Management of acute diverticulitis with pericolic free gas (ADIFAS). an international multicenter observational study

Background: There are no specific recommendations regarding the optimal management of this group of patients. The World Society of Emergency Surgery suggested a nonoperative strategy with antibiotic therapy, but this was a weak recommendation. This study aims to identify the optimal management of patients with acute diverticulitis (AD) presenting with pericolic free air with or without pericolic fluid. Methods: A multicenter, prospective, international study of patients diagnosed with AD and pericolic-free air with or without pericolic free fluid at a computed tomography (CT) scan between May 2020 and June 2021 was included. Patients were excluded if they had intra-abdominal distant free air, an abscess, generalized peritonitis, or less than a 1-year follow-up. The primary outcome was the rate of failure of nonoperative management within the index admission. Secondary outcomes included the rate of failure of nonoperative management within the first year and risk factors for failure. Results: A total of 810 patients were recruited across 69 European and South American centers; 744 patients (92%) were treated nonoperatively, and 66 (8%) underwent immediate surgery. Baseline characteristics were similar between groups. Hinchey II-IV on diagnostic imaging was the only independent risk factor for surgical intervention during index admission (odds ratios: 12.5, 95% CI: 2.4-64, P =0.003). Among patients treated nonoperatively, at index admission, 697 (94%) patients were discharged without any complications, 35 (4.7%) required emergency surgery, and 12 (1.6%) percutaneous drainage. Free pericolic fluid on CT scan was associated with a higher risk of failure of nonoperative management (odds ratios: 4.9, 95% CI: 1.2-19.9, P =0.023), with 88% of success compared to 96% without free fluid ( P <0.001). The rate of treatment failure with nonoperative management during the first year of follow-up was 16.5%. Conclusion: Patients with AD presenting with pericolic free gas can be successfully managed nonoperatively in the vast majority of cases. Patients with both free pericolic gas and free pericolic fluid on a CT scan are at a higher risk of failing nonoperative management and require closer observation

Infección peritoneal postoperatoria y recurrencia del cáncer colorrectal: estudio de la capacidad de proliferación, migración e invasión de células tumorales in vitro como mecanismos responsables de esta asociación

