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

RESUMEN

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


Asunto(s)
Trasplante de Riñón , Humanos , Trasplante de Riñón/efectos adversos , Trasplante de Riñón/métodos , Estudios Retrospectivos , Sistema del Grupo Sanguíneo ABO , Incompatibilidad de Grupos Sanguíneos , Factores de Riesgo , Rechazo de Injerto , Supervivencia de Injerto , Donadores Vivos
2.
Anasthesiol Intensivmed Notfallmed Schmerzther ; 58(11-12): 660-664, 2023 Dec.
Artículo en Alemán | MEDLINE | ID: mdl-38056445

RESUMEN

We report the perioperative course of a 47-year-old patient who underwent a two-stage liver resection for bilobar metastatic colorectal carcinoma. The respiratory asymptomatic patient was tested positive for SARS-CoV-2 by PCR detection one day before the second surgical procedure. Postoperatively, the patient suffered cardiovascular arrest on postoperative day 8 and died despite immediately initiated resuscitative measures. With an initial clinical suspicion of vascular liver failure, postmortem pathologic examination revealed the underlying cause of death to be COVID-19-related myocarditis with acute right heart failure. Individual multidisciplinary risk assessment should be considered very critically when deviating from the "7-week rule" because the benefit is difficult to objectify, even in oncologic patients.


Asunto(s)
COVID-19 , Neoplasias Colorrectales , Insuficiencia Cardíaca , Hepatectomía , Neoplasias Hepáticas , Miocarditis , Humanos , Persona de Mediana Edad , COVID-19/diagnóstico , COVID-19/mortalidad , Resultado Fatal , Hígado/cirugía , SARS-CoV-2 , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/cirugía , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/cirugía , Infecciones Asintomáticas/mortalidad , Hepatectomía/métodos , Hepatectomía/mortalidad , Miocarditis/etiología , Miocarditis/mortalidad , Insuficiencia Cardíaca/etiología , Insuficiencia Cardíaca/mortalidad
3.
J Clin Invest ; 134(5)2023 Dec 28.
Artículo en Inglés | MEDLINE | ID: mdl-38153787

RESUMEN

Metastasized colorectal cancer (CRC) is associated with a poor prognosis and rapid disease progression. Besides hepatic metastasis, peritoneal carcinomatosis is the major cause of death in Union for International Cancer Control (UICC) stage IV CRC patients. Insights into differential site-specific reconstitution of tumor cells and the corresponding tumor microenvironment are still missing. Here, we analyzed the transcriptome of single cells derived from murine multivisceral CRC and delineated the intermetastatic cellular heterogeneity regarding tumor epithelium, stroma, and immune cells. Interestingly, we found an intercellular site-specific network of cancer-associated fibroblasts and tumor epithelium during peritoneal metastasis as well as an autologous feed-forward loop in cancer stem cells. We furthermore deciphered a metastatic dysfunctional adaptive immunity by a loss of B cell-dependent antigen presentation and consecutive effector T cell exhaustion. Furthermore, we demonstrated major similarities of this murine metastatic CRC model with human disease and - based on the results of our analysis - provided an auspicious site-specific immunomodulatory treatment approach for stage IV CRC by intraperitoneal checkpoint inhibition.


Asunto(s)
Fibroblastos Asociados al Cáncer , Neoplasias del Colon , Neoplasias Colorrectales , Neoplasias Primarias Secundarias , Humanos , Animales , Ratones , Neoplasias Colorrectales/genética , Inmunidad Adaptativa , Presentación de Antígeno , Microambiente Tumoral/genética
4.
Front Immunol ; 13: 908449, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35844581

RESUMEN

More than half of all patients with colorectal cancer (CRC) develop distant metastasis and, depending on the local stage of the primary tumor, up to 48% of patients present peritoneal carcinomatosis (PC). PC is often considered as a widespread metastatic disease, which is almost resistant to current systemic therapies like chemotherapeutic and immunotherapeutic regimens. Here we could show that tumor cells of PC besides being senescent also exhibit stem cell features. To investigate these surprising findings in more detail, we established a murine model based on tumor organoids that resembles the clinical setting. In this murine orthotopic transplantation model for peritoneal carcinomatosis, we could show that the metastatic site in the peritoneum is responsible for senescence and stemness induction in tumor cells and that induction of senescence is not due to oncogene activation or therapy. In both mouse and human PC, senescence is associated with a senescence-associated secretory phenotype (SASP) influencing the tumor microenvironment (TME) of PC. SASP factors are able to induce a senescence phenotype in neighbouring cells. Here we could show that SASP leads to enhanced immunosenescence in the TME of PC. Our results provide a new immunoescape mechanism in PC explaining the resistance of PC to known chemo- and immunotherapeutic approaches. Therefore, senolytic approaches may represent a novel roadmap to target this terminal stage of CRC.


