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1.
J Allergy Clin Immunol ; 151(3): 783-790.e5, 2023 03.
Article in English | MEDLINE | ID: mdl-36462956

ABSTRACT

BACKGROUND: Toll-like receptors (TLRs) mediate functions for host defense and inflammatory responses. TLR4 recognizes LPS, a component of gram-negative bacteria as well as host-derived endogenous ligands such as S100A8 and S100A9 proteins. OBJECTIVE: We sought to report phenotype and cellular function of individuals with complete TLR4 deficiency. METHODS: We performed genome sequencing and investigated exome and genome sequencing databases. Cellular responses were studied on primary monocytes, macrophages, and neutrophils, as well as cell lines using flow cytometry, reporter, and cytokine assays. RESULTS: We identified 2 individuals in a family of Qatari origin carrying a homozygous stop codon variant p.Q188X in TLR4 presenting with a variable phenotype (asymptomatic and inflammatory bowel disease consistent with severe perianal Crohn disease). A third individual with homozygous p.Y794X was identified in a population database. In contrast to hypomorphic polymorphisms p.D299G and p.T399I, the variants p.Q188X and p.Y794X completely abrogated LPS-induced cytokine responses whereas TLR2 response was normal. TLR4 deficiency causes a neutrophil CD62L shedding defect, whereas antimicrobial activity toward intracellular Salmonella was intact. CONCLUSIONS: Biallelic TLR4 deficiency in humans causes an inborn error of immunity in responding to LPS. This complements the spectrum of known primary immunodeficiencies, in particular myeloid differentiation primary response 88 (MYD88) or the IL-1 receptor-associated kinase 4 (IRAK4) deficiency that are downstream of TLR4 and TLR2 signaling.


Subject(s)
Toll-Like Receptor 2 , Toll-Like Receptor 4 , Humans , Toll-Like Receptor 4/genetics , Toll-Like Receptor 2/genetics , Lipopolysaccharides/pharmacology , Toll-Like Receptors/metabolism , Cytokines/metabolism , Myeloid Differentiation Factor 88/genetics
2.
Gut ; 72(3): 433-442, 2023 03.
Article in English | MEDLINE | ID: mdl-36171080

ABSTRACT

OBJECTIVES: We aimed to determine whether changes in acute severe colitis (ASC) management have translated to improved outcomes and to develop a simple model predicting steroid non-response on admission. DESIGN: Outcomes of 131 adult ASC admissions (117 patients) in Oxford, UK between 2015 and 2019 were compared with data from 1992 to 1993. All patients received standard treatment with intravenous corticosteroids and endoscopic disease activity scoring (Ulcerative Colitis Endoscopic Index of Severity (UCEIS)). Steroid non-response was defined as receiving medical rescue therapy or surgery. A predictive model developed in the Oxford cohort was validated in Australia and India (Gold Coast University Hospital 2015-2020, n=110; All India Institute of Medical Sciences, New Delhi 2018-2020, n=62). RESULTS: In the 2015-2019 Oxford cohort, 15% required colectomy during admission vs 29% in 1992-1993 (p=0.033), while 71 (54%) patients received medical rescue therapy (27% ciclosporin, 27% anti-tumour necrosis factor, compared with 27% ciclosporin in 1992-1993 (p=0.0015). Admission C reactive protein (CRP) (false discovery rate, p=0.00066), albumin (0.0066) and UCEIS scores (0.015) predicted steroid non-response. A four-point model was developed involving CRP of ≥100 mg/L (one point), albumin of ≤25 g/L (one point), and UCEIS score of ≥4 (1 point) or ≥7 (2 points). Patients scoring 0, 1, 2, 3 and 4 in the validation cohorts had steroid response rates of 100, 75.0%, 54.9%, 18.2% and 0%, respectively. Scoring of ≥3 was 84% (95% CI 0.70 to 0.98) predictive of steroid failure (OR 11.9, 95% CI 10.8 to 13.0). Colectomy rates in the validation cohorts were were 8%-11%. CONCLUSIONS: Emergency colectomy rates for ASC have halved in 25 years to 8%-15% worldwide. Patients who will not respond to corticosteroids are readily identified on admission and may be prioritised for early intensification of therapy.