La dehiscencia de anastomosis después de cirugía de cáncer colorrectal (CCR) se asocia a una mayor recurrencia tumoral. Sin embargo, los mecanismos responsables de esta asociación son aún desconocidos. En un trabajo previo demostramos que la respuesta inflamatoria y angiogénica secundaria a la infección peritoneal tras cirugía de CCR es mayor que en los pacientes que no presentan ninguna complicación postoperatoria. Esta respuesta amplificada podría tener un efecto negativo en los pacientes con CCR. Otro de los mecanismos que podría explicar esta asociación sería la adquisición de un fenotipo invasivo de células tumorales residuales en presencia de infección. El primer objetivo de este proyecto de investigación fue confirmar nuestros resultados previos y ampliar el estudio a otras citoquinas inflamatorias y angiogénicas. En segundo lugar, investigamos el efecto de la infección peritoneal tras cirugía de CCR sobre la proliferación, migración e invasión de líneas celulares de cáncer in vitro. Se realizó un estudio prospectivo de cohortes con controles apareados en pacientes intervenidos de CCR con intención curativa. Los pacientes que presentaron un absceso intraabdominal o una dehiscencia anastomótica fueron incluidos en el grupo infección. También se seleccionó otro paciente sin ninguna complicación postoperatoria para el grupo control. Las variables de apareamiento fueron sexo, edad, localización tumoral, abordaje quirúrgico, estadio tumoral y tratamiento neoadyuvante en los pacientes con cáncer de recto. Se obtuvieron muestras de sangre y líquido peritoneal antes de la cirugía y al cuarto día postoperatorio o en el momento del diagnóstico de la infección. Se analizaron 43 citoquinas inflamatorias y angiogénicas en las muestras de suero postoperatorias mediante arrays de anticuerpos. Los ensayos in vitro consistieron en el cultivo de células tumorales MDA-MB-231 y SW620 que se trataron con muestras de suero y líquido peritoneal preoperatorias y postoperatorias. Los ensayos de proliferación, migración e invasión realizados se basaron en el método colorimétrico en el cual se utiliza la actividad de la enzima hexosaminidasa como cuantificación del número de células viables. Durante el periodo de estudio, 47 pacientes fueron incluidos en el grupo infección con sus correspondientes controles. Todas las citoquinas analizadas fueron significativamente mayores en el grupo infección. Las muestras de suero postoperatorias de pacientes del grupo infección mostraron un aumento significativo de la proliferación de células MDA-MB-231. Este efecto fue más evidente cuando comparamos la diferencia de proliferación entre muestras postoperatorias y preoperatorias, entre grupos. Además, observamos una mayor inducción de la migración celular en el grupo infección al aplicar muestras de suero postoperatorio aunque no encontramos diferencias de actividad celular invasiva entre grupos. No hallamos diferencias de proliferación celular entre grupos al tratar las células con muestras de líquido peritoneal postoperatorias. Sin embargo, algunas de estas muestras mostraron un efecto citotóxico no relacionado con la presencia de infección. Las muestras postoperatorias de líquido peritoneal del grupo infección mostraron un incremento significativo de la migración de células MDA-MB-231 y de la invasión de células SW620. Este efecto también se observó al comparar las diferencias entre muestras postoperatorias y preoperatorias entre ambos grupos. La supervivencia libre de enfermedad fue significativamente menor en el grupo infección. La infección peritoneal postoperatoria se asoció a recurrencia tumoral. El riesgo de padecer una recurrencia tumoral fue casi tres veces mayor si se sufrió una infección peritoneal postoperatoria en nuestra muestra de pacientes. En conclusión, la expresión de citoquinas inflamatorias y angiogénicas después de cirugía de CCR es mayor en presencia de infección peritoneal. La infección peritoneal postoperatoria estimula la proliferación, migración e invasión de las células tumorales in vitro. Estos mecanismos podrían ser responsables, al menos en parte, de la asociación entre la infección peritoneal y la recurrencia tumoral tras la cirugía del CCR.Anastomotic leakage after colorectal cancer (CRC) surgery is associated with higher tumor recurrence. However, the mechanisms responsible for this association are unknown. In a previous study we showed that inflammatory and angiogenic responses after CRC surgery were higher in patients with postoperative infection than in patients with no postoperative complication. A magnification of these responses could enhance a negative effect in patients with cancer. Another mechanism that would explain this association might be the acquirement of an invasive phenotype of residual tumor cells in the presence of peritoneal infection. The aim of this study was to confirm our previous results and extend the study to other inflammatory and angiogenic cytokines; and investigate the effect of postoperative peritoneal infection after CRC surgery on proliferation, migration, and invasion capacities of tumor cells in vitro. We performed a prospective cohort study with matched controls of patients who underwent elective surgery for CRC with curative intent. Patients who had an intra-abdominal abscess or an anastomotic leak were included in the infection group. For each patient with infection another patient with an uncomplicated postoperative course was selected for the control group. Controls were matched for gender, age, tumor location, surgical approach, tumor stage and neoadjuvant therapy in patients with rectal cancer. Blood and peritoneal fluid samples were collected before surgery and on postoperative day 4 or at the moment a peritoneal infection was diagnosed. We analyzed 43 different inflammatory and/or angiogenic cytokines in the sera of these patients with antibody arrays. In vitro assays on cancer cell lines (MDA-MB-231 and SW620) were performed using preoperative and postoperative serum and peritoneal fluid samples. The assays were performed according to the colorimetric method based on the activity of the lysosomal hexosaminidase enzyme as a measure of the number of viable cells. During the study period, 47 patients were included in the infection group: 34 patients developed an anastomotic leak and 13 patients an intraabdominal abscess. All cytokines tested were significantly induced in the infection group. Postoperative serum samples from patients with peritoneal infection significantly increased proliferation in the MDA-MB-231 cell line compared with controls. This effect was most apparent when comparing the increase in cell proliferation exerted by postoperatory samples respect to preoperatory samples within each group. We also observed a major induction of migration activity with the infection group postoperative serum samples. Cell invasion assays with serum samples did not reveal significant differences between groups. We found no differences in cell proliferation between both groups when cells were treated with peritoneal fluid samples. However, some postoperative peritoneal fluid samples exerted a cytotoxic effect on cell cultures that was not related to the presence of infection. Postoperative peritoneal fluids taken from the infection group rendered a significant increase in the capacity of MDA-MB-231 migration and SW620 invasion capacities. This effect was also apparent when comparing the difference activity between postoperative and preoperative samples in both groups. During follow-up, 12 patients developed tumor recurrence in the infection group and 6 in the control group. Cumulative disease-free survival was significantly lower in patients with postoperative peritoneal infection. The risk of tumor recurrence was almost three times higher if patients suffered a postoperative peritoneal infection in our sample. In conclusion, our results confirm that postoperative peritoneal infection induces a large number of serum cytokines. Furthermore, postoperative peritoneal infection enhances proliferation, migration and invasion capacities of tumor cells in vitro. These mechanisms might be responsible, at least in part, for the association between peritoneal infection and tumor recurrence after CRC surgery