Asunto(s)
Inmunosenescencia , Neoplasias Peritoneales , Animales , Humanos , Ratones , Peritoneo/patología , Fenotipo , Microambiente Tumoral
5.
World J Gastrointest Oncol ; 12(8): 903-917, 2020 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-32879667

RESUMEN

BACKGROUND: Cytoreductive surgery (CRS) in combination with hyperthermic intraperitoneal chemotherapy (HIPEC) improves patient survival in colorectal cancer (CRC) with peritoneal carcinomatosis (PC). Commonly used cytotoxic agents include mitomycin C (MMC) and oxaliplatin. Studies have reported varying results, and the evidence for the choice of the HIPEC agent and uniform procedure protocols is limited. AIM: To evaluate therapeutic benefits and complications of CRS + MMC vs oxaliplatin HIPEC in patients with peritoneal metastasized CRC as well as prognostic factors. METHODS: One hundred and two consecutive patients who had undergone CRS and HIPEC for CRC PC between 2007 and 2019 at the Medical Center of the University Freiburg regarding interdisciplinary cancer conference decision were retrospectively analysed. Oxaliplatin and MMC were used in 68 and 34 patients, respectively. Each patient's demographics and tumour characteristics, operative details, postoperative complications and survival were noted. Complications were stratified and graded using Clavien/Dindo analysis. Prognostic outcome factors were identified using univariate and multivariate analysis of survival. RESULTS: The two groups did not differ significantly regarding baseline characteristics. We found no difference in median overall survival between MMC and oxaliplatin HIPEC. Regarding postoperative complications, patients treated with oxaliplatin HIPEC suffered increased complications (66.2% vs 35.3%; P = 0.003), particularly intestinal atony, intraabdominal infections and urinary tract infection, and had a prolonged intensive care unit stay compared to the MMC group (7.2 d vs 4.4 d; P = 0.035). Regarding univariate analysis of survival, we found primary tumour factors, nodal positivity and resection margins to be of prognostic value as well as peritoneal cancer index (PCI)-score and the completeness of cytoreduction regarding peritoneal carcinomatosis. Multivariate analysis of survival confirmed primary distant metastasis and primary tumour resection status to have a significant impact on survival and likewise peritoneal cancer index-scoring regarding peritoneal carcinomatosis. CONCLUSION: In this single-institution retrospective review of patients undergoing CRS with either oxaliplatin or MMC HIPEC, overall survival was not different, though oxaliplatin was associated with a higher postoperative complication rate, indicating treatment favourably with MMC. Further studies comparing HIPEC regimens would improve evidence-based decision-making.

6.
Langenbecks Arch Surg ; 405(6): 833-842, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-32705344

RESUMEN

BACKGROUND: In end-stage renal transplant recipients with autosomal-dominant polycystic kidney disease (ADPKD), the imperative, optimal timing, and technique of native nephrectomy remains under discussion. The Freiburg Transplant Center routinely performs a simultaneous ipsilateral nephrectomy. METHODS: From April 1998 to May 2017, we retrospectively analyzed 193 consecutive ADPKD recipients, receiving per protocol simultaneous ipsilateral nephrectomy and compared morbidity, mortality, and outcome with 193 non-ADPKD recipients of a matched pair control. RESULTS: The incidence of surgical complications was similar with respect to severe medical, surgical, urological, vascular, and wound-related complications as well as reoperation rates and 30-day mortality. Intraoperative blood transfusions were required more often in the ADPKD (22.8%) compared with the control group (6.7%; p < 0.0001). Early postoperative urinary tract infections occurred more frequent (ADPKD 40.4%/control 29.0%; p = 0.0246). Time of surgery was prolonged by 30 min (ADPKD 169 min; 95%CI 159.8-175.6 min/control 139 min; 95%CI 131.4-145.0 min; p < 0.0001). One-year patient (ADPKD 96.4%/control 95.8%; p = 0.6537) and death-censored graft survival (ADPKD 94.8%/control 93.7%; p = 0.5479) were comparable between both groups. CONCLUSIONS: With respect to morbidity and mortality, per protocol, simultaneous native nephrectomy is a safe procedure. Especially in asymptomatic ADPKD KTx recipients, the number of total operations can be reduced and residual diuresis preserved up until transplantation. In living donation, even preemptive transplantation is possible.


