Revistas
Revista:
CANCERS
ISSN:
2072-6694
Año:
2023
Vol.:
15
N°:
4
Págs.:
1038
Simple Summary Netrin-1 (NTN-1) regulates obesity-associated low-grade inflammation, being also involved in the control of cell migration and proliferation. We aim to study whether excess visceral adipose tissue in patients with obesity and colon cancer is associated with increased NTN1 and the expression levels of its main receptors, promoting an inflammatory microenvironment that favours colon cancer development. Increased expression levels of NTN1 and its receptor NEO1 in the visceral adipose tissue from patients with obesity and colon cancer together with elevated DCC and UNC5B mRNA levels in patients with colon cancer were found. Moreover, the treatment of colorectal cancer cells with NTN-1 and with the adipocyte-derived secretome obtained from patients with obesity increased the migration of colorectal cancer cells. These results suggest that NTN-1 plays an important role in obesity-associated colon cancer development. Netrin (NTN)-1, an extracellular matrix protein with a crucial role in inflammation, is dysregulated during obesity (OB) and influences colon cancer (CC) progression. To decipher the mechanisms underlying CC development during obesity, we examined the expression of NTN1 and its receptors in the visceral adipose tissue (VAT) of 74 (25 normal weight (NW)) (16 with CC) and 49 patients with OB (12 with CC). We also evaluated the effect of caloric restriction (CR) on the gene expression levels of Ntn1 and its receptors in the colon from a rat model fed a normal diet. The impact of adipocyte-conditioned media (ACM) from patients with OB and NTN-1 was assessed on the expression levels of neogenin 1(NEO1), deleted in colorectal carcinomas (DCC) and uncoordinated-5 homolog B (UNC5B) in Caco-2 and HT-29 human colorectal cell lines, as well as on Caco-2 cell migration. Increased NTN1 and NEO1 mRNA levels in VAT were due to OB (p < 0.05) and CC (p < 0.001). In addition, an upregulation in the expression levels of DCC and UNC5B in patients with CC (p < 0.01 and p < 0.05, respectively) was observed. Decreased (p < 0.01) Ntn1 levels in the colon from rats submitted to CR were found. In vitro experiments showed that ACM increased DCC (p < 0.05) and NEO1 (p < 0.01) mRNA levels in HT-29 and Caco-2 cell lines, respectively, while UNC5B decreased (p < 0.01) in HT-29. The treatment with NTN-1 increased (p < 0.05) NEO1 mRNA levels in HT-29 cells and DCC (p < 0.05) in both cell lines. Finally, we revealed a potent migratory effect of ACM and NTN-1 on Caco-2 cells. Collectively, these findings point to increased NTN-1 during OB and CC fuelling cancer progression and exerting a strong migratory effect on colon cancer cells.
Revista:
COLORECTAL DISEASE
ISSN:
1462-8910
Año:
2023
Vol.:
25
N°:
5
Págs.:
1040 - 1041
Revista:
CIRUGIA ESPAÑOLA
ISSN:
0009-739X
Año:
2022
Vol.:
100
N°:
11
Págs.:
736 - 738
Revista:
SURGICAL LAPAROSCOPY ENDOSCOPY AND PERCUTANEOUS TECHNIQUES
ISSN:
1530-4515
Año:
2022
Vol.:
32
N°:
1
Págs.:
28 - 34
Background: Laparoscopic resection is the treatment of choice for colorectal cancer. Rates of conversion to open surgery range between 7% and 30% and controversy exists as to the effect of this on oncologic outcomes. The objective of this study was to analyze what factors are predictive of conversion and what effect they have on oncologic outcomes. Methods: From a prospective database of patients undergoing laparoscopic surgery between 2000 and 2018 a univariate and multivariate analyses were made of demographic, pathologic, and surgical variables together with complementary treatments comparing purely laparoscopic resection with conversions to open surgery. Overall and disease-free survival were compared using the Kaplan-Meier method. Results: Of a total of 829 patients, 43 (5.18%) converted to open surgery. In the univariate analysis, 12 variables were significantly associated with conversion, of which left-sided resection [odds ratio (OR): 2.908; P=0.02], resection of the rectum (OR: 4.749, P=0.014), and local invasion of the tumor (OR: 6.905, P<0.01) were independently predictive factors in the multiple logistic regression. Female sex was associated with fewer conversions (OR: 0.375, P=0.012). The incidence and pattern of relapses were similar in both groups and there were no significant differences between overall and disease-free survival. Conclusions: Left-sided resections, resections of the rectum and tumor invasion of neighboring structures are associated with higher rates of conversion. Female sex is associated with fewer conversions. Conversion to open surgery does not compromise oncologic outcomes at 5 and 10 years.
