Silvia Salvans

Postoperative peritoneal infection enhances migration and invasion capacities of tumor cells in vitro: an insight into the association between anastomotic leak and recurrence after surgery for colorectal cancer.

Objective:The aim of this study was to investigate the effect of postoperative peritoneal infection on proliferation, migration, and invasion capacities of cancer cells lines in vitro after surgery for colorectal cancer. Background:Anastomotic leakage is associated with higher rates of recurrence after surgery for colorectal cancer. However, the mechanisms responsible are unknown. We hypothesized that the infection-induced inflammatory response may enhance tumor progression features of residual cancer cells. Methods:Prospective matched cohort study. Patients undergoing surgery for colorectal cancer with curative intent (January 2008—March 2012) were included. Patients who had an anastomotic leak or intra-abdominal abscess were included in the infection group (n = 47). For each case patient, another patient with an uncomplicated postoperative course was selected for the control group (n = 47).In vitro treatments on cancer cell lines (MDA-MB-231 and SW620) were performed using baseline and postoperative serum and peritoneal fluid samples to determine cell proliferation and cell migration/invasion activities. Results:Postoperative peritoneal fluid from infected patients enhanced both cell migration (infection: 140 ± 85 vs control: 94 ± 30; P = 0.016) and cell invasion (infection: 117 ± 31 vs control: 103 ± 16; P = 0.024) capacities of cancer cell lines. With serum samples, these effects were only observed in cell migration assays (infection: 98 ± 28 vs control: 87 ± 17; P = 0.005). Some minor activation of cell proliferation was observed by treatment with serum from infection group. Two-year cumulative disease-free survival was significantly lower in patients with postoperative peritoneal infection (infection: 77.6% vs control: 90.6%; P = 0.032). Conclusions:Our results suggest that postoperative peritoneal infection enhances the invasive capacity of residual tumor cells after surgery, thus facilitating their growth to recurrent tumors.

Preoperative administration of erythropoietin stimulates tumor recurrence after surgical excision of colon cancer in mice by a vascular endothelial growth factor-independent mechanism.

BACKGROUND It has been suggested that preoperative administration of erythropoietin (Epo) in patients with gastrointestinal cancer reduces transfusional needs and is also associated with lower morbidity. On the other hand, experimental and clinical studies show that Epo might enhance tumor growth and angiogenesis. Our aim was to ascertain whether preoperative administration of Epo has any effect on tumor recurrence after curative surgery using an experimental model of colon cancer. MATERIALS AND METHODS We induced tumors by injecting B51LiM colon cancer cells into the cecal wall of Balb/c mice. We randomized the animals into three groups of treatment with (1) recombinant human Epo, (2) recombinant mouse Epo, or (3) vehicle alone, for 12 d until cecectomy. On postoperative day 12, we killed mice and analyzed tumor recurrence. We measured serum levels of vascular endothelial growth factor and determined vascular endothelial growth factor expression and tumor microvessel density by immunohistochemistry. We also investigated the in vitro effect of Epo on B51LiM cell line proliferation. RESULTS All three groups displayed tumor recurrence, but the final tumor load score and total tumoral weight were higher in the two groups that included Epo. The differences were statistically significant when we compared the recombinant mouse Epo group with the control group. We found no evidence of increased angiogenesis or enhanced cell proliferation as possible mechanisms of Epo-induced recurrence. CONCLUSIONS Preoperative administration of Epo stimulates tumor recurrence in an animal model of colon cancer. Our results point to the need for further research on the mechanisms of tumor growth enhancement by Epo, to better understand the benefits or disadvantages of Epo treatment.

Rehabilitación multimodal en cirugía electiva colorrectal: evaluación de la curva de aprendizaje con 300 pacientes

INTRODUCTION The aim of this paper is to assess the learning curve on compliance to the application of a multimodal rehabilitation program (MMRP) protocol and patient recovery after elective colorectal surgery. MATERIAL AND METHODS A comparative prospective study of 3 consecutive cohorts of 100 patients (P1, P2 and P3) who had colonic or rectal surgery. The same MMRP protocol was applied in all cases. Compliance to the protocol, tolerance to the diet and walking have been analysed. The percentages of early hospital discharges have also been compared. RESULTS Compliance gradually improved, reaching statistical significance between P1 and P3. Starting the diet on day 1 post-surgery was 52% vs 86% (p=0.0001) and the removal of drips was 21% vs 40% (p=0.005). This difference remained during days 2 and 3. Tolerance to the diet on day 1 (P1: 34% vs. P3: 66%; p=0.0001) and walking on day 2 (P1: 41% vs. P3: 68%; p=0.0002) were also better in the third period. No differences in morbidity were found between the three periods. The percentage of hospital discharges on day 3 P1: 1% vs. P3: 15%; p=0.0003), day 4 (P1: 12% vs. P3: 32%; p=0.001) and day 5 (P1: 30% vs. P3: 50%; p=0.002) was higher in the third period. CONCLUSIONS The compliance to the protocol and the results of applying the MMRP improved significantly with the greater experience of the professionals involved.