Asunto(s)
Trasplante de Riñón , Nefrectomía/métodos , Riñón Poliquístico Autosómico Dominante/cirugía , Transfusión Sanguínea/estadística & datos numéricos , Femenino , Alemania/epidemiología , Supervivencia de Injerto , Humanos , Incidencia , Masculino , Análisis por Apareamiento , Persona de Mediana Edad , Tempo Operativo , Riñón Poliquístico Autosómico Dominante/mortalidad , Complicaciones Posoperatorias/epidemiología , Estudios Retrospectivos , Infecciones Urinarias/epidemiología
7.
Int J Colorectal Dis ; 34(2): 337-345, 2019 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-30483864

RESUMEN

OBJECTIVE: To examine pasireotide's effect on intestinal anastomotic healing under physiological conditions and following preoperative whole-body irradiation. MATERIAL AND METHODS: Forty-five male Wistar rats received an ileoileal end-to-end anastomosis. Group 1 (Co, n = 9) served as control. Group 2 (SOM, n = 10) received pasireotide (60 mg/kg) 6 days preoperatively. Group 3 (R-Co, n = 13) was subjected to 8 Gy whole-body irradiation 4 days preoperatively. Finally, group 4 (R-SOM, n = 13) received pasireotide 6 days preoperatively and whole-body irradiation 4 days preoperatively. On postoperative day 4, anastomotic bursting pressure, histology, IGF-1 staining, and collagen density were examined. RESULTS: Mortality was higher in irradiated animals (30.8% vs. 5.3%, p = 0.021), and anastomotic bursting pressure was significantly lower (median, R-Co = 83 mmHg; R-SOM = 101 mmHg; Co = 149.5 mmHg; SOM = 169 mmHg). Inflammation measured by leukocyte infiltration following irradiation was reduced (p = 0.023), and less collagen was observed, though this was not statistically significant. Bursting pressure did not significantly differ between Co and SOM and between R-Co and R-SOM animals respectively. Semi-quantitative scoring of IGF-1, fibroblast bridging, or collagen density did not reveal significant differences among the groups. CONCLUSION: Whole-body irradiation decreases the quality of intestinal anastomotic wound healing and increases mortality. Pasireotide does not significantly lessen this detrimental effect.


Asunto(s)
Intestinos/patología , Intestinos/cirugía , Somatostatina/análogos & derivados , Irradiación Corporal Total , Cicatrización de Heridas/efectos de los fármacos , Anastomosis Quirúrgica , Animales , Glucemia/metabolismo , Peso Corporal/efectos de los fármacos , Causas de Muerte , Modelos Animales de Enfermedad , Granulocitos/metabolismo , Inyecciones , Factor I del Crecimiento Similar a la Insulina/metabolismo , Masculino , Complicaciones Posoperatorias/etiología , Presión , Ratas Wistar , Somatostatina/administración & dosificación , Somatostatina/farmacología , Adherencias Tisulares/patología
8.
BMC Surg ; 18(1): 89, 2018 Oct 29.
Artículo en Inglés | MEDLINE | ID: mdl-30373582

RESUMEN

BACKGROUND: The indication for hepatic resection (HR) in patients suffering from liver metastases (LM) other than colorectal and neuroendocrine tumors is one focus of current multidisciplinary, oncologic considerations. This study retrospectively analyzes outcome after HR for non-colorectal, non-neuroendocrine (NCNNE) LM in the absence of distant or extrahepatic metastases. METHODS: We included 100 consecutive patients undergoing HR for isolated NCNNE LM from a prospective database in our institution, including postoperative follow-up. Primary tumors were of mesodermal origin in 44%, of ectodermal origin in 29% and of entodermal origin in 27%. Survival analysis was performed by univariate and multivariable methods. Mean follow-up after hepatic surgery was 3.6 years (0.25-16). RESULTS: Median age at the time of HR was 59.5 years. Kaplan-Meier-estimated survival after liver resection was 56.8%, 34.3% and 24.5% after 5, 10 and 15 years, respectively. Univariate analysis after HR revealed residual disease (hepatic or primary; p = 0.02), female gender (p = 0.013), entodermal origin (p = 0.009) and early onset of metastatic disease (≤24 months, p = 0.002), as negative prognostic factors. Multivariable survival analysis confirmed residual disease, female gender, entodermal embryologic origin and early onset of metastatic disease (≤24 months) as independent negative prognostic factors. CONCLUSION: Overall outcome after HR of NCNNE LM results in acceptable long-term outcome. Although individual decision-making today mostly relies on clinical experience for this type of disease, risk factors derived from the embryologic origin of the tumor might help in patient selection.