Revista:
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
ISSN:
1422-0067
Año:
2022
Vol.:
23
N°:
16
Págs.:
9222
Dysfunctional adipose tissue (AT) in the context of obesity leads to chronic inflammation together with an altered extracellular matrix (ECM) remodelling, favouring cancer development and progression. Recently, the influence of dermatopontin (DPT) in AT remodelling and inflammation has been proposed. We aimed to evaluate the role of DPT in the development of obesity-associated colon cancer (CC). Samples obtained from 73 subjects [26 lean (LN) and 47 with obesity (OB)] were used in a case-control study. Enrolled subjects were further subclassified according to the established diagnostic protocol for CC (42 without CC and 31 with CC). In vitro studies in the adenocarcinoma HT-29 cell line were performed to analyse the impact of pro- and anti-inflammatory mediators on the transcript levels of DPT as well as the effect of DPT on ECM remodelling and inflammation. Although obesity increased (p < 0.05) the circulating levels of DPT, its concentrations were significantly decreased (p < 0.05) in patients with CC. Gene expression levels of DPT in the colon from patients with CC were downregulated and, oppositely, a tendency towards increased mRNA levels in visceral AT was found. We further showed that DPT expression levels in HT-29 cells were enhanced (p < 0.05) by inflammatory factors (LPS, TNF-alpha and TGF-beta), whereas the anti-inflammatory IL-4 decreased (p < 0.05) its expression levels. We also demonstrated that DPT upregulated (p < 0.05) the mRNA of key molecules involved in ECM remodelling (COL1A1, COL5A3, TNC and VEGFA) whereas decorin (DCN) expression was downregulated (p < 0.05) in HT-29 cells. Finally, we revealed that the adipocyte-conditioned medium obtained from volunteers with OB enhanced (p < 0.01) the expression of DPT in HT-29 and Caco-2 cells. The decreased circulating and expression levels of DPT in the colon together with the tendency towards increased levels in visceral AT in patients with CC and its influence on the expression of ECM proteins suggest a possible role of DPT in the OB-associated CC.
Revista:
JOURNAL OF INFLAMMATION RESEARCH
ISSN:
1178-7031
Año:
2022
Vol.:
15
Págs.:
1331 - 1345
Background: Excess adiposity leads to a dysfunctional adipose tissue that contributes to the development of obesity-associated comorbidities such as type 2 diabetes (T2D). Interleukin-1 receptor antagonist (IL-1RA) is a naturally occurring antagonist of the IL-1 receptor with anti-inflammatory properties. The aim of the present study was to compare the circulating concentrations of IL-1RA and its mRNA expression in visceral adipose tissue (VAT) in subjects with normal weight (NW), obesity with normoglycemia (OB-NG), or obesity with impaired glucose tolerance or T2D (OB-IGT&T2D) and to analyze the effect of changes in body fat percentage (BF%) on IL-1RA levels. Methods: Serum concentrations of IL-1RA were measured in 156 volunteers. Expression of IL1RN mRNA in VAT obtained from 36 individuals was determined. In addition, the concentrations of IL-1RA were measured before and after weight gain as well as weight loss following a dietetic program or Roux-en-Y gastric bypass (RYGB). Results: Serum levels of IL-1RA were significantly increased in individuals with obesity, being further increased in the OBIGT&T2D group (NW 440 +/- 316, OB-NG 899 +/- 562, OB-IGT&T2D 1265 +/- 739 pg/mL; P<0.001) and associated with markers of inflammation and fatty liver. IL1RN mRNA expression in VAT was significantly increased in the OB-IGT&T2D group and correlated in the global cohort with the mRNA expression of SPP1, CCL2, CD68, and MMP9. Levels of IL-1RA were not modified after modest changes in BF%, but RYGB-induced weight loss significantly decreased IL-1RA concentrations from 1233 +/- 1009 to 660 +/- 538 pg/ mL (P<0.001). Conclusion: Serum IL-1RA concentrations are increased in patients with obesity being further elevated in obesity-associated IGT and T2D in association with markers of adipose tissue dysfunction. The mRNA expression of IL1RN is markedly increased in VAT of subjects with obesity and T2D in relation with genes involved in macrophage recruitment, inflammation and matrix remodeling. Serum IL-1RA concentrations are reduced when a notable amount of BF% is loss. Measurement of IL-1RA is an excellent biomarker of adipose tissue dysfunction in obesity-associated metabolic alterations.
Revista:
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
ISSN:
1422-0067
Año:
2021
Vol.:
22
N°:
16
Págs.:
8485
Objective: The protein microfibril-associated glycoprotein (MAGP)-1 constitutes a crucial extracellular matrix protein. We aimed to determine its impact on visceral adipose tissue (VAT) remodelling during obesity-associated colon cancer (CC). Methods: Samples obtained from 79 subjects (29 normoponderal (NP) (17 with CC) and 50 patients with obesity (OB) (19 with CC)) were used in the study. Circulating concentrations of MAGP-1 and its gene expression levels (MFAP2) in VAT were analysed. The impact of inflammation-related factors and adipocyte-conditioned media (ACM) on MFAP2 mRNA levels in colon adenocarcinoma HT-29 cells were further analysed. The effects of MAGP-1 in the expression of genes involved in the extracellular matrix (ECM) remodelling and tumorigenesis in HT-29 cells was also explored. Results: Obesity (p < 0.01) and CC (p < 0.001) significantly decreased MFAP2 gene expression levels in VAT whereas an opposite trend in TGFB1 mRNA levels was observed. Increased mRNA levels of MFAP2 after the stimulation of HT-29 cells with lipopolysaccharide (LPS) (p < 0.01) and interleukin (IL)-4 (p < 0.01) together with a downregulation (p < 0.05) after hypoxia mimicked by CoCl2 treatment was observed. MAGP-1 treatment significantly enhanced the mRNA levels of the ECM-remodelling genes collagen type 6 alpha 3 chain (COL6A3) (p < 0.05), decorin (DCN) (p < 0.01), osteopontin (SPP1) (p < 0.05) and TGFB1 (p < 0.05). Furthermore, MAGP-1 significantly reduced (p < 0.05) the gene expression levels of prostaglandin-endoperoxide synthase 2 (COX2/PTGS2), a key gene controlling cell proliferation, growth and adhesion in CC. Interestingly, a significant decrease (p < 0.01) in the mRNA levels of MFAP2 in HT-29 cells preincubated with ACM from volunteers with obesity compared with control media was observed. Conclusion: The decreased levels of MAGP-1 in patients with obesity and CC together with its capacity to modulate key genes involved in ECM remodelling and tumorigenesis suggest MAGP-1 as a link between AT excess and obesity-associated CC development.