Subject(s)
Biological Products , Colitis, Ulcerative , Colitis , Adult , Humans , Prognosis , Cyclosporine/therapeutic use , Biological Products/therapeutic use , Colitis, Ulcerative/drug therapy , Adrenal Cortex Hormones/therapeutic use , Steroids/therapeutic use , C-Reactive Protein/metabolism , Colitis/drug therapy , Albumins/therapeutic use , Severity of Illness Index , Colectomy , Treatment Outcome , Retrospective Studies
3.
Minim Invasive Surg ; 2022: 7578923, 2022.
Article in English | MEDLINE | ID: mdl-36406794

ABSTRACT

Purpose: Hartmann's reversal is a complex operation with a high morbidity rate. Minimally invasive surgery has been used to reduce the impact of surgery on fragile patients. The aim of this comparative study is to look at the results of Hartmann's reversal procedures with different approaches. Methods: All the patients who underwent Hartmann's reversal were collected retrospectively (124 cases). Sixty-four patients (50.4%) had an open operation, 6 cases (5%) were treated with a conventional laparoscopic approach, 34 patients (28.1%) underwent single incision laparoscopic surgery (SILS), and 20 (16.5%) required other additional trocars. Results: SILS operations were slightly longer than the open procedures (175 min vs 150 min), with the same rate of postoperative complications and reoperations (p = 0.83 and p = 0.42), but with a shorter hospital stay (5 days p = 0.007). Age (p = 0.03), long operative time (p = 0.01), and ASA score (p = 0.05) were identified as independent factors affecting postoperative morbidity. The grade of adhesions caused a longer operative time (p = 0.001) and a higher risk of conversion (p < 0.001), and short rectal stump increased the risk of protective loop ileostomy (p = 0.008). Patients with grade 2-3 of adhesions had a longer length of stay (p = 0.05). Conclusions: Minimally invasive procedures had a shorter hospital stay and did not show any increase in morbidity rate when compared with open cases. Age, longer operative time, and ASA score increased the risk of postoperative complications. Furthermore, patients with a short rectal stump had a higher chance of having a defunctioning ileostomy.

4.
Front Surg ; 9: 867830, 2022.
Article in English | MEDLINE | ID: mdl-35592128

ABSTRACT

Crohn's disease (CD) is increasing globally, and the disease location and behavior are changing toward more colonic as well as inflammatory behavior. Surgery was previously mainly performed due to ileal/ileocaecal location and stricturing behavior, why many anticipate the surgical load to decrease. There are, however, the same time data showing an increasing complexity among patients at the time of surgery with an increasing number of patients with the abdominal perforating disease, induced by the disease itself, at the time of surgery and thus a more complex surgery as well as the post-operative outcome. The other major cause of abdominal penetrating CD is secondary to surgical complications, e.g., anastomotic dehiscence or inadvertent enterotomies. To improve the care for patients with penetrating abdominal CD in general, and in the peri-operative phase in particular, the use of multidisciplinary team discussions is essential. In this study, we will try to give an overview of penetrating abdominal CD today and how this situation may be handled. Proper surgical planning will decrease the risk of surgically induced penetrating disease and improve the outcome when penetrating disease is already established. It is important to evaluate patients prior to surgery and optimize them with enteral nutrition (or parenteral if enteral nutrition is ineffective) and treat abdominal sepsis with drainage and antibiotics.