Asunto(s)
Hepatectomía/métodos , Neoplasias Hepáticas/cirugía , Neoplasias/patología , Adulto , Anciano , Femenino , Humanos , Neoplasias Hepáticas/secundario , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Estudios Retrospectivos , Análisis de Supervivencia , Resultado del Tratamiento
9.
Dig Liver Dis ; 50(10): 1088-1092, 2018 10.
Artículo en Inglés | MEDLINE | ID: mdl-30055964

RESUMEN

INTRODUCTION: In unresectable patients with metastatic colorectal cancer (CRC), the site of the primary is a strong prognostic factor warranting major adjustments in palliative medical treatment. Initial results suggested that the site of CRC influences prognosis after curative resection of colorectal liver metastases (CLM). In this study, we evaluated outcome after resection of isolated CLM with regard to the location of the primary. METHODS: 221 patients with macroscopically complete resection of CLM and no known extrahepatic disease were identified. 63 patients had right-sided and 158 had left-sided CRC. Tumors of the transverse colon and rectum were excluded. Survival was evaluated using the Kaplan-Meier method. RESULTS: Characteristics of CLM, primary tumor stage and chemotherapeutic regimens were not significantly different between the two groups. Kaplan-Meier five-year survival was comparable (41%) in patients with right- or left-sided CRC (p = 0.64). Microscopic resection margin, number of liver metastases, age and nodal status but not the site of the primary tumor significantly influenced survival. CONCLUSION: The site of the colorectal primary in this well-defined group of patients after resection of isolated CLM did not prove to be of significant prognostic value. Whether the primary tumor in CLM is located on the left side or the right should not preclude patients from surgery.


Asunto(s)
Colon/patología , Neoplasias Colorrectales/patología , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/cirugía , Hígado/patología , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias Colorrectales/mortalidad , Femenino , Alemania/epidemiología , Hepatectomía/métodos , Humanos , Masculino , Márgenes de Escisión , Persona de Mediana Edad , Cuidados Paliativos , Pronóstico , Análisis de Supervivencia
10.
Surg Case Rep ; 4(1): 50, 2018 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-29845578

RESUMEN

BACKGROUND: Primary hernias in the triangle of Grynfeltt are very rare and therefore pose a difficulty in diagnosis and treatment. Due to the lack of systematic studies, the surgical approach must be chosen individually for each patient. Here, we describe an easy and safe surgical approach. CASE PRESENTATION: We report the case of a 53-year-old male patient with a history of mental disability and pronounced scoliosis, who presented with a Grynfeltt-Lesshaft hernia with protrusion of the ascending colon and the right ureter. The hernia was repaired via a dorsal, extraperitoneal approach. The hernia gap with a diameter of approximately 1 cm was closed with insertion of a 6.4 × 6.4 cm PROCEED™ VENTRAL PATCH (Ethicon, Norderstedt, Germany). The operating time was 33 min and the patient was discharged the next day and showed no signs of recurrence at 1-year follow up. CONCLUSION: The technique described here is favorable because it requires very little dissection of the surrounding tissue and no trans-/intraabdominal dissection. The technique was chosen in this particular case to guarantee a fast postoperative recovery and prompt hospital discharge.