Laparoscopic colorectal surgery: current status and implementation of the latest technological innovations.

The introduction of laparoscopy is an example of surgical innovation with a rapid implementation in many areas of surgery. A large number of controlled studies and meta-analyses have shown that laparoscopic colorectal surgery is associated with the same benefits than other minimally invasive procedures, including lesser pain, earlier recovery of bowel transit and shorter hospital stay. On the other hand, despite initial concerns about oncological safety, well-designed prospective randomized multicentre trials have demonstrated that oncological outcomes of laparoscopy and open surgery are similar. Although the use of laparoscopy in colorectal surgery has increased in recent years, the percentages of patients treated with surgery using minimally invasive techniques are still reduced and there are also substantial differences among centres. It has been argued that the limiting factor for the use of laparoscopic procedures is the number of surgeons with adequate skills to perform a laparoscopic colectomy rather than the tumour of patients' characteristics. In this regard, future efforts to increase the use of laparoscopic techniques in colorectal surgery will necessarily require more efforts in teaching surgeons. We here present a review of recent controversies of the use of laparoscopy in colorectal surgery, such as in rectal cancer operations, the possibility of reproducing complete mesocolon excision, and the benefits of intra-corporeal anastomosis after right hemicolectomy. We also describe the results of latest innovations such as single incision laparoscopic surgery, robotic surgery and natural orifice transluminal endoscopic surgery for colon and rectal diseases

Infección peritoneal postoperatoria y recurrencia del cáncer colorrectal: estudio de la capacidad de proliferación, migración e invasión de células tumorales in vitro como mecanismos responsables de esta asociación

