC stage II) is not sufficiently reliable. Development of metachronous metastasis is assumed to be governed largely by individual tumor genetics. METHODS: Fresh frozen tissue from 232 patients (T3-4, N0, M0) with complete tumor resection and a median follow-up of 97 months was analyzed for microsatellite stability, KRAS exon 2, and BRAF exon 15 mutations. Gene expression of the WNT-pathway surrogate marker osteopontin and the metastasis-associated genes SASH1 and MACC1 was determined for 179 patients. The results were correlated with metachronous distant metastasis risk (n = 22 patients). RESULTS: Mutations of KRAS were detected in 30% patients, mutations of BRAF in 15% patients, and microsatellite instability in 26% patients. Risk of recurrence was associated with KRAS mutation (P = 0.033), microsatellite stable tumors (P = 0.015), decreased expression of SASH1 (P = 0.049), and increased expression of MACC1 (P < 0.001). MACC1 was the only independent parameter for recurrence prediction (hazard ratio: 6.2; 95% confidence interval: 2.4-16; P < 0.001). Integrative 2-step cluster analysis allocated patients into 4 groups, according to their tumor genetics. KRAS mutation, BRAF wild type, microsatellite stability, and high MACC1 expression defined the group with the highest risk of recurrence (16%, 7 of 43), whereas BRAF wild type, microsatellite instability, and low MACC1 expression defined the group with the lowest risk (4%, 1 of 26). CONCLUSIONS: MACC1 expression predicts development of metastases, outperforming microsatellite stability status, as well as KRAS/BRAF mutation status.


Asunto(s)
Neoplasias del Colon/genética , Neoplasias del Colon/patología , Metástasis de la Neoplasia/genética , Factores de Transcripción/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/análisis , Codón , Interpretación Estadística de Datos , Exones , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Masculino , Inestabilidad de Microsatélites , Persona de Mediana Edad , Mutación , Recurrencia Local de Neoplasia/genética , Estadificación de Neoplasias , Osteopontina/genética , Valor Predictivo de las Pruebas , Proteínas Proto-Oncogénicas/genética , Proteínas Proto-Oncogénicas B-raf/genética , Proteínas Proto-Oncogénicas p21(ras) , Medición de Riesgo , Tasa de Supervivencia , Transactivadores , Proteínas Supresoras de Tumor/genética , Proteínas ras/genética
16.
Int J Colorectal Dis ; 27(6): 789-95, 2012 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-22249437

RESUMEN

PURPOSE: For treatment of rectal prolapse, abdominal approaches are generally offered to younger patients, whereas perineal, less invasive procedures are considered more beneficial in the elderly. The aim of this study was to analyze whether laparoscopic resection rectopexy (LRR) is suitable for older patients. PATIENTS/METHODS: Patients who received LRR for rectal prolapse were selected from a prospective laparoscopic colorectal surgery database. Perioperative and long-term outcome were compared between patients <75 years old (group A) and ≥75 years old (group B). RESULTS: Of 154 patients, 111 were in group A and 43 in group B. There was one conversion that occurred in group B. Overall mortality rate was 1.3% (n = 2). Both patients were in group B (group B, 4.7%; p = 0.079). Differences in major and minor complications between the groups were not significant. Rates of improvement for incontinence were 62.7% (group A) and 66.7% (group B; p = 0.716); for constipation, the rates were 78.9% (group A) and 73.3% (group B; p = 0.832). All recurrences occurred in group A (n = 10; overall, 10.3%; group A, 13%). After exclusion of patients who had previously received perineal prolapse surgery, recurrence rate was 3.3% overall (group A, 4.3%). CONCLUSIONS: This study supports the benefits of LRR for rectal prolapse in elderly patients. Age per se is not a contraindication for LRR. Elderly patients encounter complications slightly more frequently (although not statistically significant) than younger patients. Therefore, a very careful patient selection in the elderly is of paramount importance. However, the long-term outcome does not seem to differ between younger and elderly patients.


Asunto(s)
Procedimientos Quirúrgicos del Sistema Digestivo/métodos , Laparoscopía , Prolapso Rectal/cirugía , Recto/cirugía , Anciano , Estreñimiento/etiología , Demografía , Incontinencia Fecal/etiología , Estudios de Seguimiento , Alemania/epidemiología , Hospitalización , Humanos , Tiempo de Internación , Persona de Mediana Edad , Complicaciones Posoperatorias/etiología , Prolapso Rectal/mortalidad , Resultado del Tratamiento
17.
Langenbecks Arch Surg ; 396(6): 857-66, 2011 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-21713594