12.
BMC Surg ; 15: 108, 2015 Oct 06.
Artículo en Inglés | MEDLINE | ID: mdl-26444274

RESUMEN

BACKGROUND: Clinical data indicate that laparoscopic surgery reduces postoperative inflammatory response and benefits patient recovery. Little is known about the mechanisms involved in reduced systemic and local inflammation and the contribution of reduced trauma to the abdominal wall and the parietal peritoneum. METHODS: Included were 61 patients, who underwent elective colorectal resection without intraabdominal complications; 17 received a completely laparoscopic, 13 a laparoscopically- assisted procedure and 31 open surgery. Local inflammatory response was quantified by measurement of intraperitoneal leukocytes and IL-6 levels during the first 4 days after surgery. RESULTS: There was no statistical difference between the groups in systemic inflammatory parameters and intraperitoneal leukocytes. Intraperitoneal interleukin-6 was significantly lower in the laparoscopic group than in the laparoscopically-assisted and open group on postoperative day 1 (26.16 versus 43.25 versus 40.83 ng/ml; p = 0.001). No difference between the groups was recorded on POD 2-4. Intraperitoneal interleukin-6 showed a correlation with duration of hospital stay on POD 1 (0.233, p = 0.036), but not on POD 2-4. Patients who developed a surgical wound infection showed higher levels of intraperitoneal interleukin-6 on postoperative day 2-4 (POD 2: 42.56 versus 30.02 ng/ml, p = 0.03), POD 3: 36.52 versus 23.62 ng/ml, p = 0.06 and POD 4: 34.43 versus 19.99 ng/ml, p = 0.046). Extraabdominal infections had no impact. CONCLUSION: The analysis shows an attenuated intraperitoneal inflammatory response on POD 1 in completely laparoscopically-operated patients, associated with a quicker recovery. This effect cannot be observed in patients, who underwent a laparoscopically-assisted or open procedure. Factors inflicting additional trauma to the abdominal wall and parietal peritoneum promote the intraperitoneal inflammation process.


Asunto(s)
Colectomía/efectos adversos , Enfermedades del Colon/cirugía , Laparoscopía/efectos adversos , Infección de la Herida Quirúrgica/etiología , Adulto , Procedimientos Quirúrgicos Electivos/efectos adversos , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Periodo Posoperatorio , Estudios Retrospectivos , Infección de la Herida Quirúrgica/diagnóstico
13.
Eur J Pediatr Surg ; 25(3): 269-76, 2015 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-24819244

RESUMEN

AIM: The aim of the article is to investigate a new anastomotic technique compared with standardized intestinal anastomotic procedures. MATERIALS AND METHODS: A total of 32 male Wistar rats were randomized to three groups. In the Experimental Group (n = 10), the new double 90 degrees inversely rotated anastomosis was used, in the End Group (n = 10) a single-layer end-to-end anastomosis, and in the Side Group (n = 12) a single-layer side-to-side anastomosis. All anastomoses were done using interrupted sutures. On postoperative day 4, rats were relaparotomized. Bursting pressure, hydroxyproline concentration, a semiquantitative adhesion score and two histological anastomotic healing scores (mucosal healing according to Chiu and overall anastomotic healing according to Verhofstad) were collected. Most data are presented as median (range). p < 0.05 was considered significant. RESULTS: Anastomotic insufficiency occurred only in one rat of the Side Group. Median bursting pressure in the Experimental Group was 105 mm Hg (range = 72-161 mm Hg), significantly higher in the End Group (164 mm Hg; range = 99-210 mm Hg; p = 0.021) and lower in the Side Group by trend (81 mm Hg; range = 59-122 mm Hg; p = 0.093). Hydroxyproline concentration did not differ significantly in between the groups. The adhesion score was 2.5 (range = 1-3) in the Experimental Group, 2 (range = 1-2) in the End Group, but there were significantly more adhesions in the Side Group (range = 3-4); p = 0.020 versus Experimental Group, p < 0.001 versus End Group. The Chiu Score showed the worst mucosal healing in the Experimental Group. The overall Verhofstad Score was significantly worse (mean = 2.032; standard deviation [SD] = 0.842) p = 0.031 and p = 0.002 in the Experimental Group, compared with the Side Group (mean = 1.729; SD = 0.682) and the End Group (mean = 1.571; SD = 0.612). CONCLUSION: The new anastomotic technique is feasible and did not show any relevant complication. Even though it was superior to the side-to-side anastomosis by trend with respect to functional stability, mucosal healing surprisingly showed the worst results. Classical end-to-end anastomosis still seems to be the best choice regarding structural and functional anastomotic stability.