6.
Updates Surg ; 74(2): 591-597, 2022 Apr.
Article in English | MEDLINE | ID: mdl-34231164

ABSTRACT

Accurate preoperative staging of colorectal cancers is critical in selecting patients for neoadjuvant therapy prior to resection. Inaccurate staging, particularly understaging, may lead to involved resection margins and poor oncological outcomes. Our aim is to determine preoperative imaging accuracy of colorectal cancers compared to histopathology and define the effect of inaccurate staging on patient selection for neoadjuvant treatment(NT). Staging and treatment were determined for patients undergoing colorectal resections for adenocarcinomas in a single tertiary centre(2016-2020). Data were obtained for 948 patients. The staging was correct for both T and N stage in 19.68% of colon cancer patients. T stage was under-staged in 18.58%. At resection, 23 patients (3.36%) had involved pathological margins; only 7 of which had been predicted by pre-operative staging. However, the staging was correct for both T and N stage in 53.85% of rectal cancer patients. T stage was understaged in 26.89%. Thirteen patients had involved(R1)margins; T4 had been accurately predicted in all of these cases. There was a general trend in understaging both the tumor and lymphonodal involvement (T p < 0.00001 N p < 0.00001) causing a failure in administrating NT in 0.1% of patients with colon tumor, but not with rectal cancer. Preoperative radiological staging tended to understage both colonic and rectal cancers. In colonic tumours this may lead to a misled opportunity to treat with neoadjuvant therapy, resulting in involved margins at resection.


Subject(s)
Adenocarcinoma , Colonic Neoplasms , Rectal Neoplasms , Adenocarcinoma/pathology , Colonic Neoplasms/pathology , Humans , Margins of Excision , Neoadjuvant Therapy , Neoplasm Staging , Rectal Neoplasms/surgery
7.
Surg Pract ; 26(1): 27-33, 2022 Feb.
Article in English | MEDLINE | ID: mdl-34899957

ABSTRACT

Aim: The coronavirus pandemic has significantly disrupted the way we deliver healthcare worldwide. We have been flexible and creative in order to continue providing elective colorectal cancer operations and to restart services for benign cases during the recovery period of the pandemic. In this paper, we describe the impact of coronavirus on our elective services and how we have implemented new patient pathways to allow us to continue providing patient care. Patients and Methods: Data on major colorectal elective resections were prospectively collected in an Enhanced Recovery After Surgery (ERAS) database. Data on the number of proctology cases and telemed appointments were collected from the hospital theatre information management system and electronic patient record system, respectively. Results: During the pandemic, there was a complete shift towards cancer cases, with benign services and proctology cases being placed on hold. Hospital length of stay was reduced. We implemented earlier hospital discharge and more intense telephone follow-up after elective major surgery. This has not resulted in an increase in postoperative complications, nor any increase in readmission to hospital. During the recovery phase, we have introduced a higher proportion of telemed consultations, including one-stop telemed proctology clinics, resulting in straight to tests or investigations. Conclusion: We have created a streamlined multidisciplinary pathway to reinstate our elective colorectal services as soon as possible and to minimise potential harm caused to patients whose treatment have been delayed. We anticipate many of these changes will be permanently incorporated into our clinical practice once the pandemic is over.

8.
World J Surg ; 45(3): 655-661, 2021 03.
Article in English | MEDLINE | ID: mdl-33423099

ABSTRACT

AIM: Cancer surgery in the COVID-19 pandemic presents many new challenges. For each patient, the risk of contracting COVID-19 during the perioperative period, with the potential for life-threatening sequelae (1), has to be weighed against the risk of delaying treatment. We assessed the response and short-term outcomes from elective colorectal cancer surgery during the pandemic at our institution. METHOD: We report a prospective cohort study of all elective colorectal surgery cases performed at our Trust during the 11 weeks following the national UK lockdown on 23rd March 2020, compared with the same time period in 2019. RESULTS: Eighty-five colorectal operations were performed during the 2020 (COVID) time period, and 179 performed in the 2019 (non-COVID) time period. A significantly higher proportion of cases during the COVID period were cancer-related (66% vs 26%, p < 0.00001). There was no difference in length of hospital stay, complications or readmissions. There were no mortalities in either cohort. Among the cancer patients, there were no differences in TMN staging, R1 resection rate or lymph node yields. No elective patient tested positive for COVID-19 during the perioperative period. CONCLUSION: At the height of the COVID pandemic, we maintained delivery the of high-quality elective colorectal cancer surgery, with no worsening of short-term outcomes and no compromise in the quality of cancer resections. Ongoing monitoring of this cohort is essential. The risks associated with COVID-19 will continue for some time, necessitating adaptive responses to maintain high-quality cancer services.


