Telomere Length as a New Risk Marker of Early-Onset Colorectal Cancer.

Early-onset colorectal cancer (EOCRC; age younger than 50 years) incidence has been steadily increasing in recent decades worldwide. The need for new biomarkers for EOCRC prevention strategies is undeniable. In this study, we aimed to explore whether an aging factor, such as telomere length (TL), could be a useful tool in EOCRC screening. The absolute leukocyte TL from 87 microsatellite stable EOCRC patients and 109 healthy controls (HC) with the same range of age, was quantified by Real Time Quantitative PCR (RT-qPCR). Then, leukocyte whole-exome sequencing (WES) was performed to study the status of the genes involved in TL maintenance (hTERT, TERC, DKC1, TERF1, TERF2, TERF2IP, TINF2, ACD, and POT1) in 70 sporadic EOCRC cases from the original cohort. We observed that TL was significantly shorter in EOCRC patients than in healthy individuals (EOCRC mean: 122 kb vs. HC mean: 296 kb; p < 0.001), suggesting that telomeric shortening could be associated with EOCRC susceptibility. In addition, we found a significant association between several SNPs of hTERT (rs79662648), POT1 (rs76436625, rs10263573, rs3815221, rs7794637, rs7784168, rs4383910, and rs7782354), TERF2 (rs251796 and rs344152214), and TERF2IP (rs7205764) genes and the risk of developing EOCRC. We consider that the measurement of germline TL and the status analysis of telomere maintenance related genes polymorphisms at early ages could be non-invasive methods that could facilitate the early identification of individuals at risk of developing EOCRC.

Familial component of early-onset colorectal cancer: opportunity for prevention.

BACKGROUND: Individuals with a non-syndromic family history of colorectal cancer are known to have an increased risk. There is an opportunity to prevent early-onset colorectal cancer (age less than 50 years) (EOCRC) in this population. The aim was to explore the proportion of EOCRC that is preventable due to family history of colorectal cancer. METHODS: This was a retrospective multicentre European study of patients with non-hereditary EOCRC. The impact of the European Society of Gastrointestinal Endoscopy (ESGE), U.S. Multi-Society Task Force (USMSTF), and National Comprehensive Cancer Network (NCCN) guidelines on prevention and early diagnosis was compared. Colorectal cancer was defined as potentially preventable if surveillance colonoscopy would have been performed at least 5 years before the age of diagnosis of colorectal cancer, and diagnosed early if colonoscopy was undertaken between 1 and 4 years before the diagnosis. RESULTS: Some 903 patients with EOCRC were included. Criteria for familial colorectal cancer risk in ESGE, USMSTF, and NCCN guidelines were met in 6.3, 9.4, and 30.4 per cent of patients respectively. Based on ESGE, USMSTF, and NCCN guidelines, colorectal cancer could potentially have been prevented in 41, 55, and 30.3 per cent of patients, and diagnosed earlier in 11, 14, and 21.1 per cent respectively. In ESGE guidelines, if surveillance had started 10 years before the youngest relative, there would be a significant increase in prevention (41 versus 55 per cent; P = 0.010). CONCLUSION: ESGE, USMSTF, and NCCN criteria for familial colorectal cancer were met in 6.3, 9.4, and 30.4 per cent of patients with EOCRC respectively. In these patients, early detection and/or prevention could be achieved in 52, 70, and 51.4 per cent respectively. Early and accurate identification of familial colorectal cancer risk and increase in the uptake of early colonoscopy are key to decreasing familial EOCRC.

Oncological outcome of wide anatomic resection with partial mesorectal excision in patients with upper and middle rectal cancer.