Asunto(s)
Anastomosis Quirúrgica/métodos , Intestinos/cirugía , Animales , Estudios de Factibilidad , Hidroxiprolina/metabolismo , Mucosa Intestinal/fisiología , Intestinos/patología , Intestinos/fisiología , Masculino , Distribución Aleatoria , Ratas Wistar , Técnicas de Sutura , Resistencia a la Tracción , Adherencias Tisulares/patología , Cicatrización de Heridas
14.
J Gastrointest Surg ; 18(12): 2149-54, 2014 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-25326126

RESUMEN

BACKGROUND: To examine bowel wall edema development in laparoscopic and open major visceral surgery. METHODS: In a prospective study, 47 consecutively operated patients with gastric and pancreatic resections were included. Twenty-seven patients were operated in a conventional open procedure (open group) and 20 in a laparoscopic fashion (lap group). In all procedures, a small jejunal segment was resected during standard preparation, of which we measured the dry-wet ratio. Furthermore, HE staining was performed for measuring of bowel wall thickness and edema assessment. RESULTS: Mean value (±std) of dry-wet ratio was significantly lower in the open than in the lap group (0.169 ± 0.017 versus 0.179 ± 0.015; p = 0.03) with the same amount of fluid administration in both groups and a longer infusion interval during laparoscopic surgery. Subgroup analyses (only pancreatic resections) still showed similar results. Histologic examination depicted a significantly larger bowel wall thickness in the open group. CONCLUSIONS: Laparoscopic surgery does not seem to lead to the bowel wall edema observed to occur in open surgery regardless of the degree of intravenous fluid administration, thus supporting its use even in major visceral surgery.


Asunto(s)
Edema/diagnóstico , Complicaciones Intraoperatorias/diagnóstico , Yeyuno/patología , Laparoscopía , Laparotomía , Edema/etiología , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Pancreatectomía , Estudios Prospectivos
15.
Eur Surg Res ; 53(1-4): 73-85, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-25139553

RESUMEN

PURPOSE: This investigation focuses on the physiological characteristics of gene transcription of intestinal tissue following anastomosis formation. METHODS: In eight rats, end-to-end ileo-ileal anastomoses were performed (n = 2/group). The healthy intestinal tissue resected for this operation was used as a control. On days 0, 2, 4 and 8, 10-mm perianastomotic segments were resected. Control and perianastomotic segments were examined with an Affymetrix microarray chip to assess changes in gene regulation. Microarray findings were validated using real-time PCR for selected genes. In addition to screening global gene expression, we identified genes intensely regulated during healing and also subjected our data sets to an overrepresentation analysis using the Gene Ontology (GO) and Kyoto Encyclopedia for Genes and Genomes (KEGG). RESULTS: Compared to the control group, we observed that the number of differentially regulated genes peaked on day 2 with a total of 2,238 genes, decreasing by day 4 to 1,687 genes and to 1,407 genes by day 8. PCR validation for matrix metalloproteinases-3 and -13 showed not only identical transcription patterns but also analogous regulation intensity. When setting the cutoff of upregulation at 10-fold to identify genes likely to be relevant, the total gene count was significantly lower with 55, 45 and 37 genes on days 2, 4 and 8, respectively. A total of 947 GO subcategories were significantly overrepresented during anastomotic healing. Furthermore, 23 overrepresented KEGG pathways were identified. CONCLUSION: This study is the first of its kind that focuses explicitly on gene transcription during intestinal anastomotic healing under standardized conditions. Our work sets a foundation for further studies toward a more profound understanding of the physiology of anastomotic healing.


Asunto(s)
Anastomosis Quirúrgica , Mucosa Intestinal/metabolismo , Intestinos/cirugía , Cicatrización de Heridas/fisiología , Animales , Perfilación de la Expresión Génica , Ontología de Genes , Masculino , Análisis de Secuencia por Matrices de Oligonucleótidos , Reacción en Cadena de la Polimerasa , Distribución Aleatoria , Ratas Wistar
16.
Int J Colorectal Dis ; 29(4): 469-75, 2014 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-24468796

RESUMEN

PURPOSE: Clinical data indicate that laparoscopic surgery has a beneficial effect on intestinal wound healing and is associated with a lower incidence of anastomotic leakage. This observation is based on weak evidence, and little is known about the impact of intraoperative parameters during laparoscopic surgery, e.g., temperature and humidity. METHODS: A small-bowel anastomosis was formed in rats inside an incubator, in an environment of stable humidity and temperature. Three groups of ten Wistar rats were operated: a control group (G1) in an open surgical environment and two groups (G2 and G3) in the incubator at a humidity of 60 % and a temperature of 30 and 37 °C (G2 and G3, respectively). After 4 days, bursting pressure and hydroxyproline concentration of the anastomosis were analyzed. The tissue was histologically examined. Serum levels of C-reactive-protein (CRP) were measured. RESULTS: No significant changes were seen in the evaluation of anastomotic stability. Bursting pressure was very similar among the groups. Hydroxyproline concentration in G3 (36.3 µg/g) was lower by trend (p = 0.072) than in G1 (51.7 µg/g) and G2 (46.4 µg/g). The histological evaluation showed similar results regarding necrosis, inflammatory cells, edema, and epithelization for all groups. G3 (2.56) showed a distinctly worse score for submucosal bridging (p = 0.061) than G1 (1.68). A highly significant increase (p = 0.008) in CRP was detected in G3 (598.96 ng/ml) compared to G1 (439.49 ng/ml) and G2 (460 ng/ml). CONCLUSION: A combination of high temperature and humidity during surgery induces an increased systemic inflammatory response and seems to be attenuating the early regeneration process in the anastomotic tissue.