Revista:
SCIENTIFIC REPORTS
ISSN:
2045-2322
Año:
2021
Vol.:
11
N°:
1
Págs.:
3992
EUS-guided anastomoses with LAMS have emerged as a therapeutic option for patients with obstruction of the digestive tract. However, the long-term permeability of these anastomoses remains unknown. Most of the published cases involve the gastric wall and experience in distal obstruction is limited to few case reports. We review our series of patients treated with LAMS for gastrointestinal obstruction and describe the technical success according to the anastomotic site and the long-term follow-up in those cases in which the stent migrated spontaneously or was removed. Out of 30 cases treated with LAMS, EUS-guided anastomosis did not involve the gastric wall in 6 patients. These procedures were technically more challenging as two failures were recorded (2/6, 33%) while technical success was achieved in 100% of the cases in which the stent was placed through the gastric wall. In two of the patients, one with entero-enteric and another with recto-colic anastomosis, stent removal after spontaneous displacement was followed by long term permeability of the EUS-guided anastomosis (172 and 234 days respectively). In a EUS-guided gastroenterostomy the stent was removed at 118 days, but closure of the fistula was confirmed 26 days later. Our experience suggests that LAMS placement between bowel loops is feasible and might allow the creation of an anastomosis with long-term patency. As compared to LAMS placement between bowel loops, when LAMS are placed through the gastric wall, removal of the LAMS seems to lead to closure of the fistula.
Revista:
SURGICAL LAPAROSCOPY ENDOSCOPY AND PERCUTANEOUS TECHNIQUES
ISSN:
1530-4515
Año:
2021
Vol.:
31
N°:
5
Págs.:
558 - 564
Background: Laparoscopic resection is the ideal treatment of colon cancer. The aim of the study was to analyze the predictive factors for postoperative complications and their impact on oncologic outcomes in laparoscopic resections in colon cancer.
Materials and Methods: In all patients undergoing elective laparoscopic surgery the number and degree of severity of postoperative complications were recorded and classified according to Clavien-Dindo. A univariate analysis was made of the demographic, surgical, and oncologic variables of patients with and without complications. The statistically significant variables were then entered into a multivariate model. In both groups overall and disease-free survival were analyzed using Kaplan-Meier estimates.
Results: Of 524 patients, 138 (26.3%) experienced some type of complication, 110 less severe (79.7%) and 28 (20.4%) severe. Twenty-nine conversions to open surgery occurred (5.5%) and hospital mortality was 0.2%. In the multivariate analysis, use of corticosteroids [odds ratio (OR): 3.619], oral anticoagulants (OR: 3.49), blood transfusions (OR: 4.30), and conversion to open surgery (OR: 3.93) were significantly associated with the development of complications. However, sigmoid resections were associated with fewer complications (OR: 0.45). Overall 5-year and 10-year survival in both groups, was 83.3%, 74.1%, 76.0%, and 67.1%, respectively (P = 0.18). Disease-free survival at 5 and 10 years, excluding stage IV tumors, was 88.6% and 90.4%, respectively (P = 0.881).
Conclusions: The use of corticosteroids, oral anticoagulants, blood transfusions, and conversion to open surgery are all independent predictive factors of postoperative complications. Sigmoid resections are associated with fewer complications. In laparoscopic resections of the colon, complications do not negatively affect long-term oncologic outcomes.
Revista:
COLORECTAL DISEASE
ISSN:
1462-8910
Año:
2021
Vol.:
23
N°:
6
Págs.:
1588 - 1589
Revista:
JOURNAL OF INFLAMMATION RESEARCH
ISSN:
1178-7031
Año:
2021
Vol.:
14
Págs.:
6431 - 6446
Background: Inflammasomes maintain tissue homeostasis and their altered regulation in the colon, and the adipose tissue (AT) leads to chronic activation of inflammatory pathways promoting colon cancer (CC) development. We aimed to analyze the potential involvement of inflammasomes in obesity-associated CC. Methods: Ninety-nine volunteers [61 with obesity (OB) and 38 normoponderal (NP)] further subclassified according to the approved protocol for the diagnosis of CC (58 without CC and 41 with CC) were included in the case-control study. Results: CC (P<0.01) and obesity (P<0.01) were accompanied by increased mRNA levels of NLRP3, NLRP6, ASC, IL1B and NOD2 in VAT. Contrarily, patients with CC exhibited a downregulation of NLRP6 and IL18 in their colon. Additionally, we revealed that the decreased Nlrp1 (P<0.05), Nlrp3 (P<0.01) and Nlrp6 (P<0.01) mRNA levels in the colon from obese rats significantly increase (P<0.05) after caloric restriction. Adipocyteconditioned media obtained from subjects with obesity reduced (P<0.01) the mRNA of NLRP3 as well as molecules involved in maintaining the intestinal integrity (MUC2, CLDN1 and TJP1) and the anti-inflammatory factors FGF21, KLF4, and IL33 and in HT 29 cells. We also found that the knockdown of NLRP6 in HT-29 cells significantly upregulated (P<0.05) the mRNA of NLRP1 and NLRP3 and inhibited (P<0.05) the expression levels of MUC2. Finally, we showed that the incubation of HT-29 with Akkermansia muciniphila influence (P<0.05) the inflammasome expression profile as well as intestinal integrity-related genes and aberrant inflammation. Conclusions: These findings provide evidence that the downregulated levels of NLRP6 and IL18 in the colon from patients with CC may be responsible for a reduced intestinal-barrier integrity, triggering local inflammation, which in turn acts on the dysfunctional AT in obesity, increasing the expression of different inflammasome components and flaring up a vicious cycle of uncontrollable inflammatory cascades that favours a pro-tumorigenic microenvironment.
