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1.
Nature ; 593(7860): 591-596, 2021 05.
Article in English | MEDLINE | ID: mdl-33953402

ABSTRACT

Cell extrusion is a mechanism of cell elimination that is used by organisms as diverse as sponges, nematodes, insects and mammals1-3. During extrusion, a cell detaches from a layer of surrounding cells while maintaining the continuity of that layer4. Vertebrate epithelial tissues primarily eliminate cells by extrusion, and the dysregulation of cell extrusion has been linked to epithelial diseases, including cancer1,5. The mechanisms that drive cell extrusion remain incompletely understood. Here, to analyse cell extrusion by Caenorhabditis elegans embryos3, we conducted a genome-wide RNA interference screen, identified multiple cell-cycle genes with S-phase-specific function, and performed live-imaging experiments to establish how those genes control extrusion. Extruding cells experience replication stress during S phase and activate a replication-stress response via homologues of ATR and CHK1. Preventing S-phase entry, inhibiting the replication-stress response, or allowing completion of the cell cycle blocked cell extrusion. Hydroxyurea-induced replication stress6,7 triggered ATR-CHK1- and p53-dependent cell extrusion from a mammalian epithelial monolayer. We conclude that cell extrusion induced by replication stress is conserved among animals and propose that this extrusion process is a primordial mechanism of cell elimination with a tumour-suppressive function in mammals.


Subject(s)
Caenorhabditis elegans Proteins/genetics , Cell Cycle Proteins/genetics , DNA Replication , Regulated Cell Death , S Phase , Animals , Ataxia Telangiectasia Mutated Proteins , Caenorhabditis elegans/cytology , Caenorhabditis elegans/genetics , Cell Cycle Checkpoints , Checkpoint Kinase 1 , DNA Damage , Dogs , Embryo, Nonmammalian , Gene Expression Regulation, Developmental , Madin Darby Canine Kidney Cells , RNA Interference
2.
Br J Surg ; 111(2)2024 Jan 31.
Article in English | MEDLINE | ID: mdl-38381934

ABSTRACT

BACKGROUND: Neoadjuvant chemotherapy is increasingly used to treat locally advanced (T3-4 Nx-2 M0) colon cancer due to its potential advantages over the standard approach of upfront surgery. The primary objective of this systematic review and meta-analysis was to analyse data from comparative studies to assess the impact of neoadjuvant chemotherapy on oncological outcomes. METHODS: A systematic review was conducted by searching the MEDLINE and Scopus databases. The search encompassed RCTs, propensity score-matched studies, and controlled prospective studies published up to 1 April 2023. As a primary objective, overall survival and disease-free survival were compared. As a secondary objective, perioperative morbidity, mortality, and complete resection were compared using the DerSimonian and Laird models. RESULTS: A total of seven studies comprising a total of 2120 patients were included. Neoadjuvant chemotherapy was associated with a reduction in the hazard of recurrence (HR 0.73, 95% c.i. 0.59 to 0.90; P = 0.003) and death (HR 0.67, 95% c.i. 0.54 to 0.83; P < 0.001) compared with upfront surgery. Additionally, neoadjuvant chemotherapy was significantly associated with higher 5-year overall survival (79.9% versus 72.6%; P < 0.001) and disease-free survival (73.1% versus 64.5%; P = 0.028) rates. No significant differences were observed in perioperative mortality (OR 0.97, 95% c.i. 0.28 to 3.33), overall complications (OR 0.95, 95% c.i. 0.77 to 1.16), or anastomotic leakage/intra-abdominal abscess (OR 0.88, 95% c.i. 0.60 to 1.29). However, neoadjuvant chemotherapy was associated with a lower risk of incomplete resection (OR 0.70, 95% c.i. 0.49 to 0.99). CONCLUSION: Neoadjuvant chemotherapy is associated with a reduced hazard of recurrence and death, as well as improved overall survival and disease-free survival rates, compared with upfront surgery in patients with locally advanced colon cancer.