Asunto(s)
Fuga Anastomótica/prevención & control , Humedad , Intestinos/cirugía , Periodo Intraoperatorio , Temperatura , Cicatrización de Heridas/fisiología , Anastomosis Quirúrgica/métodos , Animales , Proteína C-Reactiva/metabolismo , Hidroxiprolina/metabolismo , Intestinos/patología , Intestinos/fisiopatología , Masculino , Ratas Wistar , Resistencia a la Tracción , Adherencias Tisulares/patología
17.
Surgery ; 154(3): 596-603, 2013 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-23876362

RESUMEN

BACKGROUND: It has been shown that crystalloid fluid-overload promotes anastomotic instability. As physiologic anastomotic healing requires the sequential infiltration of different cells, we hypothesized this to be altered by liberal fluid regimes and performed a histomorphological analysis. METHODS: 36 Wistar rats were randomized into 4 groups (n=8-10 rats/group) and treated with either liberal (+) or restrictive (-) perioperative crystalline (Jonosteril = Cry) or colloidal fluid (Voluven = Col). Anastomotic samples were obtained on postoperative day 4, routinely stained and histophathologically reviewed. Anastomotic healing was assessed using a semiquantitative score, assessing inflammatory cells, anastomotic repair and collagenase activity. RESULTS: Overall, the crystalloid overload group (Cry (+)) showed the worst healing score (P < 0.01). A substantial increase of lymphocytes and macrophages was found in this group compared to the other three (P < 0.01). Both groups that received colloidal fluid (Col (+) and Col (-)) as well as the group that received restricted crystalloid fluid resuscitation (Cry (-)) had better intestinal healing. Collagenase activity was significantly higher in the Cry (+) group. CONCLUSION: Intraoperative infusion of high-volume crystalloid fluid leads to a pathological anastomotic inflammatory response with a marked infiltration of leukocytes and macrophages resulting in accelerated collagenolysis.


Asunto(s)
Anastomosis Quirúrgica , Inflamación/patología , Intestinos/cirugía , Soluciones Isotónicas/administración & dosificación , Cicatrización de Heridas , Animales , Colágeno/análisis , Soluciones Cristaloides , Inmunohistoquímica , Intestinos/patología , Leucocitos/fisiología , Macrófagos/fisiología , Masculino , Metaloproteinasa 13 de la Matriz/análisis , Metaloproteinasa 2 de la Matriz/análisis , Ratas , Ratas Wistar
18.
Int J Colorectal Dis ; 28(8): 1135-41, 2013 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-23468250

RESUMEN

INTRODUCTION: Although advances in multimodal treatment have led to prolongation of survival in patients after resection of colorectal liver metastasis (CRC-LM), most patients develop recurrence, which is often confined to the liver. Repeat hepatic resection (RHR) may prolong survival or even provide cure in selected patients. We evaluated the perioperative and long-term outcomes after RHR for CRC-LM in a single institution series. PATIENTS AND METHODS: Since 1999, 92 repeat hepatic resections (63% wedge/segmental, 37% hemihepatectomy or greater) for recurrent CRC-LM were performed in 80 patients. Median interval from initial liver resection to first RHR was 1.25 years. Any kind of chemotherapy (CTx) had been given in 88% before RHR. Neoadjuvant CTx was given in 38%. RESULTS: Hepatic margin-negative resection was achieved in 79%. Mortality was 3.8%. Overall complication rates were 53%, including infection (17%), operative re-intervention (12%), and hepatic failure (5.4%). Overall 5-year survival after first RHR was 50.3%. Univariately, primary tumor stage, the extent of liver resection, postoperative complications, and the overall resection margin correlated with survival. By multivariate analysis, primary T stage, size of metastasis, and overall R0 resection influenced survival. Survival was not independently influenced by hepatic resection margins or (neoadjuvant) CTx. CONCLUSIONS: Repeat hepatic resection for recurrent CRC-LM can be performed with low mortality and acceptable morbidity. Survival after repeat hepatic resection in this selected group of patients is encouraging and comparable to results after first liver resections.