Autores:
Tejedor, P. (Autor de correspondencia); Simo, V.; Arredondo, J.; et al.
Revista:
REVISTA ESPAÑOLA DE ENFERMEDADES DIGESTIVAS
ISSN:
1130-0108
Año:
2021
Vol.:
113
N°:
2
Págs.:
85 - 91
Objective: the aim of the study was to analyze the management of colorectal cancer (CRC) patients diagnosed with CRC or undergoing elective surgery during the period of the SARS-CoV-2 pandemic. Material and methods: a multicenter ambispective analysis was performed in nine centers in Spain during a four-month period. Data were collected from every patient, including changes in treatments, referrals or delays in surgeries, changes in surgical approaches, postoperative outcomes and perioperative SARS-CoV-2 status. The hospital's response to the outbreak and available resources were categorized, and outcomes were divided into periods based on the timeline of the pandemic. Results: a total of 301 patients were included by the study centers and 259 (86 %) underwent surgery. Five hospitals went into phase III during the peak of incidence period, one remained in phase II and three in phase I. More than 60 % of patients suffered some form of change: 48 % referrals, 39 % delays, 4% of rectal cancer patients had a prolonged interval to surgery and 5 % underwent neoadjuvant treatment. At the time of study closure, 3 % did not undergo surgery. More than 85 % of the patients were tested preoperatively for SARS-CoV-2. A total of nine patients (3 %) developed postoperative pneumonia; three of them had confirmed SARS-CoV-2. The observed surgical complications and mortality rates were similar as expected in a usual situation. Conclusions: the present multicenter study shows different patterns of response to the SARS-CoV-2 pandemic and collateral effects in managing CRC patients. Knowing these patterns could be useful for planning future changes in surgical departments in preparation for new outbreaks.
Autores:
Garcia-Arranz, M. (Autor de correspondencia); Garda-Olmo, D.; Herreros, M. D.; et al.
Revista:
STEM CELLS TRANSLATIONAL MEDICINE
ISSN:
2157-6564
Año:
2020
Vol.:
9
N°:
3
Págs.:
295 - 301
The aim of this clinical trial (ID Number NCT01803347) was to determine the safety and efficacy of autologous adipose-derived stem cells (ASCs) for treatment of cryptoglandular fistula. This research was conducted following an analysis of the mistakes of a same previous phase III clinical trial. We designed a multicenter, randomized, single-blind clinical trial, recruiting 57 patients. Forty-four patients were categorized as belonging to the intent-to-treat group. Of these, 23 patients received 100 million ASCs plus intralesional fibrin glue (group A) and 21 received intralesional fibrin glue (group B), both after a deeper curettage of tracks and closure of internal openings. Fistula healing was defined as complete re-epithelialization of external openings. Those patients in whom the fistula had not healed after 16 weeks were eligible for retreatment. Patients were evaluated at 1, 4, 16, 36, and 52 weeks and 2 years after treatment. Results were assessed by an evaluator blinded to the type of treatment. After 16 weeks, the healing rate was 30.4% in group A and 42.8% in group B, rising to 55.0% and 63.1%, respectively, at 52 weeks. At the end of the study (2 years after treatment), the healing rate remained at 50.0% in group A and had reduced to 26.3% in group B. The safety of the cellular treatment was confirmed and no impact on fecal continence was detected. The main conclusion was that autologous ASCs for the treatment of cryptoglandular perianal fistula is safe and can favor long-term and sustained fistula healing.
Revista:
JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS
ISSN:
1072-7515
Año:
2020
Vol.:
231
N°:
6
Págs.:
E11 - E14
Revista:
REVISTA ESPAÑOLA DE ENFERMEDADES DIGESTIVAS
ISSN:
1130-0108
Año:
2020
Vol.:
112
N°:
1
Págs.:
16 - 22
Background: the standard treatment for locally advanced rectal cancer is neoadjuvant chemo-radiotherapy, surgery and adjuvant chemotherapy. Only 50% of patients receive the adjuvant treatment due to the surgical complications and toxicity of radiotherapy. Recently, neoadjuvant chemotherapy has been investigated in the locally advanced rectal cancer setting, with the aim of guaranteeing an uninterrupted systemic treatment. The objective of the present study was to assess the safety and efficacy of neoadjuvant chemotherapy in locally advanced rectal cancer.
Methods and patients: patients treated with neoadjuvant chemotherapy and surgery were identified from a prospective database of patients with rectal cancer (cII-III). The primary outcomes were the assessment of the number of R0 resections, the degree of pathologic response, patterns of recurrence and overall and disease-free survival. Treatment schedule: patients received 6-8 cycles of oxaliplatin and fluoropyrimides based chemotherapy.
Results: twenty-seven patients who received neoadjuvant chemotherapy were identified. Twenty-six anterior resections and one Hartmann intervention were performed. An R0 resection was performed in 27 (100%) patients and no involvement of the circumferential margin was observed. Complete pathologic response (ypT0N0) was confirmed in four (14.8%) patients.The median follow-up was 35 months (range: 10-81) and four distant recurrences were recorded. Overall and disease-free survival at five years was 85% and 84.7%, respectively. Twenty-seven (100%) patients received all the cycles of chemotherapy, with a mean of six cycles (range 5-8) per patient.
Conclusions: neoadjuvant chemotherapy is a promising alternative in the locally advanced rectal cancer setting and further phase III clinical trials are clearly warranted.