Colon cancer is a common medical condition, the established treatment for which involves surgical resection followed by chemotherapy. However, a contemporary shift has led to the investigation of an alternative treatment sequence known as neoadjuvant chemotherapy, wherein chemotherapy precedes the surgery. This study critically assesses the efficacy of neoadjuvant chemotherapy compared with the standard treatment approach of surgery followed by chemotherapy. A systematic review of medical databases was undertaken to identify pertinent research publications on this subject matter. In total, seven studies encompassing data from 2120 patients were included in the analysis. Employing a meta-analysis methodology to synthesize the collective data from these studies, it was revealed that neoadjuvant chemotherapy was linked to higher rates of 5-year overall survival and disease-free survival, alongside a diminished hazard of both recurrence and death. Furthermore, no discernible differences in surgical complications or perioperative mortality were evident across the compared approaches.


Subject(s)
Colonic Neoplasms , Neoadjuvant Therapy , Humans , Prospective Studies , Chemotherapy, Adjuvant , Disease-Free Survival , Colonic Neoplasms/drug therapy , Colonic Neoplasms/surgery
3.
Colorectal Dis ; 26(4): 745-753, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38362850

ABSTRACT

BACKGROUND: Colon cancer (CC) is a public health concern with increasing incidence in younger populations. Treatment for locally advanced CC (LACC) involves oncological surgery and adjuvant chemotherapy (AC) to reduce recurrence and improve overall survival (OS). Neoadjuvant chemotherapy (NAC) is a novel approach for the treatment of LACC, and research is underway to explore its potential benefit in terms of survival. This trial will assess the efficacy of NAC in LACC. METHODS: This is a multicentre randomised, parallel-group, open label controlled clinical trial. Participants will be selected based on homogenous inclusion criteria and randomly assigned to two treatment groups: NAC, surgery, and AC or surgery followed by AC. The primary aim of this study is to evaluate the 2-year progression-free survival (PFS), with secondary outcomes including 5-year PFS, 2- and 5-year OS, toxicity, radiological and pathological response, morbidity, and mortality. DISCUSSION: The results of this study will determine whether NAC induces a clinical and histological tumour response in patients with CCLA and if this treatment sequence improves survival without increasing morbidity and mortality. REGISTRATION NUMBER: NCT04188158.


Subject(s)
Colonic Neoplasms , Neoadjuvant Therapy , Adult , Aged , Female , Humans , Male , Middle Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Chemotherapy, Adjuvant/methods , Colectomy/methods , Colonic Neoplasms/pathology , Colonic Neoplasms/mortality , Colonic Neoplasms/drug therapy , Colonic Neoplasms/therapy , Colonic Neoplasms/surgery , Neoadjuvant Therapy/methods , Progression-Free Survival , Randomized Controlled Trials as Topic , Treatment Outcome , Multicenter Studies as Topic
4.
Tech Coloproctol ; 27(12): 1345-1350, 2023 12.
Article in English | MEDLINE | ID: mdl-37770748

ABSTRACT

PURPOSE: Rectal cancer surgery presents challenges in achieving good oncological results and preserving functional outcomes. Different surgical approaches, including open, laparoscopic, robotic and transanal techniques, have been employed, but there is a lack of consensus on the optimal approach, particularly in terms of functional results. This study aims to assess bowel function and to compare outcomes of patients that had undergone surgery for mid-low rectal cancer across different surgical approaches. METHOD: This is an international, multicentre, prospective cohort study. Inclusion criteria are patients diagnosed with rectal cancer below the peritoneal reflection, eligible for different surgical approaches for total mesorectal excision (TME). Data will be collected using validated questionnaires assessing bowel, sexual and urinary function, and quality of life (QOL). Secondary outcomes include short-term postoperative results. Data will be collected at baseline and 6, 12 and 24 months after index surgery or stoma reversal surgery. CONCLUSION: This study will provide insights into the impact of different approaches for TME on bowel, sexual and urinary function, and overall QOL of patients undergoing rectal cancer surgery. The findings will provide important information to optimise the surgical strategy and to improve patient care in this population. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04936581 (registered 23 June 2021).