Descripción de los hallazgos de la ecografía endoanal en pacientes con incontinencia fecal mediante un sistema de puntuación

INTRODUCTION The main aim of the study was to apply a severity classification of sphincter lesions detected by endoanal ultrasound using Starck score in patients who suffered faecal incontinence. MATERIAL AND METHOD Data were analysed on 133 patients with faecal incontinence. Those in whom anal sphincter lesions were detected by endoanal ultrasound are described and their corresponding scores according to Starck classification calculated. This system scores severity of detected sphincter lesions from 0 to 16, involving the three axes of the anal canal. Patient demographic characteristics and anorectal manometry results were also analysed. The relationship between this score, patient gender and age, and anorectal manometric results were also analysed. RESULTS A total of 83 (62.4%) patients had some type of anal sphincter lesion. The presence of sphincter defects was not related to gender (P=0.172), although it did correlate with younger ages (P=0.028). The severity of anal sphincter damage by Starck score did not show significant correlation to gender (P=0.327) or to the age (P=0.350) of patients. However, a significant correlation was detected between Starck score and anal resting pressure (P=0.008) or anorectal squeeze pressure (P=0.011). CONCLUSIONS The presence of anal sphincter injuries could be well defined by Starck score in patients with faecal incontinence. Severity of damage scored by Starck correlated with anorectal manometric results.

Tratamiento ambulatorio de la diverticulitis aguda no complicada: impacto sobre los costes sanitarios

BACKGROUND Outpatient treatment of uncomplicated acute diverticulitis is safe and effective. The aim of this study was to determine the impact of outpatient treatment on the reduction of healthcare costs. PATIENTS AND METHODS A retrospective cohort study comparing 2 groups was performed. In the outpatient treatment group, patients diagnosed with uncomplicated acute diverticulitis were treated with oral antibiotics at home. In the hospital treatment group, patients met the criteria for outpatient treatment but were admitted to hospital and received intravenous antibiotic therapy. Cost estimates have been made using the hospital cost accounting system based on total costs, the sum of all variable costs (direct costs) plus overhead expenses divided by activity (indirect costs). RESULTS A total of 136 patients were included, 90 in the outpatient treatment group and 46 in the hospital group. There were no differences in the characteristics of the patients in both groups. There were also no differences in the treatment failure rate in both groups (5.5% vs. 4.3%; P=.7). The total cost per episode was significantly lower in the outpatient treatment group (882 ± 462 vs. 2.376 ± 830 euros; P=.0001). CONCLUSIONS Outpatient treatment of acute diverticulitis is not only safe and effective but also reduces healthcare costs by more than 60%.

Tratamiento del dolor anal por patología anorrectal aguda en urgencias: ¿baños de asiento con agua fría o caliente? resultados de un ensayo clínico aleatorizado

INTRODUCTION The popular belief advocates the use of sitz (sitting) baths with cold water for the treatment of acute anal pain, but clinical practice guides recommend the use of hot water for its known effect on the at-rest anal pressure. AIM The objective of the study was to examine the analgesic effect on the quality of life, manometer data and clinical progress, of the two temperatures in sitz baths in patients with anal pain. MATERIAL AND METHODS A randomised clinical trial on patients with acute anal pain due to haemorrhoids or anal fissures, divided into Group 1: Sitz baths with water at a temperature of less than 15 degrees C, and Group 2: Baths with a water temperature above 30 degrees C. The analgesia was the same in both groups. An analysis was made of the pain at 7 days (visual analogue scale), quality of life (SF-36), anal at-rest pressure and disease progress. RESULTS Of the 27 eligible patients, 24 were randomised (Group 1: n=12 y Group 2: n=12). There were no statistical differences in pain, but it remained stable in Group 1, but gradually decreased in the patients of Group 2, the difference being in the pain scores on the first day compared to the seventh in Group 2 (p=0.244). The rest of the variables were similar. CONCLUSION There were no statistically significant differences in pain control from day 1 to day 7 in the Group with sitz baths with hot water. (ISRCTN Number: 50105150).

[Cold or hot sitz baths in the emergency treatment of acute anal pain due to anorectal disease? Results of a randomised clinical trial].

Abstract Introduction The popular belief advocates the use of sitz (sitting) baths with cold water for the treatment of acute anal pain, but clinical practice guides recommend the use of hot water for its known effect on the at-rest anal pressure. Aim The objective of the study was to examine the analgesic effect on the quality of life, manometer data and clinical progress, of the two temperatures in sitz baths in patients with anal pain. Material and methods A randomised clinical trial on patients with acute anal pain due to haemorrhoids or anal fissures, divided into Group 1: Sitz baths with water at a temperature of less than 15°C, and Group 2: Baths with a water temperature above 30°C. The analgesia was the same in both groups. An analysis was made of the pain at 7 days (visual analogue scale), quality of life (SF-36), anal at-rest pressure and disease progress. Results Of the 27 eligible patients, 24 were randomised (Group 1: n=12 y Group 2: n=12). There were no statistical differences in pain, but it remained stable in Group 1, but gradually decreased in the patients of Group 2, the difference being in the pain scores on the first day compared to the seventh in Group 2 (P=.244). The rest of the variables were similar. Conclusion There were no statistically significant differences in pain control from day 1 to day 7 in the Group with sitz baths with hot water.