La dehiscencia de anastomosis después de cirugía de cáncer colorrectal (CCR) se asocia a una mayor recurrencia tumoral. Sin embargo, los mecanismos responsables de esta asociación son aún desconocidos. En un trabajo previo demostramos que la respuesta inflamatoria y angiogénica secundaria a la infección peritoneal tras cirugía de CCR es mayor que en los pacientes que no presentan ninguna complicación postoperatoria. Esta respuesta amplificada podría tener un efecto negativo en los pacientes con CCR. Otro de los mecanismos que podría explicar esta asociación sería la adquisición de un fenotipo invasivo de células tumorales residuales en presencia de infección. El primer objetivo de este proyecto de investigación fue confirmar nuestros resultados previos y ampliar el estudio a otras citoquinas inflamatorias y angiogénicas. En segundo lugar, investigamos el efecto de la infección peritoneal tras cirugía de CCR sobre la proliferación, migración e invasión de líneas celulares de cáncer in vitro. Se realizó un estudio prospectivo de cohortes con controles apareados en pacientes intervenidos de CCR con intención curativa. Los pacientes que presentaron un absceso intraabdominal o una dehiscencia anastomótica fueron incluidos en el grupo infección. También se seleccionó otro paciente sin ninguna complicación postoperatoria para el grupo control. Las variables de apareamiento fueron sexo, edad, localización tumoral, abordaje quirúrgico, estadio tumoral y tratamiento neoadyuvante en los pacientes con cáncer de recto. Se obtuvieron muestras de sangre y líquido peritoneal antes de la cirugía y al cuarto día postoperatorio o en el momento del diagnóstico de la infección. Se analizaron 43 citoquinas inflamatorias y angiogénicas en las muestras de suero postoperatorias mediante arrays de anticuerpos. Los ensayos in vitro consistieron en el cultivo de células tumorales MDA-MB-231 y SW620 que se trataron con muestras de suero y líquido peritoneal preoperatorias y postoperatorias. Los ensayos de proliferación, migración e invasión realizados se basaron en el método colorimétrico en el cual se utiliza la actividad de la enzima hexosaminidasa como cuantificación del número de células viables. Durante el periodo de estudio, 47 pacientes fueron incluidos en el grupo infección con sus correspondientes controles. Todas las citoquinas analizadas fueron significativamente mayores en el grupo infección. Las muestras de suero postoperatorias de pacientes del grupo infección mostraron un aumento significativo de la proliferación de células MDA-MB-231. Este efecto fue más evidente cuando comparamos la diferencia de proliferación entre muestras postoperatorias y preoperatorias, entre grupos. Además, observamos una mayor inducción de la migración celular en el grupo infección al aplicar muestras de suero postoperatorio aunque no encontramos diferencias de actividad celular invasiva entre grupos. No hallamos diferencias de proliferación celular entre grupos al tratar las células con muestras de líquido peritoneal postoperatorias. Sin embargo, algunas de estas muestras mostraron un efecto citotóxico no relacionado con la presencia de infección. Las muestras postoperatorias de líquido peritoneal del grupo infección mostraron un incremento significativo de la migración de células MDA-MB-231 y de la invasión de células SW620. Este efecto también se observó al comparar las diferencias entre muestras postoperatorias y preoperatorias entre ambos grupos. La supervivencia libre de enfermedad fue significativamente menor en el grupo infección. La infección peritoneal postoperatoria se asoció a recurrencia tumoral. El riesgo de padecer una recurrencia tumoral fue casi tres veces mayor si se sufrió una infección peritoneal postoperatoria en nuestra muestra de pacientes. En conclusión, la expresión de citoquinas inflamatorias y angiogénicas después de cirugía de CCR es mayor en presencia de infección peritoneal. La infección peritoneal postoperatoria estimula la proliferación, migración e invasión de las células tumorales in vitro. Estos mecanismos podrían ser responsables, al menos en parte, de la asociación entre la infección peritoneal y la recurrencia tumoral tras la cirugía del CCR.Anastomotic leakage after colorectal cancer (CRC) surgery is associated with higher tumor recurrence. However, the mechanisms responsible for this association are unknown. In a previous study we showed that inflammatory and angiogenic responses after CRC surgery were higher in patients with postoperative infection than in patients with no postoperative complication. A magnification of these responses could enhance a negative effect in patients with cancer. Another mechanism that would explain this association might be the acquirement of an invasive phenotype of residual tumor cells in the presence of peritoneal infection. The aim of this study was to confirm our previous results and extend the study to other inflammatory and angiogenic cytokines; and investigate the effect of postoperative peritoneal infection after CRC surgery on proliferation, migration, and invasion capacities of tumor cells in vitro. We performed a prospective cohort study with matched controls of patients who underwent elective surgery for CRC with curative intent. Patients who had an intra-abdominal abscess or an anastomotic leak were included in the infection group. For each patient with infection another patient with an uncomplicated postoperative course was selected for the control group. Controls were matched for gender, age, tumor location, surgical approach, tumor stage and neoadjuvant therapy in patients with rectal cancer. Blood and peritoneal fluid samples were collected before surgery and on postoperative day 4 or at the moment a peritoneal infection was diagnosed. We analyzed 43 different inflammatory and/or angiogenic cytokines in the sera of these patients with antibody arrays. In vitro assays on cancer cell lines (MDA-MB-231 and SW620) were performed using preoperative and postoperative serum and peritoneal fluid samples. The assays were performed according to the colorimetric method based on the activity of the lysosomal hexosaminidase enzyme as a measure of the number of viable cells. During the study period, 47 patients were included in the infection group: 34 patients developed an anastomotic leak and 13 patients an intraabdominal abscess. All cytokines tested were significantly induced in the infection group. Postoperative serum samples from patients with peritoneal infection significantly increased proliferation in the MDA-MB-231 cell line compared with controls. This effect was most apparent when comparing the increase in cell proliferation exerted by postoperatory samples respect to preoperatory samples within each group. We also observed a major induction of migration activity with the infection group postoperative serum samples. Cell invasion assays with serum samples did not reveal significant differences between groups. We found no differences in cell proliferation between both groups when cells were treated with peritoneal fluid samples. However, some postoperative peritoneal fluid samples exerted a cytotoxic effect on cell cultures that was not related to the presence of infection. Postoperative peritoneal fluids taken from the infection group rendered a significant increase in the capacity of MDA-MB-231 migration and SW620 invasion capacities. This effect was also apparent when comparing the difference activity between postoperative and preoperative samples in both groups. During follow-up, 12 patients developed tumor recurrence in the infection group and 6 in the control group. Cumulative disease-free survival was significantly lower in patients with postoperative peritoneal infection. The risk of tumor recurrence was almost three times higher if patients suffered a postoperative peritoneal infection in our sample. In conclusion, our results confirm that postoperative peritoneal infection induces a large number of serum cytokines. Furthermore, postoperative peritoneal infection enhances proliferation, migration and invasion capacities of tumor cells in vitro. These mechanisms might be responsible, at least in part, for the association between peritoneal infection and tumor recurrence after CRC surgery