Subject(s)
Laparoscopy , Rectal Neoplasms , Humans , Quality of Life , Prospective Studies , Rectum/surgery , Rectal Neoplasms/surgery , Laparoscopy/methods , Patient Reported Outcome Measures , Postoperative Complications/etiology , Postoperative Complications/surgery , Treatment Outcome , Multicenter Studies as Topic
5.
Int J Mol Sci ; 24(4)2023 Feb 09.
Article in English | MEDLINE | ID: mdl-36834938

ABSTRACT

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.


Subject(s)
Colorectal Neoplasms , Early Detection of Cancer , Telomere , Humans , Middle Aged , Colorectal Neoplasms/diagnosis , Colorectal Neoplasms/genetics , Incidence , Telomere/genetics , Telomere/metabolism , Biomarkers, Tumor , Early Detection of Cancer/methods
6.
Colorectal Dis ; 24(5): 659-663, 2022 05.
Article in English | MEDLINE | ID: mdl-35038374

ABSTRACT

AIM: The aim was to describe the range of possibilities and our group's clinical outcomes when performing different types of anastomosis during transanal total mesorectal excision (taTME). METHOD: A retrospective analysis was performed based on four taTME series from 2016 to 2021. Inclusion criteria were patients with rectal cancer in whom a sphincter-saving low anterior resection by taTME was performed. Four different techniques were employed for the anastomosis construction: (A) abdominal view, (B) transanal view, (C) hand-sewn coloanal anastomosis and (D) pull-through. Intra-operative and postoperative data were collected and compared. RESULTS: A total of 161 patients were included. Tumour height was lower in groups C and D (4 [3-5] vs. 7 [6-8] group A vs. 6 [5-7] group B, P = 0.000), requiring a hand-sewn anastomosis. A transanal extraction of the specimen was more commonly performed in groups C and D (over 60% vs. 30% in groups A and B, P = 0.000). The rate of temporary stoma was similar between groups A, B and C (ranging from 84% to 98%) but was significantly lower in group D (P = 0.000). The overall rate of complications was similar between groups; however, group D had longer length of stay (15 days vs. 5-6 in groups A, B and C, P = 0.026). CONCLUSION: Every type of anastomosis construction after a taTME procedure seems to be safe and feasible and should be chosen based on surgeon's experience, tumour height and the length of the rectal cuff after the rectal transection. Colorectal surgeons should be familiar with these techniques in order to choose the one that benefits each patient the most.


Subject(s)
Laparoscopy , Rectal Neoplasms , Transanal Endoscopic Surgery , Anastomosis, Surgical/methods , Humans , Laparoscopy/methods , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Postoperative Complications/surgery , Rectal Neoplasms/surgery , Rectum/surgery , Retrospective Studies , Transanal Endoscopic Surgery/methods
7.
Tech Coloproctol ; 26(9): 745-753, 2022 09.
Article in English | MEDLINE | ID: mdl-35637355

ABSTRACT

BACKGROUND: The present case-series describes the first full-robotic colorectal resections performed with the new CMR Versius platform (Cambridge Medical Robotics Surgical, 1 Evolution Business Park, Cambridge, United Kingdom) by an experienced robotic surgeon. METHODS: In a period between July 2020 and December 2020, patients aged 18 years or older, who were diagnosed with colorectal cancer and were fit for minimally invasive surgery, underwent robotic colorectal resection with CMR Versius robotic platform at "Casa di Cura Cobellis" in Vallo della Lucania,Salerno, Italy. Three right colectomies, 2 sigmoid colectomies and 1 anterior rectal resection were performed. All the procedures were planned as fully robotic. Surgical data were retrospectively reviewed from a prospectively collected database. RESULTS: Four patients were male and 2 patients were female with a median (range) age of 66 (47-72) years. One covering ileostomy was created. Full robotic splenic flexure mobilization was performed. No additional laparoscopic gestures or procedures were performed in this series except for clipping and stapling which were performed by the assistant surgeon due to the absence of robotic dedicated instruments. Two ileocolic anastomoses, planned as robotic-sewn, were performed extracorporeally. One Clavien-Dindo II complication occurred due to a postoperative blood transfusion. Median total operative time was 160 (145-294) min for right colectomies, 246 (191-300) min for sigmoid colectomies and 250 min for the anterior rectal resection. CONCLUSIONS: The present series confirms the feasibility of full-robotic colorectal resections while highlighting the strengths and the limitations of the CMR Versius platform in colorectal surgery. New devices will need more clinical development to be comparable to the current standard.