Revista:
REVISTA ESPAÑOLA DE ENFERMEDADES DIGESTIVAS
ISSN:
1130-0108
Año:
2020
Vol.:
112
N°:
8
Págs.:
609 - 614
Background: the prognostic value of the number of lymph nodes isolated (< 12 versus >= 12) in the surgical specimen continues to be controversial. In this study, the impact of isolating fewer or more than 12 lymph nodes in stage II colon cancer with a high-risk biologic phenotype was analyzed, such as the presence of perineural invasion.
Methods: all cases of stage II disease (T3-4N0M0) with perineural invasion (PNI+) were retrospectively identified from a prospective database of patients undergoing surgery for colon cancer. The cohort was divided into two groups depending on the number of lymph nodes isolated (< 12 vs >= 12). Apart from clinical and surgical data, the patterns of recurrence, overall (OS) and disease-free survival (DFS) at five and ten years were analyzed.
Results: sixty patients met the inclusion criteria, 31.7 % had < 12 lymph nodes isolated and 68.3 % had more than 12 isolated. There were no clinical or surgical differences between the two groups. OS at five and ten years was significantly lower in the patients with < 12 lymph nodes isolated (84.2 %, 62.7 % vs 94.6 % and 91.6 %, p = 0.01). DFS at five and ten years was 51 % vs 86.5 %, respectively (p = 0.005).
Conclusion: the number of lymph nodes isolated (with a cutoff of 12) in stage II colon cancer with PNI+ has prognostic value and should therefore be borne in mind when planning adjuvant chemotherapy.
Revista:
REVISTA ESPAÑOLA DE ENFERMEDADES DIGESTIVAS
ISSN:
1130-0108
Año:
2018
Vol.:
110
N°:
3
Págs.:
138 - 144
Purpose: The objective of the study was to analyze the clinico-pathological differences and the oncologic outcomes between right and left-sided colon cancer. Patients and methods: The patients cohort was identified from a prospective register of colon cancer, 950 patients underwent surgery (stages I, II and III), of which 431 had right-sided colon cancer and 519 had left-sided colon cancer. Results: More laparoscopic resections were performed (101 vs 191; p < 0.001) and operating times were longer (146 min vs 165 min; p < 0.001) in the left-sided colon group. Patients with right-sided colon cancer more frequently received transfusions (18.8% vs 11.3%; p < 0.001) and experienced a greater number of complications (28.5% vs 20.9%, p = 0.004), although severity and operative mortality were similar in both groups (1.2% vs 0.2%). Mucinous adenocarcinomas and undifferentiated tumors were more frequent in the right-sided group (12% vs 6.5%; p < 0.001). Early stage was predominant in the left-sided colon tumors (28.2% vs 34.5%, p = 0.02). There were no differences in disease-free survival (DFS) in stages I and II after a median follow-up of 103 months. However, a greater survival at five and ten years in left-sided, stage III tumors was observed, with a trend towards statistical significance (p = 0.06). No differences were found with regard to the patterns of recurrence. Conclusions: Right-sided colon cancer exhibits phenotypical differences with regard to left-sided colon cancer. In stage III disease, left-sided colon cancer has a greater survival with a trend towards statistical significance. Overall, tumor location is a variable that should be taken into consideration in clinical studies of colon cancer.
Revista:
REVISTA ESPAÑOLA DE ENFERMEDADES DIGESTIVAS
ISSN:
1130-0108
Año:
2018
Vol.:
110
N°:
11
Págs.:
684 - 690
Purpose: the aim of this study was to compare overall and disease-free survival among patients with colorectal cancer detected via a screening program as compared to those with symptomatic cancer.
Material and methods: patients diagnosed via colonoscopy (screening group) and those with clinical symptoms (non-screening) were identified from 1995 to 2014. Demographic, clinical, surgical and pathologic variables were recorded. Stage I, II and III cancers were included. Overall and disease-free survival were calculated at five and ten years after tumor resection and survival was calculated by matching both groups for cancers at stage I, II and III.
Results: two hundred and fifty patients were identified as a result of screening procedures and 1,330 patients presented with symptomatic cancers.There were no significant differences in the baseline characteristics between the two groups. Pathologic stage, degree of differentiation, perineural invasion and lymphovascular invasion were lower in the screening group (p < 0.01). Overall and disease-free survival at five and ten years were higher in the screening group (p < 0.01). However, when the subjects were matched for pathologic stage, significant differences were found between the two groups with regard to stage I and III tumors. Disease-free survival in stage III at five years (79.1 vs 61.7%; p < 0.001) and ten years (79.1% vs 58.5%; p < 0.001) were significantly higher in the screening group.
Conclusions: patients with stage I and III tumors that were diagnosed via a screening program have a higher overall and disease-free survival at five and ten years.