Subject(s)
COVID-19/epidemiology , Digestive System Surgical Procedures/statistics & numerical data , Adult , Aged , Aged, 80 and over , COVID-19 Testing , Cohort Studies , Colorectal Neoplasms/epidemiology , Colorectal Neoplasms/surgery , Female , Humans , Length of Stay/statistics & numerical data , Lymph Node Excision/statistics & numerical data , Male , Middle Aged , Pandemics , Patient Readmission/statistics & numerical data , Postoperative Complications/epidemiology , United Kingdom/epidemiology , Young Adult
9.
Dis Colon Rectum ; 63(2): 200-206, 2020 02.
Article in English | MEDLINE | ID: mdl-31842162

ABSTRACT

BACKGROUND: Tobacco smoking is a known risk factor for recurrence of Crohn's disease after surgical resection. OBJECTIVE: This study assessed the effect of smoking cessation on long-term surgical recurrence after primary ileocolic resection for Crohn's disease. DESIGN: A retrospective review of a prospectively maintained database was conducted. SETTINGS: Patient demographic data and medical and surgical details were combined from 2 specialist centers. After ethical approval, patients were contacted in case of missing data regarding smoking habit. PATIENTS: All patients undergoing ileocolic resection between 2000 and 2012 for histologically confirmed Crohn's disease were included. Those with previous intestinal resection, strictureplasty for Crohn's disease, leak after ileocolic resection, or who were never reversed were excluded. MAIN OUTCOME MEASURES: The primary end point was surgical recurrence measured by Kaplan-Meier survival analysis and secondary medical therapy at time of follow-up. RESULTS: Over a 12-year period, 290 patients underwent ileocolic resection. Full smoking data were available for 242 (83%) of 290 patients. There were 169 nonsmokers (70%; group 1), 42 active smokers at the time of ileocolic resection who continued smoking up to last follow-up (17%; group 2), and 31 (13%) who quit smoking after ileocolic resection (group 3). The median time of smoking exposure after ileocolic resection for group 3 was 3 years (interquartile range, 0-6 y), and median follow-up time for the whole group was 112 months (9 mo; interquartile range, 84-148 mo). Kaplan-Meier survival analysis showed a significantly higher surgical recurrence rate for group 2 compared with group 3 (16/42 (38%) vs 3/31 (10%); p = 0.02; risk ratio = 3.9 (95% CI, 1-12)). In addition, significantly more patients in group 2 without surgical recurrence received immunomodulatory maintenance therapy compared with group 3 (12/26 (46%) vs 4/28 (14%); p = 0.01; risk ratio = 3.2 (95% CI, 1-9)). LIMITATIONS: The study was limited by its retrospective design and small number of patients. CONCLUSIONS: Smoking cessation after primary ileocolic resection for Crohn's disease may significantly reduce long-term risk of surgical recurrence and is associated with less use of maintenance therapy. See Video Abstract at http://links.lww.com/DCR/B86. ¿DEJAR DE FUMAR REDUCE LA RECURRENCIA QUIRÚRGICA DESPUÉS DE LA RESECCIÓN ILEOCÓLICA PRIMARIA PARA LA ENFERMEDAD DE CROHN?: Fumar tabaco es un factor de riesgo conocido para la recurrencia de la enfermedad de Crohn después de la resección quirúrgica.Evaluar el efecto de dejar de fumar en la recurrencia quirúrgica a largo plazo después de la resección ileocólica primaria para la enfermedad de Crohn.Revisión retrospectiva de una base de datos mantenida prospectivamente.Se combinaron datos demográficos del paciente, así como detalles médicos y quirúrgicos de dos centros especializados. Después de la aprobación ética, se contactó a los pacientes en caso de falta de datos sobre el hábito de fumar.Todos los pacientes sometidos a resección ileocólica entre 2000 y 2012 por enfermedad de Crohn confirmada histológicamente. Se excluyeron aquellos con resección intestinal previa, estenosis por enfermedad de Crohn, fuga después de resección ileocólica o que nunca se revirtieron.La principal variable fue la recurrencia quirúrgica medida por análisis de supervivencia de Kaplan-Meier, terapia médica secundaria en el momento del seguimiento.Durante un período de 12 años, 290 pacientes fueron sometidos a resección ileocólica. Se dispuso de datos completos sobre el tabaquismo para 242/290 (83%). Hubo 169 no fumadores (70%) (grupo 1), 42 (17%) fumadores activos en el momento de la resección ileocólica que continuaron fumando hasta el último seguimiento (grupo 2) y 31 (13%) que dejaron de fumar después de resección ileocólica (grupo 3). La mediana del tiempo de exposición al tabaquismo después de la resección ileocólica para el grupo 3 fue de 3 años (IQR 0-6) y la mediana del tiempo de seguimiento para todo el grupo fue de 112 meses (9 años) (IQR 84-148). El análisis de supervivencia de Kaplan-Meier mostró una tasa de recurrencia quirúrgica significativamente mayor para el grupo 2 en comparación con el grupo 3 (16/42 (38%) frente a 3/31 (10%), p = 0.02; razón de riesgo 3.9 (IC 95% 1-12)). Además, un número significativamente mayor de pacientes del grupo 2 sin recurrencia quirúrgica recibieron terapia de mantenimiento inmunomoduladora en comparación con el grupo 3 (12/26 (46%) frente a 4/28 (14%), p = 0.01; razón de riesgo 3.2 (IC 95% 1-9)).Diseño retrospectivo y pequeño número de pacientes.Dejar de fumar después de la resección ileocólica primaria para la enfermedad de Crohn puede reducir significativamente el riesgo a largo plazo de recurrencia quirúrgica y se asocia con un menor uso del tratamiento de mantenimiento. Consulte Video Resumen en http://links.lww.com/DCR/B86. (Traducción-Dr. Gonzalo Federico Hagerman).