Subject(s)
Colorectal Neoplasms , Colorectal Surgery , Laparoscopy , Robotic Surgical Procedures , Colectomy/methods , Colorectal Neoplasms/surgery , Female , Humans , Laparoscopy/methods , Male , Retrospective Studies , Robotic Surgical Procedures/methods
8.
Surg Endosc ; 35(4): 1808-1819, 2021 04.
Article in English | MEDLINE | ID: mdl-32333158

ABSTRACT

BACKGROUND: There is no consensus regarding the gold standard technique for rectal cancer as Total Mesorectal Excision (TME) may be safely performed either by open or minimally invasive surgery. The laparoscopic approach, however, may carry technical difficulties. For this reason, a novel technique has emerged in the last decade combining a dual laparoscopic dissection (abdominal and transanal) to perform the TME technique (TaTME). When focusing on oncological outcomes, there is a lack of literature regarding mid-long term results. The aim of this study is to evaluate the mid-term oncological impact of TaTME for treating rectal cancer. METHODS: A prospective multicentre study was performed in four tertiary centres including consecutive patients who underwent TaTME for mid-low rectal cancer by the same group of experienced surgeons. The analysed data included pathological results on the quality of TME and mid-term oncological outcomes. RESULTS: In total, 173 patients were included throughout a study period of 6 years. Our series included 70% males and 68% of patients with neoadjuvant treatments. The median follow-up was 23 [15-37.5] months. Regarding pathological results, a complete TME was achieved in 72.8%, while circumferential and distal margins were affected in 1.4 and 1.1%, respectively. Five patients developed local recurrences (3%) and 8.1% presented distant disease during the follow-up. The 2-year disease-free survival and the overall survival rates were 88% and 95%, respectively. CONCLUSIONS: There is currently a lack of evidence in the literature regarding TaTME and oncological outcomes with no data available from randomized clinical trials. In the meantime, the reported results from different multicentre series are controversial. This study showed positive mid-term outcomes at 2 years of follow-up and supported notable oncological outcomes with TaTME. However, it must be emphasized that previous experience in minimally invasive and transanal surgeries is essential for surgeons before intending to perform TaTME.


Subject(s)
Rectal Neoplasms/surgery , Transanal Endoscopic Surgery/adverse effects , Aged , Disease-Free Survival , Female , Humans , Laparoscopy , Male , Margins of Excision , Middle Aged , Neoadjuvant Therapy , Neoplasm Staging , Postoperative Care , Prospective Studies , Rectal Neoplasms/radiotherapy , Treatment Outcome
9.
Proc Natl Acad Sci U S A ; 115(8): 1925-1930, 2018 02 20.
Article in English | MEDLINE | ID: mdl-29432180

ABSTRACT

Actin polymerization and assembly into stress fibers (SFs) is central to many cellular processes. However, how SFs form in response to the mechanical interaction of cells with their environment is not fully understood. Here we have identified Piezo2 mechanosensitive cationic channel as a transducer of environmental physical cues into mechanobiological responses. Piezo2 is needed by brain metastatic cells from breast cancer (MDA-MB-231-BrM2) to probe their physical environment as they anchor and pull on their surroundings or when confronted with confined migration through narrow pores. Piezo2-mediated Ca2+ influx activates RhoA to control the formation and orientation of SFs and focal adhesions (FAs). A possible mechanism for the Piezo2-mediated activation of RhoA involves the recruitment of the Fyn kinase to the cell leading edge as well as calpain activation. Knockdown of Piezo2 in BrM2 cells alters SFs, FAs, and nuclear translocation of YAP; a phenotype rescued by overexpression of dominant-positive RhoA or its downstream effector, mDia1. Consequently, hallmarks of cancer invasion and metastasis related to RhoA, actin cytoskeleton, and/or force transmission, such as migration, extracellular matrix degradation, and Serpin B2 secretion, were reduced in cells lacking Piezo2.