Revista:
INTERNATIONAL JOURNAL OF SURGERY
ISSN:
1743-9191
Año:
2018
Vol.:
52
Págs.:
303 - 308
Purpose: The objective is to analyze the impact of severe postoperative complications in patients undergoing curative surgery for colon cancer. Material and methods: From a prospective database, we identified patients with stage I-III disease (AJCC) who underwent surgery between 2000 and 2014. Patients were selected with major complications (IIIb on the Clavien-Dindo classification) and with no major complications. Variables were analyzed in both groups. Local, peritoneal and distant recurrence together with overall survival and disease-free survival were analyzed. Results: Of a total of 950 patients, 51 (5.3%) experienced major complications. Operative mortality was 2.6%. Age, ASA grade, urgent surgery, pre-operative hemoglobin, right-sided location, operative time, transfusion, conversion to open surgery, were all associated with major complications (all P < 0.05). With a median follow-up of 84.8 and 40 months in both groups, there was greater incidence of local recurrences in patients experiencing complications (2.4% vs 7.8%; P=0.03 OR 3.39, 95% CI 1.12-10.24), being more marked in stage III patients (4.2% vs 21%; P=0.005, OR 6.13 95% CI 1.74-21.56). In the stage III group, peritoneal recurrence was significantly greater in patients with complications (13.6% vs 31.6%; P=0.04 OR 2.92 95% CI 1.04-8.18). Patients with major complications had a significantly lower overall survival (P=0.024) than patients with no complications both at 5 years (78.9% vs 68.8%) and 10 years (74.6% vs 32.1%). The same trend was observed for disease-free survival (71.6% vs 48.3% and 69.8% vs 32.2%; P=0.013). Conclusion: The development of major complications following colectomy for colon cancer has a negative impact on long-term oncologic outcomes, especially in stage III disease.
Revista:
ONCOIMMUNOLOGY
ISSN:
2162-402X
Año:
2017
Vol.:
6
N°:
7
Págs.:
e1328338
Growing evidence indicates that adipose tissue inflammation is an important mechanism whereby obesity promotes cancer risk and progression. Since IL-32 is an important inflammatory and remodeling factor in obesity and is also related to colon cancer (CC) development, the aim of this study was to explore whether IL-32 could function as an inflammatory factor in human obesity-associated CC promoting a microenvironment favorable for tumor growth. Samples obtained from 84 subjects [27 lean (LN) and 57 obese (OB)] were used in the study. Enrolled subjects were further subclassified according to the established diagnostic protocol for CC (49 without CC and 35 with CC). We show, for the first time, that obesity (p = 0.009) and CC (p = 0.026) increase circulating concentrations of IL-32¿. Consistently, we further showed that gene (p < 0.05) and protein (p < 0.01) expression levels of IL-32¿ were upregulated in VAT from obese patients with CC. Additionally, we revealed that IL32 expression levels are enhanced by hypoxia and inflammation-related factors in HT-29 CC cells as well as that IL-32¿ is involved in the upregulation of inflammation (IL8, TNF, and CCL2) and extracellular matrix (ECM) remodeling (SPP1 and MMP9) genes in HT-29 cancer cells. Additionally, we also demonstrate that the adipocyte-conditioned medium obtained from obese patients stimulates (p < 0.05) the expression of IL32 in human CC cells. These findings provide evidence of the potential involvement of IL-32 in the development of obesity-associated CC as a pro-inflammatory and ECM remodeling cytokine.
Autores:
Arredondo, J.; Baixauli, J; Pastor, C.; et al.
Revista:
CLINICAL AND TRANSLATIONAL ONCOLOGY
ISSN:
1699-048X
Año:
2017
Vol.:
19
N°:
3
Págs.:
379 - 385
Neoadjuvant chemotherapy is being actively tested as an emerging alternative for the treatment of locally advanced colon cancer (LACC) patients, resembling its use in other gastrointestinal tumors. This study assesses the mid-term oncologic outcome of LACC patients treated with oxaliplatin and fluoropyrimidines-based preoperative chemotherapy followed by surgery. Patients with radiologically resectable LACC treated with neoadjuvant therapy between 2009 and 2014 were retrospectively analyzed. Radiological, metabolic, and pathological tumor response was assessed. Both postoperative complications, relapse-free survival (RFS), and overall survival (OS) were studied. Sixty-five LACC patients who received treatment were included. Planned treatment was completed by 93.8 % of patients. All patients underwent surgery without delay. The median time between the start of chemotherapy and surgery was 71 days (65-82). No progressive disease was observed during preoperative treatment. A statistically significant tumor volume reduction of 62.5 % was achieved by CT scan (39.8-79.8) (p < 0.001). It was also observed a median reduction of 40.5 % (24.2-63.7 %) (p < 0.005) of SUVmax (Standard Uptake Value) by PET-CT scan. Complete pathologic response was achieved in 4.6 % of patients. Postoperative complications were observed in 15.4 % of patients, with no cases of mortality. After a median follow-up of 40.1 months, (p (25)-p (75): 27.3-57.8) 3-5 year actuarial RFS was 88.9-85.6 %, respectively. Five-year actuarial OS was 95.3 %. Preoperative chemotherapy in LACC patients is safe and able to induce major tumor regression. Survival times are encouraging, and further research seems warranted.
Revista:
ANNALS OF SURGICAL ONCOLOGY
ISSN:
1068-9265
Año:
2017
Vol.:
24
N°:
4
Págs.:
1077 - 1084
Background. Perineural invasion (PNI) in colon cancer (CC) has been associated with poorer prognosis even in stage II disease (T3-4 N0 M0). The aim of this study is to analyze prognostic histopathologic factors in stage II colon cancer in patients treated with curative surgery as established in National Comprehensive Cancer Network guidelines. Methods. From a prospective database of CC cases, 507 patients with stage I-II disease who had undergone curative resection from January 2000 and December 2012 were identified. Of these patients, 17 % received 5-flurouracil-based adjuvant chemotherapy. Together with demographic and anatomic variables, we also studied perineural and lymphovascular invasion, degree of differentiation, and their correlation with disease-free survival. Results. Perineural invasion was identified in 57 patients (11.2 %) and lymphovascular invasion (LVI) in 82 (16.2 %) of the 507 patients. Perineural invasion was associated with LVI, the depth of invasion of the wall of the colon, and location of the tumor. Overall and disease-free survival of the complete series at 5 and 10 years was 89.5, 85.2, 83.2 and 81.6 %, respectively. In the PNI positive patients, disease-free survival at 5 years was significantly lower than in those without PNI (73.5 vs 88.6 %; p = 0.02). Multivariate analysis showed the presence of PNI to be a significant independent prognostic factor for disease-free survival (p = 0.025). Adjuvant chemotherapy reversed the impact of PNI on 5-to 10-year disease-free survival. Conclusions. PNI a major prognostic and predictive factor in stage II colon cancer, and our results support the use of adjuvant chemotherapy in patients with PNI.
