"Long-term oncologic outcomes and risk factors for distant recurrence after pathologic complete response following neoadjuvant treatment for locally advanced rectal cancer. A nationwide, multicentre study".

BACKGROUND: Pathologic complete response (pCR) after multimodal treatment for locally advanced rectal cancer (LARC) is used as surrogate marker of success as it is assumed to correlate with improved oncologic outcome. However, long-term oncologic data are scarce. METHODS: This retrospective, multicentre study updated the oncologic follow-up of prospectively collected data from the Spanish Rectal Cancer Project database. pCR was described as no evidence of tumour cells in the specimen. Endpoints were distant metastases-free survival (DMFS) and overall survival (OS). Multivariate regression analyses were run to identify factors associated with survival. RESULTS: Overall, 32 different hospitals were involved, providing data on 815 patients with pCR. At a median follow-up of 73.4 (IQR 57.7-99.5) months, distant metastases occurred in 6.4% of patients. Abdominoperineal excision (APE) (HR 2.2, 95%CI 1.2-4.1, p = 0.008) and elevated CEA levels (HR = 1.9, 95% CI 1.0-3.7, p = 0.049) were independent risk factors for distant recurrence. Age (years) (HR 1.1; 95%-CI 1.05-41.09; p < 0.001) and ASA III-IV (HR = 2.0; 95%-CI 1.4-2.9; p < 0.001), were the only factors associated with OS. The estimated 12, 36 and 60-months DMFS rates were 96.9%, 91.3%, and 86.8%. The estimated 12, 36 and 60-months OS rates were 99.1%, 94.9% and 89.3%. CONCLUSIONS: The incidence of metachronous distant metastases is low after pCR, with high rates of both DMFS and OS. The oncologic prognosis in LARC patients that achieve pCR after neoadjuvant chemo-radiotherapy is excellent in the long term.

Hemoperitoneo secundario a lesión esplénica tras colonoscopia diagnóstica. Una complicación infrecuente

Introducción: La colonoscopia es una herramienta básica en el estudio de patologías del área colorrectal, así como uno de los pilares del screening del cáncer de colon y recto. Sin embargo, no es un procedimiento exento de riesgos, algunos de ellos con elevada morbimortalidad. Caso Clínico: Varón de 55 años con enolismo crónico y hepatopatía por Virus Hepatitis C y Enfermedad Pulmonar Obstructiva Crónica. En estudio por diarrea se solicita una ecografía de abdomen donde, como único hallazgo, se muestra una lesión de 7 mm a nivel de páncreas y una colonoscopia con intención diagnóstica que no muestra alteraciones significativas. Con la sospecha de que la lesión pancreática pudiese ser la causa del cuadro diarreico, se realiza un escáner abdominal donde se muestra una colección subcapsular a nivel esplénico de 11 × 3 cm compatible con hematoma sin signos de sangrado activo. Dada la estabilidad hemodinámica, se inicia manejo conservador, con empeoramiento del dolor abdominal e hipotensión en las siguientes 12 h. Se repite prueba de imagen objetivando aumento de hematoma esplénico y líquido libre intraabdominal. Se indica cirugía urgente donde se evidencia hemoperitoneo secundario a lesión esplénica que obliga a realizar esplenectomía. Conclusión: La presencia de una posible lesión esplénica yatrogénica se debe tener en cuenta en el diagnóstico diferencial en un paciente con dolor abdominal de inicio agudo y anemización o alteración del estado hemodinámico dentro de las primeras 24-48 h tras la realización de una colonoscopia.

Introduction: Colonoscopy is a basic tool in the study of pathology of the colorectal area, as well as one of the pillars of colon and rectal cancer screening. However, it is not a risk-free procedure, some of them with high morbimortality. Case Report: 55-year-old male with chronic alcoholism and hepatopathy due to HCV, COPD. During a study for diarrhea, an ultrasound of the abdomen revealed a 7 mm pancreas tumor, and a diagnostic colonoscopy showed no significant alterations. With the suspicion that the pancreatic lesion could be the cause of the diarrhea, an abdominal scan was performed showing a subcapsular collection at the splenic level of 11 × 3 cm compatible with hematoma without signs of active bleeding. Due to the hemodynamic stability, conservative management was decided, with worsening abdominal pain and hypotension in the following 12 hours. A new imaging test showed an enlarged splenic hematoma and free abdominal fluid suggestive of hemoperitoneum. Urgent surgery found hemoperitoneum secondary to splenic lesion and splenectomy was required. Conclusion: The presence of a possible iatrogenic splenic lesion should be considered in the differential diagnosis in a patient with acute onset abdominal pain and anemia or hemodynamic status alteration within the first 24-48 hours after colonoscopy.