Asunto(s)
Neoplasias Colorrectales/patología , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/cirugía , Demografía , Femenino , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/mortalidad , Masculino , Análisis Multivariante , Reoperación , Análisis de Supervivencia , Resultado del Tratamiento
19.
World J Gastroenterol ; 17(10): 1308-16, 2011 Mar 14.
Artículo en Inglés | MEDLINE | ID: mdl-21455330

RESUMEN

AIM: To investigate the influence of remote ischemic preconditioning (RIPC) on anastomotic integrity. METHODS: Sixty male Wistar rats were randomized to six groups. The control group (n = 10) had an end-to-end ileal anastomosis without RIPC. The preconditioned groups (n = 34) varied in time of ischemia and time of reperfusion. One group received the amino acid L-arginine before constructing the anastomosis (n = 9). On postoperative day 4, the rats were re-laparotomized, and bursting pressure, hydroxyproline concentration, intra-abdominal adhesions, and a histological score concerning the mucosal ischemic injury were collected. The data are given as median (range). RESULTS: On postoperative day 4, median bursting pressure was 124 mmHg (60-146 mmHg) in the control group. The experimental groups did not show a statistically significant difference (P > 0.05). Regarding the hydroxyproline concentration, we did not find any significant variation in the experimental groups. We detected significantly less mucosal injury in the RIPC groups. Furthermore, we assessed more extensive intra-abdominal adhesions in the preconditioned groups than in the control group. CONCLUSION: RIPC directly before performing small bowel anastomosis does not affect anastomotic stability in the early period, as seen in ischemic preconditioning.


Asunto(s)
Anastomosis Quirúrgica , Intestino Delgado/patología , Precondicionamiento Isquémico/métodos , Cicatrización de Heridas , Animales , Arginina/metabolismo , Hidroxiprolina/biosíntesis , Hidroxiprolina/metabolismo , Laparotomía , Masculino , Membrana Mucosa/patología , Presión , Ratas , Ratas Wistar , Adherencias Tisulares
20.
Surg Endosc ; 25(7): 2323-9, 2011 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-21298527

RESUMEN

BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) is frequently performed as a definitive bariatric procedure today. Quantitative data on the detailed anatomy of the stomach after LSG are yet sparse. METHODS: Thirty-two multislice computed tomography (MSCT) data sets acquired in 27 LSG patients (22 female, 5 male) with a dedicated examination protocol and post-processing were evaluated for gastric volume, stomach length, sleeve length, antrum length, staple line length, and maximum cross-sectional sleeve area. Obtained parameters were compared to time after surgery, weight loss, and the occurrence of postsurgical regurgitation. RESULTS: Mean gastric volume was 186.5±88.4 ml. Gastric volume correlated significantly with the time interval after surgery. Sleeve sizes of 105.3±30.2 ml during early follow-up confirmed correct primary sizing of the sleeve, whereas marked dilation to 196.8±84.3 ml was found in patients with a follow-up of 6 months and longer (p=0.038). Sleeve area and staple line length were also positively correlated with time after surgery. No correlation was found between gastric volume and excess weight loss. In ten patients an intrathoracic migration of the staple line could be noted, with four of these patients developing persistent regurgitation after LSG. Regurgitation was present in only 2 of 17 patients without sleeve herniation. CONCLUSION: Multislice computed tomography allows for a comprehensive and quantitative evaluation of the anatomy after LSG and thus provides new insights in the process of sleeve dilation. Intrathoracic migration of the staple line could be identified as a possible cause of persistent regurgitation.


Asunto(s)
Gastrectomía/métodos , Imagenología Tridimensional , Laparoscopía/métodos , Obesidad Mórbida/cirugía , Estómago/diagnóstico por imagen , Tomografía Computarizada por Rayos X , Adulto , Anciano , Femenino , Reflujo Gastroesofágico/diagnóstico por imagen , Humanos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/diagnóstico por imagen , Interpretación de Imagen Radiográfica Asistida por Computador , Estudios Retrospectivos , Estómago/cirugía , Resultado del Tratamiento
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