Revista:
REVISTA ESPAÑOLA DE ENFERMEDADES DIGESTIVAS
ISSN:
1130-0108
Año:
2017
Vol.:
109
N°:
11
Págs.:
802 - 802
Revista:
CLINICAL AND TRANSLATIONAL ONCOLOGY
ISSN:
1699-048X
Año:
2016
Vol.:
18
N°:
7
Págs.:
714-721
Our results suggest that cellular mucin pools are an indicator of an aggressive phenotype and harbingers of a worse prognosis.
Revista:
PLOS ONE
ISSN:
1932-6203
Año:
2016
Vol.:
11
N°:
9
Págs.:
e0162189
To our knowledge, we herein show for the first time that obese patients with CC exhibit increased circulating levels of OPN, YKL-40 and TNC providing further evidence for the influence of obesity on CC development via ECM proteins, representing promising diagnostic biomarkers or target molecules for therapeutics.
Revista:
CLINICAL AND TRANSLATIONAL ONCOLOGY
ISSN:
1699-048X
Año:
2016
Vol.:
18
N°:
9
Págs.:
909-914
Combined treatment for LARC obtains a 5-year OS rounding 90 %. Follow-up based on thoracic-abdominal CT scan allows an early diagnosis of metastatic lesions. Surgical resection of metastases, regardless of their location, greatly increases the patient's survival rate.
Revista:
INTERNATIONAL UROGYNECOLOGY JOURNAL
ISSN:
0937-3462
Año:
2015
Vol.:
26
N°:
7
Págs.:
985-990
Levator avulsion is associated with lower manometric squeeze pressure (p¿=¿0.032).
Revista:
ANNALS OF SURGICAL ONCOLOGY
ISSN:
1068-9265
Año:
2015
Vol.:
22
N°:
3
Págs.:
916-923
The presence of PLVI is a more powerful prognostic factor than TRG in LARC patients treated with neoadjuvant CRT followed by surgery. PLVI denotes an aggressive phenotype, suggesting that these patients may benefit from adjuvant systemic therapy.
Revista:
INTERNATIONAL JOURNAL OF COLORECTAL DISEASE
ISSN:
0179-1958
Año:
2015
Vol.:
30
N°:
10
Págs.:
1427 - 1428
Revista:
CIRUGIA ESPAÑOLA
ISSN:
0009-739X
Año:
2015
Vol.:
93
N°:
3
Págs.:
207 - 208
Como señalan García-Granero et al.3, tras 30 años de progresos técnicos en el tratamiento del CRLA, además de la cirugía correcta, debemos tratar la enfermedad sistémica ¿micrometástasis, células tumorales circulantes¿ precozmente en los casos de alto riesgo, como es el tercio distal del recto
Revista:
REVISTA ESPAÑOLA DE ENFERMEDADES DIGESTIVAS
ISSN:
1130-0108
Año:
2015
Vol.:
107
N°:
6
Págs.:
340-346
With a mean follow-up of 70.06 months, local recurrence was 4.8% and distant recurrence 25.5%. No differences were found in the histopathologic prognostic factors across the three groups studied depending on distance (cm) from the anal margin. Involvement of the circumferential resection margin (CRM+) was significantly greater in tumors in the distal third of the rectum (8.5%; p = 0.04). 67 patients (13.4%) showed a complete pathologic response. DSF at 5 and 10 years was significantly lower in patients with tumors affecting the distal third as compared to the middle third of the rectum (61.9% vs. 57.7%; p = 0.04). Tumors at this distal location resulted in a significantly higher incidence of lung metastases (p = 0.016).
Revista:
JOURNAL OF GASTROINTESTINAL ONCOLOGY
ISSN:
2078-6891
Año:
2014
Vol.:
5
N°:
2
Págs.:
148-153
Neoadjuvant chemotherapy as a systemic treatment for stage IV colon cancer does not indicate surgery contraindication nor increases postoperative morbimortality by a significant amount.
Revista:
SURGERY TODAY
ISSN:
0941-1291
Año:
2014
Vol.:
44
N°:
12
Págs.:
2318-2323
If longer-term follow-up is achieved, definitive conclusions may be obtained. However, the present results suggest that the cleft lift procedure may become the gold standard technique for the surgical management of non-acute pilonidal disease.
Revista:
REVISTA ESPAÑOLA DE ENFERMEDADES DIGESTIVAS
ISSN:
1130-0108
Año:
2014
Vol.:
106
N°:
3
Págs.:
171 - 194
Liver regeneration (LR) is one of the most amazing tissue injury response. Given its therapeutic significance has been deeply studied in the last decades.LR is an extraordinary complex process, strictly regulated, which accomplishes the characteristics of the most evolutionary biologic systems (robustness) and explains the difficulties of reshaping it with therapeutic goals.TH reproduces the physiological tissue damage response pattern, with a first phase of priming of the hepatocytes-cell-cycle transition G0-G1¿, and a second phase of proliferation ¿cell-cycleS/M phases¿ which ends with the liver mass recovering. This process has been related with the tissue injury response regulators as: complement system, platelets, inflammatory cytokines(TNF-a, IL-1b, IL-6), growth factors (HGF, EGF, VGF) and anti-inflammatory factors (IL-10, TGF-b).Given its complexity and strict regulation, illustrates the unique alternative to liver failure is liver transplantation.The recent induced pluripotential cells (iPS) description and the mesenchymal stem cell (CD133+) plastic capability have aroused new prospects in the cellular therapy field. Those works have assured the cooperation between mesenchymal and epithelial cells. Herein, we review the physiologic mechanisms of liver regeneration.