AIM: The aim was to investigate the influence of distal resection margin and extent of mesorectal excision on long-term oncological outcomes. METHOD: Consecutive patients with upper and middle third rectal cancer from June 2006 to February 2016 were reviewed. Patients were divided into four groups depending on the distal margin considered as a surrogate marker of the extension of mesorectal excision (Q1 ≤10 mm, Q2 11-20 mm, Q3 21-30 mm, Q4 ≥31 mm). Local-recurrence-free survival (LRFS), disease-free survival (DFS) and overall survival (OS) were estimated. Cox regression models were used to investigate the influence of surgical and clinicopathological variables on prognosis by adjusting for confounding factors. RESULTS: Two hundred and eleven patients with mid (125) and upper (86) rectal cancer underwent wide mesorectal excision. The median follow-up was 48.64 months (interquartile range 28-63). 17.5% patients developed recurrence. The 5-year LRFS, DFS and OS for all patients were 93.20%, 83.89% and 80.1%, respectively, with no statistically significant differences between groups (LRFS, P = 0.601; DFS, P = 0.487; OS, P = 0.468). In the multivariable analysis the recurrences and survival were associated with the quality of the mesorectum (LRFS, hazard ratio 10.629, 95% CI 2.324-48.610, P = 0.002; DFS, hazard ratio 2.789, 95% CI 1.314-5.922, P = 0.008). CONCLUSION: A wide anatomical resection with partial mesorectal excision and shorter distal resection margin does not jeopardize the oncological outcomes.

Transanal Hartmann's colostomy reversal assisted by laparoscopy: outcomes of the first 10 patients.

INTRODUCTION: Restoration of intestinal continuity after Hartmann's procedure is a technically difficult surgery associated with significant morbidity and mortality. This study presents the short-term results of a new approach: a transanal Hartmann's colostomy reversal assisted by laparoscopy. METHOD: This is a retrospective analysis of data collected in one tertiary hospital, from October 2013 to November 2015. RESULTS: During the study period, there were ten cases of transanal Hartmann's reversal. Reasons for Hartmann's procedure were: complicated diverticulitis (4), anastomotic leak (3), and recto-sigmoid cancer (3). Rectal stump length was 10.4 ± 4.5 cm. Reconstruction was achieved in all patients. One low colorectal anastomosis was hand-sewn, the other 9 were stapled. Mean operative time was 204 ± 65 min. Diverting loop ileostomies were created in five patients and all were closed during the following year. One case required hand-assistance but there was no conversion to open surgery. Iatrogenic laparoscopic enterotomies occurred in four patients and all were repaired primarily without consequences. Three patients had a total of four post-operative complications: ileus (2), abdominal abscess and wound infection (1). None required reoperation. Mean length of stay was 7.2 ± 4.3 days. One required readmission. CONCLUSION: A transanal Hartmann's reversal assisted by laparoscopy is a new approach for a difficult surgery. It has the potential to be an additional tool in the case of hostile pelvises or with a rectal stump difficult to identify. The surgery remains challenging and indications need to be clarified.

Circulating metabolic markers after surgery identify patients at risk for severe postoperative complications: a prospective cohort study in colorectal cancer.

BACKGROUND: Early detection of postoperative complications after colorectal cancer (CRC) surgery is associated with improved outcomes. The aim was to investigate early metabolomics signatures capable to detect patients at risk for severe postoperative complications after CRC surgery. MATERIALS AND METHODS: Prospective cohort study of patients undergoing CRC surgery from 2015 to 2018. Plasma samples were collected before and after surgery, and analyzed by mass spectrometry obtaining 188 metabolites and 21 ratios. Postoperative complications were registered with Clavien-Dindo Classification and Comprehensive Complication Index. RESULTS: One hundred forty-six patients were included. Surgery substantially modified metabolome and metabolic changes after surgery were quantitatively associated with the severity of postoperative complications. The strongest positive relationship with both Clavien-Dindo and Comprehensive Complication Index (ß=4.09 and 63.05, P <0.001) corresponded to kynurenine/tryptophan, against an inverse relationship with lysophosphatidylcholines (LPCs) and phosphatidylcholines (PCs). Patients with LPC18:2/PCa36:2 below the cut-off 0.084 µM/µM resulted in a sevenfold higher risk of major complications (OR=7.38, 95% CI: 2.82-21.25, P <0.001), while kynurenine/tryptophan above 0.067 µM/µM a ninefold (OR=9.35, 95% CI: 3.03-32.66, P <0.001). Hexadecanoylcarnitine below 0.093 µM displayed a 12-fold higher risk of anastomotic leakage-related complications (OR=11.99, 95% CI: 2.62-80.79, P =0.004). CONCLUSION: Surgery-induced phospholipids and amino acid dysregulation is associated with the severity of postoperative complications after CRC surgery, including anastomotic leakage-related outcomes. The authors provide quantitative insight on metabolic markers, measuring vulnerability to postoperative morbidity that might help guide early decision-making and improve surgical outcomes.