Subject(s)
Actin Cytoskeleton/metabolism , Ion Channels/metabolism , Mechanotransduction, Cellular/physiology , rhoA GTP-Binding Protein/metabolism , Actin Cytoskeleton/genetics , Calcium/metabolism , Cell Line, Tumor , Cell Movement , Gene Expression Regulation, Neoplastic , Gene Knockdown Techniques , HEK293 Cells , Humans , Ion Channels/genetics , rhoA GTP-Binding Protein/genetics
10.
Rev Esp Enferm Dig ; 113(2): 85-91, 2021 02.
Article in English | MEDLINE | ID: mdl-33261501

ABSTRACT

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.


Subject(s)
COVID-19 , Colorectal Neoplasms/surgery , Aged , Aged, 80 and over , Elective Surgical Procedures , Female , Humans , Male , Middle Aged , Prospective Studies , Retrospective Studies , Spain
11.
Rev Esp Enferm Dig ; 112(2): 127-132, 2020 Feb.
Article in English | MEDLINE | ID: mdl-31960699

ABSTRACT

BACKGROUND: the Enhanced Recovery After Surgery (ERAS) protocols aim to improve postoperative outcomes by obtaining a functional rehabilitation after surgery. The purpose of this study was to evaluate the impact of ERAS on the quality of life (QOL) of patients undergoing colorectal cancer surgeries. METHODS: a cohort observational study was designed of patients with colorectal cancer undergoing elective surgeries during a one-year period. Patients were included when the ERAS protocol was fully achieved for all the interventions, including the expected hospital discharge day. Patient reported outcomes (PROs) were evaluated by the EORTC QLQ-C30 and the QLQ-CR29 questionnaires on three different occasions: baseline before surgery and on postoperative days 7 and 30. RESULTS: the study included 40 patients who completed QOL evaluations with a mean age of 70 ± 11 years. There were no statistical differences between preoperative and postoperative QOL scores. By subgroups of QOL items, a significant decrease was observed in physical activity and role functioning when comparing preoperative vs postoperative status, whereas the cognitive, social and emotional functioning scales were similar or improved over time. CONCLUSIONS: in our experience, surgery under ERAS protocols did not have an impact on decreasing global QOL in patients undergoing elective colorectal cancer surgery. The use of ERAS protocols in colorectal surgery achieves a positive influence, not only by decreasing surgical-related complications but also in terms of functional recovery, by decreasing the negative effects of surgery on patient QOL.


Subject(s)
Colorectal Neoplasms , Digestive System Surgical Procedures , Enhanced Recovery After Surgery , Aged , Aged, 80 and over , Colorectal Neoplasms/surgery , Elective Surgical Procedures , Humans , Length of Stay , Middle Aged , Postoperative Complications/epidemiology , Quality of Life
12.
J Surg Res ; 244: 382-388, 2019 12.
Article in English | MEDLINE | ID: mdl-31325659

ABSTRACT

BACKGROUND: Diagnostic tests for fecal incontinence have been improved over time. This study aims to evaluate the role of Three-dimensional endoanal ultrasound (3D-EUS) and the Starck's score in the assessment and treatment of obstetric sphincter injuries. METHODS: A prospective observational study was performed including primiparous women who were evaluated at 20 wk of pregnancy and 3 mo after childbirth. Sphincter defects were classified according to the Starck's and Obstetrical Anal Sphincter Injuries classifications. Patients also completed the Fecal Incontinence Quality of Life and the Wexner questionnaires before and after childbirth. RESULTS: Sphincter defects were detected in 45% of the 56 women included, although 85% had an uneventful delivery. Most defects were found isolated to the external anal sphincter except for two cases, classified by a Starck's score >8. Fecal Incontinence Quality of Life and Wexner questionnaires showed a rate of symptomatic patients of around 46%. We observed that 30% of patients with sphincter injuries remained asymptomatic. CONCLUSIONS: The 3D-EUS is a useful test in assessing sphincter defects after childbirth. This method makes it possible to detect small sphincter defects that otherwise would have gone unnoticed, as 30% of patients with sphincter injuries were asymptomatic. In addition, both the 3D-EUS and the Starck's score were valuable in establishing an algorithm for the treatment of obstetric sphincter injuries.