Revista:
ANALES DE PEDIATRIA
ISSN:
1695-4033
Año:
2014
Vol.:
80
N°:
5
Págs.:
339
Revista:
ANALES DE PEDIATRIA
ISSN:
1695-4033
Año:
2014
Vol.:
80
N°:
5
Págs.:
339
Con la experiencia de grupos como el de Pareja et al. y las contribuciones recientes de la plasticidad de las iPSC, se abre una nueva era en la terapia celular en el tratamiento de los errores congénitos del metabolismo.
Revista:
REVISTA ESPAÑOLA DE ENFERMEDADES DIGESTIVAS
ISSN:
1130-0108
Año:
2014
Vol.:
106
N°:
7
Págs.:
497 - 499
A 36-year-old woman without previous medical history presented at the emergency room with recent onset of diffuse, continuous abdominal pain associated to nausea without vomiting.On examination, her abdomen was soft, very distended and tender with guarding over the left iliac fossa.
Her blood tests were normal apart from a white cell count of 17,2x109/L. Abdominal radiograph findings showed suggestive images of CV, confirmed on computerized tomography (CT) (Fig. 1). We decided to perform a colonoscopy to decompress the colon before surgery. After that, her abdomen became non-distended and was taken to the operating room.Under laparoscopic approach (three 5 mm trocars), we found a soft but not dilated ascending colon that lacked retroperitoneal fixation. It was fixed in its proper place with three running sutures
Revista:
JOURNAL OF GASTROINTESTINAL ONCOLOGY
ISSN:
2078-6891
Año:
2014
Vol.:
5
N°:
2
Págs.:
104-111
Oxaliplatin/fluorpyrimidine neoadjuvant chemotherapy induces major tumour shrinkage at both the pathological and radiological levels. The CT scan shows a high accuracy and a low overstaged rate in LACC patients treated by means of a neoadjuvant approach.
Revista:
COLORECTAL DISEASE
ISSN:
1462-8910
Año:
2013
Vol.:
15
N°:
5
Págs.:
552-27
Neoadjuvant chemotherapy followed by surgery and chemotherapy for LACC is safe without apparent increase of early and medium-term complications
Revista:
DISEASES OF THE COLON AND RECTUM
ISSN:
0012-3706
Año:
2013
Vol.:
56
N°:
4
Págs.:
416-421
Patients with low third locally advanced rectal cancer with a poor response to neoadjuvant chemoradiotherapy (high y-pathological stage or low tumor regression grade) are at high risk of recurrence. Intense surveillance and the design of alternative therapeutic approaches aimed to lower the distant failure rate seem warranted.
Revista:
INTERNATIONAL JOURNAL OF COLORECTAL DISEASE
ISSN:
0179-1958
Año:
2013
Vol.:
28
N°:
5
Págs.:
671 - 677
Revista:
GASTROENTEROLOGIA Y HEPATOLOGIA
ISSN:
0210-5705
Año:
2012
Vol.:
35
N°:
9
Págs.:
675
Las descripciones de discretas mejoras en la función hepática, en modelos experimentales y en la práctica clínica, tras la perfusión de células progenitoras de MO pudieran estar en relación con los propios mecanismos innatos de respuesta al estrés o daño celular descritos por Matzinger9 y Medzhitov10 . Es llamativo que se requiera la inducción de un «daño» hepatocelular previo (homing) para garantizar la viabilidad de las células trasplantadas.
Revista:
REVISTA ESPAÑOLA DE ENFERMEDADES DIGESTIVAS
ISSN:
1130-0108
Año:
2012
Vol.:
104
N°:
8
Págs.:
436-439
the duodenal defect repair with a patch of the remant antrum, represents a valid alternative in similar circumstances. To our knowledge, it appears to be the first clinical description of this technique.
Revista:
DISEASES OF THE COLON AND RECTUM
ISSN:
0012-3706
Año:
2011
Vol.:
54
N°:
9
Págs.:
1141 -6
Endoscopic ultrasound allows prediction of involved lymph nodes in 75% of the cases; however, 1 in 5 patients are missclassified as uN0 after neoadjuvant treatment. In our point of view, this percentage is too high to rely only on this diagnostic modality
Revista:
CIRUGIA ESPAÑOLA
ISSN:
0009-739X
Año:
2011
Vol.:
89
N°:
1
Págs.:
24-30
La anastomosis intracorpórea frente a la extracorpórea en la hemicolectomía derecha laparoscópica permite obtener un mayor número de ganglios resecados y un inicio más precoz de la tolerancia oral y del tránsito intestinal.
Revista:
International Journal of Gynecolgical Cancer
ISSN:
1048-891X
Año:
2011
Vol.:
21
N°:
2
Págs.:
397 - 402
Revista:
REVISTA ESPAÑOLA DE ENFERMEDADES DIGESTIVAS
ISSN:
1130-0108
Año:
2011
Vol.:
103
N°:
2
Págs.:
107-108
Revista:
JOURNAL OF NUTRITIONAL BIOCHEMISTRY
ISSN:
0955-2863
Año:
2011
Vol.:
22
N°:
7
Págs.:
634 - 641