Subject(s)
Crohn Disease/surgery , Intestines/surgery , Reoperation/statistics & numerical data , Smoking Cessation/methods , Adolescent , Adult , Aged , Anastomosis, Surgical , Crohn Disease/epidemiology , Crohn Disease/pathology , Female , Follow-Up Studies , Humans , Immunomodulation/physiology , Inhalation Exposure/adverse effects , Intestines/pathology , Male , Middle Aged , Recurrence , Retrospective Studies , Smoking Cessation/statistics & numerical data , Survival Analysis , Young Adult
11.
Scand J Gastroenterol ; 53(12): 1443-1452, 2018 Dec.
Article in English | MEDLINE | ID: mdl-30451043

ABSTRACT

OBJECTIVES: Acute severe colitis requires surgery in around 30% of the cases. Total colectomy with ileostomy is the standard procedure with distinct advantages to a laparoscopic approach. Less agreement exists regarding the formation or configuration of the retained rectal stump and its short-term and long-term management. In this review, aspects of management of the rectal remnant, including perioperative considerations, potential complications, medical treatment, surveillance and implications for proctectomy and reconstructive surgery are explored. METHODS: A thorough literature review exploring the PubMed and EMBASE databases was undertaken to clarify the evidence base surrounding areas of controversy in the surgical approach to acute severe colitis. In particular, focus was given to evidence surrounding management of the rectal remnant. RESULTS: There is a paucity of high quality evidence for optimal management of the rectal stump following colectomy, and randomised trials are lacking. Establishment of laparoscopic colectomy has been associated with distinct advantages as well as the emergence of unique considerations, including those specific to rectal remnant management. CONCLUSIONS: Early surgical involvement and a multidisciplinary approach to the management of acute severe colitis are advocated. Laparoscopic subtotal colectomy and ileostomy should be the operation of choice, with division of the rectum at the pelvic brim leaving a closed intraperitoneal remnant. If the rectum is severely inflamed, a mucus fistula may be useful, and an indwelling rectal catheter is probably advantageous to reduce the complications associated with stump dehiscence. Patients electing not to proceed to proctectomy should undergo surveillance for dysplasia of the rectum.