Subject(s)
Anal Canal/diagnostic imaging , Anal Canal/injuries , Endosonography/methods , Fecal Incontinence/diagnostic imaging , Imaging, Three-Dimensional/methods , Obstetric Labor Complications/diagnostic imaging , Adult , Female , Humans , Pregnancy , Prospective Studies
13.
Rev Esp Enferm Dig ; 111(6): 453-459, 2019 Jun.
Article in English | MEDLINE | ID: mdl-31021166

ABSTRACT

BACKGROUND: the incidence of obstetric sphincter tears has risen to 15-30% and the prevalence of anal incontinence (AI) symptoms after childbirth may be as high as 40%. The present study evaluates the correlation between obstetric injuries detected by endoanal ultrasound (3D-EUS) and AI symptoms, as well as their impact on the quality of life (QOL) of women after childbirth. METHODS: a prospective observational study was performed of pregnant women evaluated before (baseline) and three months after childbirth to ensure the integrity of the anal sphincters and to evaluate possible injuries. The Fecal Incontinence Quality of Life (FIQL) questionnaire and the Cleveland Clinic Score of Incontinence (Wexner) were completed before and after childbirth. The questionnaire results were correlated with an assessment of sphincter defects performed by 3D-EUS. RESULTS: a total of 56 females were included in the study. Overall, 48% developed symptoms of AI after childbirth, with a significant decrease in their FIQL compared to the initial evaluation, 3.9 (0.05) vs 3.4 (0.8), respectively (p = 0.000). In addition, 42% of the cohort presented with some kind of obstetric sphincter defect on the 3D-EUS. Instrumental assisted delivery and the sphincter defects were the only two significant factors identified via multivariate analysis that were associated with a decrease in QOL (0.4, 95% CI, 0.07-0.8). CONCLUSIONS: AI after childbirth was associated with a huge impact on QOL, especially in patients with sphincter injuries. A complete clinical evaluation, including 3D-EUS, is recommended to prevent, manage or treat AI in primiparous females.


Subject(s)
Anal Canal/diagnostic imaging , Anal Canal/injuries , Delivery, Obstetric/adverse effects , Endosonography , Fecal Incontinence/etiology , Quality of Life , Adult , Female , Humans , Imaging, Three-Dimensional , Pregnancy , Prospective Studies
14.
J Immunol ; 196(2): 738-49, 2016 Jan 15.
Article in English | MEDLINE | ID: mdl-26673139

ABSTRACT

As an organism is exposed to pathogens during very early development, specific defense mechanisms must take effect. In this study, we used a germ-free zebrafish embryo model to show that osmotic stress regulates the activation of immunity and host protection in newly hatched embryos. Mechanistically, skin keratinocytes were responsible for both sensing the hyposmolarity of the aquatic environment and mediating immune effector mechanisms. This occurred through a transient potential receptor vanilloid 4/Ca(2+)/TGF-ß-activated kinase 1/NF-κB signaling pathway. Surprisingly, the genes encoding antimicrobial effectors, which do not have the potential to cause tissue damage, are constitutively expressed during development, independently of both commensal microbes and osmotic stress. Our results reveal that osmotic stress is associated with the induction of developmental immunity in the absence of tissue damage and point out to the embryo skin as the first organ with full capacities to mount an innate immune response.


Subject(s)
Immunity, Innate/immunology , Keratinocytes/immunology , Skin/embryology , TRPV Cation Channels/immunology , Zebrafish Proteins/immunology , Zebrafish/embryology , Zebrafish/immunology , Animals , Embryo, Nonmammalian/immunology , Fluorescent Antibody Technique , Osmotic Pressure , Reverse Transcriptase Polymerase Chain Reaction , Skin/immunology , Transcriptome , Transfection
15.
Int J Colorectal Dis ; 33(9): 1251-1258, 2018 Sep.
Article in English | MEDLINE | ID: mdl-29721734