RESUMEN

PURPOSE: Correct diagnosis, surgical treatment, and perioperative management of patients with esophageal carcinoma remain crucial for prognosis within multimodal treatment procedures. This study aims to achieve a consensus regarding current management strategies in esophageal cancer by questioning a panel of experts from the German Advanced Surgical Treatment Study (GAST) group, comprised of 9 centers specialized in esophageal surgery, with a combined total of >220 esophagectomies per year. MATERIALS AND METHODS: The Delphi method, a systematic and interactive, evidence-based approach, was used to obtain consensus statements from the GAST group regarding ambiguities and disparities in diagnosis, patient selection, surgical technique, and perioperative management of patients with esophageal carcinoma. After four rounds of surveys, agreement was measured by Likert scales and defined as full (100% agreement), near (≥66.6% agreement), or no consensus (<66.6% agreement). RESULTS: Full or near consensus was obtained for essential aspects of esophageal cancer staging, proper surgical technique, perioperative management and indication for primary surgery, and neoadjuvant treatment or palliative treatment. No consensus was achieved regarding acceptability of minimally invasive technique and postoperative nutrition after esophagectomy. CONCLUSION: The GAST consensus statement represents a position paper for treatment of patients with esophageal carcinoma which both contributes to the development of clinical treatment guidelines and outlines topics in need of further clinical studies.


Asunto(s)
Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/cirugía , Esofagectomía/métodos , Consenso , Técnica Delphi , Alemania , Humanos , Terapia Neoadyuvante , Estadificación de Neoplasias , Cuidados Paliativos , Selección de Paciente , Periodo Perioperatorio , Pronóstico
18.
Langenbecks Arch Surg ; 396(6): 851-5, 2011 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-21562864

RESUMEN

INTRODUCTION: A variety of surgical strategies have been suggested and many surgical techniques, both abdominal and perineal, have been introduced for treatment of rectal prolapse. All these techniques and approaches are based on the attempt to restore the normal anatomy and physiologic function. METHODS: In 1992, Berman et al. published the first laparoscopically performed rectopexy. Meanwhile, many different minimally invasive procedures have been described. Throughout the past century, more than 100 different surgical techniques have been introduced to treat patients with rectal prolapse. Unfortunately, there is still lack of one generally accepted standard technique for the surgical treatment of rectal prolapse. RESULTS AND DISCUSSION: Our current data strongly supports laparoscopic resection rectopexy to be a safe, fast, and very effective procedure to improve function in patients with rectal prolapse. More evaluations of long-term outcome are needed that focus on each particular laparoscopic procedure to adequately compare different techniques. The indication to perform a laparoscopic resection rectopexy in patients with a previous perineal procedure and a recurrent prolapse should be stated critically because these patients seem to have a high risk to develop yet another recurrence.


Asunto(s)
Laparoscopía/métodos , Procedimientos Quirúrgicos Mínimamente Invasivos , Prolapso Rectal/cirugía , Anciano , Anciano de 80 o más Años , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Posicionamiento del Paciente , Complicaciones Posoperatorias , Recurrencia , Encuestas y Cuestionarios , Resultado del Tratamiento
20.
Surg Endosc ; 24(10): 2401-6, 2010 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-20177911

RESUMEN

BACKGROUND: Many different techniques to treat rectal prolapse have been introduced. Laparoscopic resection rectopexy has been shown to entail benefits regarding both perioperative results and short-term outcome, whereas data for long-term outcome are scarce. METHODS: Between 1993 and 2008, all laparoscopic resection rectopexies for rectal prolapse II° or III° were selected from a prospective laparoscopic colorectal surgery database. We analyzed demographic, perioperative, and follow-up results. We defined two periods (1993-2000 and 2001-2008) for comparison of data. Long-term follow-up was obtained by sending questionnaires to all patients. Evaluation included constipation, incontinence, and recurrence of prolapse. RESULTS: Between January 1993 and November 2008, we performed 152 laparoscopic resection rectopexies for rectal prolapse. Median age was 64.1 years (± 14.6). Conversion rate was 0.7% (1), mean operation time was 204 (± 65.3) min, and was significantly shorter in the second period compared with the first (P < 0.0001). Mortality was 0.7% (n = 1). Complication rates were 4% (n = 6; major) and 19.2% (n = 29; minor), respectively. Mean length of hospital stay was 11.3 (± 6.4) days and was significantly shorter in the second period compared with the first period (P < 0.0001). Mean time of follow-up was 47.7 (± 41.6) months. Improvement or complete elimination of constipation was stated by 81.3% (65), and improvement or elimination of incontinence was stated by 67.3% (72). Overall recurrence rate was 11.1% (n = 10) with a rate of 5.6% (n = 5) for a 5-year period. Of those patients with previous perineal surgery for rectal prolapse, 53.8% (7/13) experienced recurrent prolapse after laparoscopic resection rectopexy in contrast to 3.9% (3/77) of patients without previous perineal prolapse surgery (P < 0.0001). CONCLUSIONS: Our data support the benefits of laparoscopic resection rectopexy for rectal prolapse regarding both perioperative results and long-term functional outcome. Preceding perineal or open abdominal operations have an impact on recurrence after laparoscopic resection rectopexy.


Asunto(s)
Laparoscopía , Prolapso Rectal/cirugía , Femenino , Humanos , Laparoscopía/efectos adversos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias , Prolapso Rectal/patología , Recto/cirugía , Reoperación , Resultado del Tratamiento
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