Multimodal (fast-track) rehabilitation in elective colorectal surgery: Evaluation of the learning curve with 300 patients

Abstract Introduction The aim of this paper is to assess the learning curve on compliance to the application of a multimodal rehabilitation program (MMRP) protocol and patient recovery after elective colorectal surgery. Material and methods A comparative prospective study of 3 consecutive cohorts of 100 patients (P1, P2 and P3) who had colonic or rectal surgery. The same MMRP protocol was applied in all cases. Compliance to the protocol, tolerance to the diet and walking have been analysed. The percentages of early hospital discharges have also been compared. Results Compliance gradually improved, reaching statistical significance between P1 and P3. Starting the diet on day 1 post-surgery was 52% vs 86% (P=.0001) and the removal of drips was 21% vs 40% (P=.005). This difference remained during days 2 and 3. Tolerance to the diet on day 1 (P1: 34% vs P3: 66%; P=.0001) and walking on day 2 (P1: 41% vs P3: 68%; P=.0002) were also better in the third period. No differences in morbidity were found between the three periods. The percentage of hospital discharges on day 3 P1: 1% vs P3: 15%; P=.0003), day 4 (P1: 12% vs P3: 32%; P=.001) and day 5 (P1: 30% vs P3: 50%; P=.002) was higher in the third period. Conclusions The compliance to the protocol and the results of applying the MMRP improved significantly with the greater experience of the professionals involved.

Modulation of the colon cancer cell phenotype by pro-inflammatory macrophages: A preclinical model of surgery-associated inflammation and tumor recurrence

Peritoneal infection after colorectal cancer surgery is associated with a higher rate of tumor relapse. We have recently proposed that soluble inflammatory factors released in response to a postoperative infection enhance tumor progression features in residual tumor cells. In an effort to set up models to study the mechanisms of residual tumor cell activation during surgery-associated inflammation, we have analyzed the phenotypic response of colon cancer cell lines to the paracrine effects of THP-1 and U937 differentiated human macrophages, which release an inflammatory medium characteristic of an innate immune response. The exposure of the colon cancer cell lines HT-29 and SW620 to conditioned media isolated from differentiated THP-1 and U937 macrophages induced a mesenchymal-like phenotypic shift, involving the activation of in vitro invasiveness. The inflammatory media activated the β-catenin/TCF4 transcriptional pathway and induced the expression of several mesenchymal (e.g., FN1 and VIM) and TCF4 target genes (e.g., MMP7, PTGS2, MET, and CCD1). Similarly, differential expression of some transcription factors involved in epithelial-to-mesenchymal transitions (i.e. ZEB1, SNAI1, and SNAI2) was variably observed in the colon cancer cell lines when exposed to the inflammatory media. THP-1 and U937 macrophages, which displayed characteristics of M1 differentiation, overexpressed some cytokines previously shown to be induced in colorectal cancer patients with increased rates of tumor recurrence associated with postoperative peritoneal infections, thus suggesting their pro-tumoral character. Therefore, the environment created by inflammatory M1 macrophages enhances features of epithelial-to-mesenchymal transition, and may be useful as a model to characterize pro-inflammatory cytokines as putative biomarkers of tumor recurrence risk.

Hernias de la incisión de asistencia tras resección colorrectal laparoscópica. Influencia de la localización de la incisión y del uso de una malla profiláctica

OBJECTIVES To determine the incidence of incisional hernia (IH) in the extraction incision (EI) in colorectal resection for cancer. To analyze whether the location of the incision has any relationship with the incidence of hernias and whether mesh could be useful for prevention in high-risk patients. METHODS Retrospective review of the colon and rectal surgery database from January 2015 to December 2016. Data were classified into 2groups, transverse (TI) and midline incision (MI), and the latter was divided into 2subgroups (mesh [MIM] and suture [MIS]). Patients were classified using the HERNIAscore. Hernias were diagnosed by clinical and/or CT examination. RESULTS A total of 182 out of 210 surgical patients were included. After a median follow-up of 13.0 months, 39 IH (21.9%) were detected, 23 of which (13.4%) were in the EI; their frequency was lower in the TI group (3.4%) and in the MIM group (5.9%) than in the MIS group (29.5%; p=0.007). The probability of developing IH in the MIS group showed an OR=11.7 (95%CI: 3.3-42.0) compared to the TI group and 4.3 (IC 95%: 1.1-16.3) versus the MIM group. CONCLUSIONS The location of the incision is relevant to avoid incisional hernias. Transverse incisions should be used as the first option. When a midline incision is needed, a prophylactic mesh could be considered in high risk patients because it is safe and associated with low morbidity.