ABSTRACT

PURPOSE: The aim of the study was to evaluate the benefits of implementing Enhanced Recovery After Surgery (ERAS) protocols in elderly patients undergoing elective colorectal surgery. METHODS: A retrospective non-randomized cohort study was conducted from September 2012 to December 2016. We included patients ≥ 70 years undergoing elective colorectal surgery. Outcome measures, compliance with interventions, and postoperative complications of patients treated under ERAS were case-matched (based on gender, age, type of surgery, and the presence/absence of a temporal stoma) to a retrospective group of patients ≥ 70 years treated under conventional care. RESULTS: A total of 312 patients (156 ERAS vs. 156 non-ERAS) were included in the study. The ERAS group had a significant reduction of grade III/IV Dindo-Clavien's postoperative complications when compared with conventional care. ERAS had a positive effect in reducing anastomotic leakage (14.7% non-ERAS vs. 9%) and postoperative mortality (11.5% non-ERAS vs. 1.9% ERAS; p = 0.001). A reduction of 2 days in length of hospital stay was achieved after implementing ERAS (8 (6.75) vs. 6 (5.25); p < 0.0001), while readmission rates remained unaffected. The average of global compliance (GC) with all ERAS interventions was 42%. GC was significantly lower in patients with permanent/temporary stomas and in patients in whom an open approach was performed. CONCLUSION: In our experience, ERAS should be implemented without reservations in elderly patients expecting the same goals and benefits as with other age groups. Barriers in achieving a high compliance rate are common and will require a great effort in patient's education, an intensive perioperative care, and sometimes a change in the surgeons' practice.


Subject(s)
Colorectal Surgery , Postoperative Care , Recovery of Function , Aged , Aged, 80 and over , Digestive System Surgical Procedures , Female , Humans , Length of Stay , Male , Perioperative Care , Postoperative Complications , Retrospective Studies , Spain
16.
Rev Esp Enferm Dig ; 110(3): 138-144, 2018 03.
Article in English | MEDLINE | ID: mdl-29271228

ABSTRACT

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.


Subject(s)
Colonic Neoplasms/pathology , Colonic Neoplasms/surgery , Laparoscopy/methods , Aged , Aged, 80 and over , Cohort Studies , Colonic Neoplasms/mortality , Female , Humans , Laparoscopy/adverse effects , Laparoscopy/mortality , Male , Middle Aged , Neoplasm Recurrence, Local , Neoplasm Staging , Postoperative Complications/epidemiology , Postoperative Complications/mortality , Prospective Studies
17.
Rev Esp Enferm Dig ; 109(4): 241, 2017 04.
Article in English | MEDLINE | ID: mdl-28301946

ABSTRACT

Ninety-five percent of precursor lesions -high-grade squamous intraepithelial lesions (HSIL) and anal intraepithelial neoplasms (AIN)- and their progression to squamous anal cancer (AC) are induced by high-risk HPV (HR-HPV) serotypes 16 and 18. Their incidence is higher particularly in HIV-infected male patients who have sex with other males (HIV-MSM) (144/100,000/patients/year).


Subject(s)
Homosexuality, Male , Papillomaviridae , Anus Neoplasms , Carcinoma in Situ , HIV Infections/epidemiology , Health Services Needs and Demand , Humans , Male , Papillomavirus Infections , Pilot Projects , Risk Factors
18.
Rev Esp Enferm Dig ; 109(12): 865-866, 2017 Dec.
Article in English | MEDLINE | ID: mdl-29019251

ABSTRACT

Gastrointestinal duplications are unusual congenital malformations, nearly always diagnosed in childhood. Roughly 80% are cysts-like lesions and only a small percentage (4-18%) involves the colonic wall. Almost all are asymptomatic and therefore diagnosed as an incidental finding on imaging tests or when become complicated and present with perforation or bleeding. The need for an elective surgical treatment is controversial and should be indicated on an individual basis. This report is a case of an adult with a complete tubular colonic duplication found incidentally by colonoscopy that required surgical treatment due to perforation.