Is prophylactic mesh closure effective to decrease the incidence of incisional hernia after laparotomy in colorectal surgery?

BACKGROUND: few studies have studied prophylactic mesh closure after laparotomy for colorectal surgery. METHODS: a retrospective cohort study was performed to compare patients with and without prophylactic mesh closure after open colorectal surgery. RESULTS: 309 patients were included from January 2014 to December 2016. Prophylactic mesh closure was performed in 98 patients (31.7%). After a mean follow-up of 21.7 months, incisional hernia was developed in 9 and 54 patients in the group with and without mesh respectively (9.2% vs. 25.7%, OR = 0.3, p = 0.001). In the multivariate Cox model prophylactic mesh closure was associated with a protective effect on incisional hernia development with a Hazard Ratio of 0.46 (p = 0.033). Surgical site infection was more frequent in the mesh group (19.4% vs. 9.5%, OR = 2.3, p = 0.015). CONCLUSIONS: prophylactic mesh closure is effective to decrease the incidence of incisional hernia after colorectal surgery.

NT3/TrkC Pathway Modulates the Expression of UCP-1 and Adipocyte Size in Human and Rodent Adipose Tissue.

Neurotrophin-3 (NT3), through activation of its tropomyosin-related kinase receptor C (TrkC), modulates neuronal survival and neural stem cell differentiation. It is widely distributed in peripheral tissues (especially vessels and pancreas) and this ubiquitous pattern suggests a role for NT3, outside the nervous system and related to metabolic functions. The presence of the NT3/TrkC pathway in the adipose tissue (AT) has never been investigated. Present work studies in human and murine adipose tissue (AT) the presence of elements of the NT3/TrkC pathway and its role on lipolysis and adipocyte differentiation. qRT-PCR and immunoblot indicate that NT3 (encoded by NTF3) was present in human retroperitoneal AT and decreases with age. NT3 was also present in rat isolated adipocytes and retroperitoneal, interscapular, perivascular, and perirenal AT. Histological analysis evidences that NT3 was mainly present in vessels irrigating AT close associated to sympathetic fibers. Similar mRNA levels of TrkC (encoded by NTRK3) and ß-adrenoceptors were found in all ATs assayed and in isolated adipocytes. NT3, through TrkC activation, exert a mild effect in lipolysis. Addition of NT3 during the differentiation process of human pre-adipocytes resulted in smaller adipocytes and increased uncoupling protein-1 (UCP-1) without changes in ß-adrenoceptors. Similarly, transgenic mice with reduced expression of NT3 (Ntf3 knock-in lacZ reporter mice) or lacking endothelial NT3 expression (Ntf3flox1/flox2;Tie2-Cre+/0) displayed enlarged white and brown adipocytes and lower UCP-1 expression. Conclusions: NT3, mainly released by blood vessels, activates TrkC and regulates adipocyte differentiation and browning. Disruption of NT3/TrkC signaling conducts to hypertrophied white and brown adipocytes with reduced expression of the thermogenesis marker UCP-1.

Extraction-site incisional hernia after laparoscopic colorectal surgery: should we carry out a study about prophylactic mesh closure?

BACKGROUND: Prophylactic mesh closure has only scarcely been studied to avoid extraction-site incisional hernia after laparoscopic colorectal surgery. The aim was to analyze extraction-site incisional hernia incidence after laparoscopic colorectal surgery to assess if prophylactic mesh closure should be studied. METHODS: A retrospective analytic cohort study was conducted in patients who had undergone laparoscopic colorectal surgery with an extraction-site incision. Extraction-site incisional hernia was diagnosed during clinical examination or imaging. Risk factors for extraction-site incisional hernia were analyzed. RESULTS: Two hundred and twenty-five patients were included. More than 80% of the patients had a malignant disease. Ninety-two patients (40.9%) underwent right colectomy. Midline extraction-site incision was used in 86 (38.2%) patients. After a mean follow-up of 2.4 years, 39 (17.3%) patients developed an extraction-site incisional hernia. Midline extraction-site incision was associated with incisional hernia when compared to transverse and Pfannenstiel incision (39.5% vs. 3.6%, OR 17.5, p < 0.001). Surgery to repair an extraction-site incisional hernia was also more frequent in the group of patients with a midline incision (10.5% vs. 1.4%, OR 8.0, p = 0.002). In the multivariate analysis, incisional hernia was associated with body mass index, high blood pressure, and midline incision. CONCLUSIONS: Extraction-site incisional hernia was mainly related to midline incisions; therefore, midline incision should be avoided whenever possible. Studying prophylactic mesh closure for Pfannesnstiel or transverse incisions is needless, as these incisions have a low incisional hernia risk.