Hernias at the extraction incision after laparoscopic colon and rectal resection: Influence of incision location and use of prophylactic mesh. / 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.

Modificación del abordaje quirúrgico en tumores estromales gástricos posterior a neoadyuvancia con Imatinib / Change of surgical approach in gastrointestinal stromal tumors after neoadyuvant therapy with Imatinib

Resumen Introducción: El tratamiento de los tumores estromales gastrointestinales (GIST) de alto riesgo es quirúrgico. Su resultado podría variar al usarse neoadyuvancia. Objetivo: Evaluar si el uso de la terapia neoadyuvante con imatinib puede cambiar el abordaje quirúrgico en los tumores estromales gastrointestinales de alto riesgo. Materiales y Métodos: Se realizó un análisis retrospectivo en el Hospital Clínic de Barcelona entre enero de 2002 y mayo de 2016. Resultados: Se obtuvo un total de 8 pacientes. La edad media fue 66,1 ± 13,3 años. La ubicación del tumor fue de 37,5% (3) en el tercio superior, el 50% (4) en el tercio medio y el 12,5% (1) en el tercio inferior. Debido a la clasificación de riesgo alto, la ubicación y/o la necesidad de resecciones multiviscerales, se indicó, previa evaluación comité oncológico, realizar terapia neoadyuvante. La mediana de tiempo de neoadyuvancia fue de 30 semanas. En el 100% (8) de los casos se logró un cambio de enfoque quirúrgico después de la utilización de imatinib. En todos los casos se realizó un resección local (7 laparoscópica y 1 endolaparoscópica) con márgenes negativos La biopsia posoperatoria mostró un promedio de 51,2% de reducción del tamaño tumoral inicial, lo que resultó en una diferencia estadística (p < 0,01) con el tamaño inicial de las lesiones. Durante el seguimiento, tanto la sobrevida relacionada al tumor como la global, fue de un 100%. Conclusión: La terapia neoadyuvante podría cambiar el abordaje quirúrgico de los pacientes con GIST gástrico de riesgo intermedio o alto mediante la reducción del tamaño tumoral, permitiendo realizar cirugías más económicas y logrando resultados oncológicos adecuados.

Introduction: The treatment of high-risk gastrointestinal stromal tumors (GIST) is surgical. Results may change when using neoadjuvant. Objetive: To evaluated if the use of neoadjuvant therapy with imatinib can change the surgical approach in high risk gastrointestinal stromal tumors (GIST). Materials and Methods: A retrospective analysis was performed from a prospective collected database in Hospital Clinic of Barcelona between January 2002 and May 2016. Results: A total of 8 patients were analyzed with a mean age of 66.1 ± 13.3 years. The tumor location was upper third 37.5% (3) cases, 50% (4) in the middle third and 12.5% (1) in lower third. Because of high risk classification, location and the need of multivisceral resections, neoadjuvant therapy was indicated. The median time of neoadjuvant therapy was 30 weeks. In 87.5% (7) cases a change of surgical approach was achieved after the use of imatinib. In 100% of our series laparoscopic wedge resection was performed achieving negative margins of resection. The postoperative biopsy showed 51.2% of reduction of initial tumor size, resulting in statistical difference (p < 0.01). All patients are alive and 100% of tumor related survival was achieved. Conclusion: Neoadjuvant therapy maybe can change the surgical approach of patients with high-intermediate risk gastric GIST by reducing tumor size. This response also eventually can achieve optimal oncological outcome.