State of the art of enhanced recovery after surgery (ERAS) protocols in esophagogastric cancer surgery: the Western experience

Data de publicació electrònica: 21-06-2022Enhanced recovery after surgery (ERAS) programs provide a framework to standardize care processes and improve outcomes. The results of this multimodal and multidisciplinary approach based on actions focused on reducing physiological surgical stress in the preoperative, intraoperative, and postoperative periods are beneficial in reducing morbidity and hospital stay, without increasing readmissions across different surgical settings. The implementation of ERAS in resection procedures of esophageal and gastric cancer has been challenging due to the complexity of these surgical techniques and the high risk of complications. Despite the limited evidence of ERAS in esophagectomy operations, systematic reviews and meta-analysis have confirmed a reduction of pulmonary complications and hospital stay without increasing readmissions. In gastrectomy operations, the implementation of ERAS reduces the use of nasogastric tubes and intraabdominal drains, facilitates early diet, and reduces the length of hospital stay, without increasing complications. There is, however, wide heterogeneity and absence of standardization in the number and definition of the ERAS components. The development of ERAS consensus guidelines including procedure-specific components may reduce this variability. Regardless growing evidence of the effectiveness of ERAS, the adherence rate is still low. The commitment of the multidisciplinary team and leadership is critical in the application and refinement of ERAS protocols in parallel with periodic audits. Pre- and post-habilitation methods are emerging concepts to be incorporated in ERAS protocols

Accumulation of paneth cells in early colorectal adenomas is associated with beta-catenin signaling and poor patient prognosis

Background: previous studies in mice indicated that Paneth cells and c-Kit-positive goblet cells represent the stem cell niche of the small intestine and colon, respectively, partly by supporting Wnt and Notch activation. Whether these cell populations play a similar role in human intestinal cancer remains unexplored. Methods: we performed histopathological evaluation and immunohistochemical analysis of early colorectal adenomas and carcinoma adenoma from patients at the Hospital del Mar in Barcelona. We then determined the possible correlation between the different parameters analyzed and with patient outcomes. Results: paneth cells accumulate in a subset of human colorectal adenomas directly associated with Notch and Wnt/β-catenin activation. Adenoma areas containing Paneth cells display increased vessel density in the lamina propria and higher levels of the stem cell marker EphB2. In an in-house cohort of 200 colorectal adenoma samples, we also observed a significant correlation between the presence of Paneth cells and Wnt activation. Kaplan-Meier analysis indicated that early adenoma patients carrying Paneth cell-positive tumors display reduced disease-free survival compared with patients with Paneth cell-free lesions. Conclusions: our results indicate that Paneth cells contribute to the initial steps of cancer progression by providing the stem cell niche to adenoma cells, which could be therapeutically exploited