Calcium oscillations in human mesenteric vascular smooth muscle.

Phenylephrine (PE)-induced oscillatory fluctuations in intracellular Ca(2+) concentration ([Ca(2+)]i) of vascular smooth muscle have been observed in many blood vessels isolated from a wide variety of mammals. Paradoxically, until recently similar observations in humans have proven elusive. In this study, we report for the first time observations of adrenergically-stimulated [Ca(2+)]i oscillations in human mesenteric artery smooth muscle. In arterial segments preloaded with Fluo-4 AM and mounted on a myograph on the stage of a confocal microscope, we observed PE-induced oscillations in [Ca(2+)]i, which initiated and maintained vasoconstriction. These oscillations present some variability, possibly due to compromised health of the tissue. This view is corroborated by our ultrastructural analysis of the cells, in which we found only (5 ± 2)% plasma membrane-sarcoplasmic reticulum apposition, markedly less than measured in healthy tissue from laboratory animals. We also partially characterized the oscillations by using the inhibitory drugs 2-aminoethoxydiphenyl borate (2-APB), cyclopiazonic acid (CPA) and nifedipine. After PE contraction, all drugs provoked relaxation of the vessel segments, sometimes only partial, and reduced or inhibited oscillations, except CPA, which rarely caused relaxation. These preliminary results point to a potential involvement of the sarcoplasmic reticulum Ca(2+) and inositol 1,4,5-trisphosphate receptor (IP3R) in the maintenance of the Ca(2+) oscillations observed in human blood vessels.

Age-dependent defective TGF-beta1 signaling in patients undergoing coronary artery bypass grafting.

BACKGROUND: Transforming growth factor beta (TGF-ß1) is a pleiotropic cytokine, which is deregulated in atherosclerosis; however the role of age in this process is unknown. We aimed to assess whether TGF-ß1 signaling is affected by age. METHODS: Vascular smooth muscle cells (VSMC) were obtained from patients undergoing abdominal surgery. Levels of TGF-ß1 were measured by ELISA in sera from 169 patients undergoing coronary artery bypass grafting (CABG). The p27 expression was determined by Western blot from internal mammary arteries (IMA) obtained from CABG patients (n=13). In VSMC from these patients undergoing abdominal surgery, secretion of TGF-ß1 was determined by ELISA of cell-conditioned media. RESULTS: In VSMC from aged patients we observed a lower TGF-ß1 secretion, measured as TGF-ß1 concentration in cell conditioned medium (p<0.001). This effect was correlated to an age-dependent decrease of p27 expression in IMA from aged CABG patients. In a similar manner, there was an age-dependent decrease of serum TGF-ß1 levels in CABG patients (p=0.0195). CONCLUSIONS: VSMC from aged patients showed a higher degree of cellular senescence and it was associated to a lower TGF-ß1 secretion and signaling.

[Results of applying a fast-track protocol in a colorectal surgery unit: comparative study]. / Resultados de la implantación de un protocolo de fast-track en una unidad de cirugía colorrectal: estudio comparativo.

OBJECTIVE: To implement a fast-track (FT) protocol in a colorectal surgery unit, checking its safety when applied to patients subjected to elective colorectal surgery, by evaluating the differences in morbidity and hospital stay compared to a control group with traditional care. We also analyse the functional recovery of the FT group. MATERIAL AND METHOD: A prospective cohort study with non-concurrent control, was conducted on a group of 108 patients operated on for colorectal cancer between 2008 and 2009, to which the FT protocol was applied, and a control group (CG) of 147 patients subjected to surgery between 2005 and 2007 with similar characteristics, with traditional postoperative care. RESULTS: The demographic characteristics, anaesthetic risk, and the surgical procedures performed were similar, with a higher number of patients with laparoscopic approach in the FT group. The compliance with the items in our FT protocol was high (72.2-92.6%). Complications were observed in 77 patients (52%) in the GC compared to 30 (27.8%) in the FT group (P<.001), mainly due to the decrease in surgical wound infection (P<.001). Mortality and the number of readmissions were less in the FT group, with no statistically significant differences. The median hospital stay was 14 days in the CG and 8 in the FT group (P<.001). CONCLUSIONS: The applying of an FT program in colorectal surgery is safe, leading to a significant decrease in morbidity and hospital stay, without increasing the number of readmissions.