Multidisciplinary approach to hemodialysis graft dysfunction and thrombosis.

PURPOSE: Top analize the clinic results of the implantation of a multidisciplinary protocol to maintain permeability of the arteriovenous hemodialysis grafts (AVG). METHOD: Prospective recording of all interventions (radiological and surgical) on AVG dysfunction in the 1999-2007 period. The AVG stenosis were always treated by percutaneous angioplasty (PA) except stenosis recurrence in less than three months or persistence after PA. The AVG thromboses were always treated by surgical thrombectomy plus PTFE bridge if necessary. Complications, primary and secondary AVG patency were reviewed. RESULTS: Ninety six dysfunction AVG were collected for study. All of them were 6x40 mm standard wall PTFE (Gore-Tex®). Thirty six of them were humero-basilic antebraquial loop and sixty were humero-axillary upper arm curve configuration. During the study, 52 PTFE bridges, 109 surgical thrombectomies, 131 PA, and 15 stents were needed to maintain FAVP permeability. Primay patency was 73.68%, 60.21% and 37.52% at one, two and three years respectively. Secondary patency was 89.49%, 84.07% and 66.84% at one, two and three years respectively. We avoid a central venous catheter (CVC) in the 80% of intervention for thrombosis dysfunction. No surgical or radiological related deaths occurred. Median hospital admission related with AVG thrombosis was 0.03/patient/year. CONCLUSION: The application of a combined protocol for the treatment of AVG dysfunction and thrombosis, according to DOQI recomendations obtains good results in AVG patency in our experience.

Surgical treatment of juxta-anastomotic stenosis in radiocephalic fistula. A new proximal radiocephalic anastomosis.

INTRODUCTION: The juxta-anastomotic stenosis is the most frequent cause of dysfunction in radiocephalic fistulas for haemodialysis. This adversity can cause low flow or thrombosis. The appropriate treatment of these lesions is under debate. METHOD: A prospective study was performed from 1998 to 2009. All dysfunctional radiocephalic fistulas due to juxta-anastomotic stenosis were included (n=96). The diagnosis was made by fistulografy in low flow cases and clinical evidence in cases of thrombosis. The repair was performed using a new proximal radiocephalic anastomosis in all cases. Patency following surgical intervention was estimated with the Kaplan-Meier method. RESULTS: A total of 96 proximal radiocephalic anastomoses were performed during the study period. Mean surveillance time was 57.27 months (95% CI: 47.53-67.02). Sixty-six patients were male, and the mean age was 67 years. Scheduled surgery was performed in 70.5% of cases and 29.5% were emergency procedures, 92% of which were ambulatory. Technical success was achieved in 100% without any complications. Mean primary patency at 1, 2, 3, 4, and 5 years was 89.4%, 75%, 70.4%, 65%, and 56%, respectively. Additional procedures (n=16) were required in 14 cases (twelve new proximal anastomoses and four cases of arteriovenous graft placement), resulting in mean secondary patency at 1, 2, 3, 4, and 5 years of 93.7%, 92.1%, 89.6%, 87%, and 82.6%, respectively. Mean secondary patency of initial dysfunctional radiocephalic fistulas at 1, 2, 3, 4, and 5 years was 95%, 95%, 93.2%, 89.1%, and 86.6%, respectively. CONCLUSIONS: In our experience the proximal radiocephalic anastomosis can significantly extend fistula functionality in patients with juxta-anastomotic stenosis.