Loss of epithelial morphology.

<p>The inflammatory medium conditioned by macrophages induced a morphological shift in the epithelial colon cancer cell lines HT-29 and SW620 that was reminiscent of an epithelial-to-mesenchymal transition. Phase contrast microscopy images were obtained after treatment of colon cancer cell cultures for 2 days with the indicated conditioned media. <i>CON</i>, standard medium; <i>MONO-CM</i>, conditioned medium from non-activated monocytes; <i>MACRO-CM</i>, conditioned medium from differentiated macrophages.</p

Cell line-dependent cell proliferation and toxicity.

<p>The inflammatory medium conditioned by macrophages provoked a slowdown of cell proliferation in the HT-29 and SW620 cell lines, whereas it induced cell death in Caco2 cells. <b><i>A</i></b>, cell proliferation assays on HT-29 and SW620 during continuous treatment with the indicated conditioned media. Cell cultures were seeded at 3x10⁴/cm² and 2x10⁴/cm², respectively, and viable cells were calculated by trypan blue exclussion during the course of continuous treatment. The graph shows a representative experiment made in duplicates. <b><i>B</i></b>, cell countings were performed on the sixth day of the experiment shown in <i>A</i> and are expressed as the mean ± SD from 4 independent experiments (<i>*</i>, p = 0.068 with respect to <i>CON</i> or <i>MONO-CM</i> according to the Wilcoxon sign-rank test). <b><i>C</i></b>, cell viability was analyzed by clonogenicity assays as described in Materials and Methods, revealing that HT-29 cells preserved almost full viability after treatment with MACRO-CM for 48 hours while Caco2 cells underwent massive cell death. Results are shown as the percentage of visible colonies respect to 100% viability in cultures that had been treated with standard medium (<i>CON</i>). Percentage values are the mean ± SD from 6 independent experiments (<i>*</i>, p<0.050 with respect to <i>CON</i> or <i>MONO-CM</i> according to the Wilcoxon sign-rank test). <i>CON</i>, standard medium; <i>MONO-CM</i>, conditioned medium from non-activated monocytes; <i>MACRO-CM</i>, conditioned medium from differentiated macrophages.</p

PMA-differentiated THP-1 and U937 macrophages displayed features of a M1 type phenotype.

<p>PMA-differentiated THP-1 and U937 macrophages (<i>MACRO</i>) were harvested in parallel with non-treated cultures (<i>MONO</i>), and total RNA isolated. Some cultures were further incubated in the presence of medroxyprogesterone (<i>MPA</i>) for 24 hours or left untreated (<i>MPA-CON</i>), and similarly harvested and total RNA isolated. RNA samples were reverse transcribed to cDNA, and Real Time PCR analysis was performed using oligonucleotide primers specific for the indicated genes (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0192958#sec002" target="_blank">Material and Methods</a>). Markers of the M1 phenotype (<i>IL6</i>, <i>IL1B</i>, <i>CXCL10</i>) displayed strong induction during PMA-differentiation but were abruptly suppressed with further incubation with the M2 inducer MPA. In contrast, induction of the M2 markers CD163 and IL10 was modest, and in the case of CD163 potently enhanced by the M2 inducer MPA. Results are shown as the relative levels of each mRNA in the differentiated cell lines (<i>MACRO</i>, <i>MPA-CON</i>, <i>MPA</i>) respect to the non-treated monocytic cell lines (<i>MONO</i>) and expressed as the mean ± error of at least 2 independent experiments.</p