Subject(s)
Colon/abnormalities , Colon/diagnostic imaging , Colonoscopy , Colon/surgery , Female , Humans , Incidental Findings , Middle Aged , Tomography, X-Ray Computed
19.
Proteomics ; 16(8): 1280-90, 2016 Apr.
Article in English | MEDLINE | ID: mdl-26915739

ABSTRACT

Humoral response in cancer patients can be used for early cancer detection. By screening high-density protein microarrays with sera from colorectal cancer (CRC) patients and controls, we identified 16 tumor-associated antigens (TAAs) exhibiting high diagnostic value. This high number of TAAs requires the development of multiplex assays combining different antigens for a faster and more accurate prediction of CRC. Here, we have developed and optimized a bead-based assay using nine selected TAAs and two controls to provide a multiplex test for early CRC diagnosis. We screened a collection of 307 CRC patients' and control sera with the beads assay to identify and validate the best TAA combination for CRC detection. The multiplex bead-based assay exhibited a similar diagnostic performance to detect the humoral response in comparison to multiple ELISA analyses. After multivariate analysis, a panel composed of GTF2B, EDIL3, HCK, PIM1, STK4, and p53, together with gender and age, was identified as the best combination of TAAs for CRC diagnosis, achieving an AUC of 89.7%, with 66% sensitivity at 90.0% fixed specificity. The model was validated using bootstrapping analysis. In summary, we have developed a novel multiplex bead assay that after validation with a larger independent cohort of sera could be utilized in a high-throughput manner for population screening to facilitate the detection of early CRC patients.


Subject(s)
Antigens, Neoplasm/metabolism , Autoantibodies/metabolism , Colorectal Neoplasms/metabolism , Microspheres , Protein Array Analysis/methods , Aged , Antigens, Neoplasm/immunology , Autoantibodies/blood , Autoantibodies/immunology , Biomarkers, Tumor/immunology , Biomarkers, Tumor/metabolism , Calcium-Binding Proteins , Carrier Proteins/immunology , Carrier Proteins/metabolism , Cell Adhesion Molecules , Colorectal Neoplasms/blood , Colorectal Neoplasms/diagnosis , Enzyme-Linked Immunosorbent Assay , Female , Humans , Intracellular Signaling Peptides and Proteins , Male , Middle Aged , Multivariate Analysis , Prognosis , Protein Serine-Threonine Kinases/immunology , Protein Serine-Threonine Kinases/metabolism , Proto-Oncogene Proteins c-hck/immunology , Proto-Oncogene Proteins c-hck/metabolism , Proto-Oncogene Proteins c-pim-1/immunology , Proto-Oncogene Proteins c-pim-1/metabolism , Reproducibility of Results , Sensitivity and Specificity , Tumor Suppressor Protein p53/immunology , Tumor Suppressor Protein p53/metabolism
20.
Int J Colorectal Dis ; 31(9): 1625-31, 2016 Sep.
Article in English | MEDLINE | ID: mdl-27378580

ABSTRACT

PURPOSE: ERAS (enhanced recovery after surgery) programs have proven to reduce morbidity and hospital stay in colorectal surgery. However, the feasibility of these programs in elderly patients has been questioned. The aim of this study is to assess the implementation and outcomes of an ERAS program for colorectal cancer in elderly patients. METHODS: This is a multicenter observational study of a cohort of elderly patients undergoing colorectal surgery within an ERAS program. A total of 188 consecutive patients over 70 years who underwent elective colorectal surgery within an ERAS program at three institutions during a 2-year period were included. The compliance with the ERAS protocol interventions was measure. Complications were evaluated according to Clavien-Dindo classification. Data on length of stay and readmission rates were analyzed. RESULTS: Early intake and early mobilization were the most successfully carried out interventions. There was a global compliance rate of 56 % of patients for whom compliance was achieved with all measured interventions. The median hospital length of stay was 6 days. Almost 60 % of patients had no complications, 24 % had minor complications while 13 % had major complications; of them, 8 % patients were reoperated. The readmission rate was 6.4 %. CONCLUSIONS: ERAS after colorectal surgery in elderly patients presents as safe and feasible based on good reported outcomes of compliance rates, complications, readmissions, and needs for reoperation.


Subject(s)
Colorectal Surgery , Patient Compliance , Postoperative Care , Recovery of Function , Aged , Aged, 80 and over , Female , Humans , Male , Spain , Treatment Outcome
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