A comparative study of alpha-adrenergic receptor mediated Ca(2+) signals and contraction in intact human and mouse vascular smooth muscle.

In many vascular smooth muscle cells, physiological and pharmacological agonists initiate oscillatory fluctuations in intracellular Ca(2+) to initiate and maintain vasoconstriction. These oscillations are supported by the underlying cellular ultrastructure, particularly the close apposition between the plasma membrane (PM) and superficial sarcoplasmic reticulum (SR), the so-called PM-SR junctions, which are important for SR Ca(2+) refilling. We hypothesize that the disappearance of PM-SR junctions during aging and/or disease is directly related to the disappearance of agonist-induced Ca(2+) oscillations. We compared phenylephrine-mediated Ca(2+) signals and contraction in human and murine smooth muscle cells in small mesenteric arteries and also employed electron microscopy to examine the cytoplasmic distribution of the SR. Phenylephrine elicited tonic contractions in both types of vessels, asynchronous Ca(2+) oscillations in the mouse mesenteric smooth muscle cells, but only single transient Ca(2+) signals in the human mesenteric smooth muscle cells. While nifedipine inhibited 90% of the phenylephrine-induced tonic contraction in mouse mesenteric arteries, it only slightly attenuated tonic contraction in human mesenteric arteries, although the nifedipine-resistant component was abolished by the Rho-kinase blocker 1-(5-Isoquinolinylsulfonyl)homopiperazine dihydrochloride (HA-1077). Furthermore, superficial SR was found to be abundant in the mouse vessels and many PM-SR junctions were observed, but the smooth muscle of human mesenteric arteries had far less peripheral SR and was almost devoid of PM-SR junctions. As PM-SR junctions are essential for the maintenance of Ca(2+) oscillations, the change in Ca(2+) signalling pattern in the relatively old human patients was due to impaired SR refilling.

A new paradigm in respiratory hygiene: modulating respiratory secretions to contain cough bioaerosol without affecting mucus clearance.

BACKGROUND: Several strategies and devices have been designed to protect health care providers from acquiring transmissible respiratory diseases while providing care. In modulating the physical characteristics of the respiratory secretions to minimize the aerosolization that facilitates transmission of airborne diseases, a fundamental premise is that the prototype drugs have no adverse effect on the first line of respiratory defense, clearance of mucus by ciliary action. METHODS: To assess and demonstrate the primary mechanism of our mucomodulators (XLs), we have built our evidence moving from basic laboratory studies to an ex-vivo model and then to an in-vivo large animal model. We exposed anesthetized dogs without hypersecretion to different dose concentrations of aerosolized XL "B", XL "D" and XL "S". We assessed: cardio-respiratory pattern, tracheal mucus clearance, airway patency, and mucus viscoelastic changes. RESULTS: Exposure of frog palate mucus to XLs did not affect the clearance of mucus by ciliary action. Dogs maintained normal cardio-respiratory pattern with XL administration. Tracheal mucociliary clearance in anesthetized dogs indicated a sustained 40% mean increase. Tracheal mucus showed increased filance, and there was no mucus retention in the airways. CONCLUSION: The ex-vivo frog palate and the in-vivo mammalian models used in this study, appear to be appropriate and complement each other to better assess the effects that our mucomodulators exert on the mucociliary clearance defence mechanism. The physiological function of the mucociliary apparatus was not negatively affected in any of the two epithelial models. Airway mucus crosslinked by mucomodulators is better cleared from an intact airway and normally functioning respiratory system, either due to enhanced interaction with cilia or airflow-dependent mechanisms. Data obtained in this study allow us to assure that we have complied with the fundamental requirement criteria established in the initial phase of developing the concept of mucomodulation: Can we modulate the physical characteristics of the respiratory secretions to reduce aerosolization without affecting normal mucociliary clearance function, or even better improving it?