Subject(s)
Colectomy/methods , Colitis/surgery , Ileostomy/methods , Rectum/surgery , Acute Disease , Humans , Postoperative Complications/epidemiology , Postoperative Complications/prevention & control , Proctocolectomy, Restorative , Surgical Wound Infection/epidemiology , Surgical Wound Infection/prevention & control , Treatment Outcome
12.
Surg Endosc ; 32(9): 4036-4043, 2018 09.
Article in English | MEDLINE | ID: mdl-29785456

ABSTRACT

BACKGROUND: Iatrogenic ureteric injury is a serious complication of colorectal surgery. Incidence is estimated to be between 0.3 and 1.5%. Of all ureteric injuries, 9% occur during colorectal procedures. Ureteric stents are utilised as a method to reduce the risk of injury; however, these are not without risk and do not guarantee prevention of injury. Fluorescence is a safe and effective alternative for intraoperative ureteric localisation. This proof of principle study aims to assess the use of methylene blue to fluoresce the ureter during colorectal surgery. METHOD: Patients undergoing elective colorectal surgery were included in this open label, non-randomised study. Methylene blue was administered intravenously at varying doses (0.25-1 mg/kg) over 5 min, 10-15 min prior to entering 'ureteric territory.' Fluorescence was assessed using the PINPOINT Deep Red laparoscopic system at fixed time points by the surgeon and an independent observer. RESULTS: 42 patients received methylene blue; 2 patients were excluded from analysis. Of the 69 ureters assessed, 64 were seen under fluorescence. Of these, 14 were not visible under white light. 50 ureters were observed with both fluorescence and white light with 14 of these being seen earlier with fluorescence. In ten cases, fluorescence revealed the ureter to be in a different location than suspected. CONCLUSION: Fluorescence is a promising method to allow visualisation of the ureter, where it is not identified easily under standard operative conditions, thereby improving safety and reducing operative time and difficulty.


Subject(s)
Fluorescence , Iatrogenic Disease/prevention & control , Intraoperative Complications/prevention & control , Methylene Blue , Ureter/diagnostic imaging , Adult , Aged , Aged, 80 and over , Colon/surgery , Female , Humans , Laparoscopy , Male , Middle Aged , Rectum/surgery
13.
Gastrointest Endosc ; 86(6): 1088-1099.e5, 2017 Dec.
Article in English | MEDLINE | ID: mdl-28882578

ABSTRACT

BACKGROUND AND AIMS: There is uncertainty regarding the optimal management of endoscopically invisible (flat) low-grade dysplasia in ulcerative colitis. Such a finding does not currently provide an automatic indication for colectomy; however, a recommendation of surveillance instead of surgery is controversial. The aim of this study was to determine the clinical and cost-effectiveness of colonoscopic surveillance versus colectomy for endoscopically invisible low-grade dysplasia of the colon in ulcerative colitis. METHODS: A Markov model was used to evaluate the costs and health outcomes of surveillance and surgery over a 20-year timeframe. Outcomes evaluated were life years gained and quality-adjusted life years (QALYs). Cohorts of patients aged 25 to 75 were modeled, including estimates from a validated surgical risk calculator and considering none, 1, or both of 2 key comorbidities: heart failure and obstructive airway disease. RESULTS: Surveillance is associated with more life years and QALYs compared with surgery from age 61 for those with no comorbidities, age 51 for those with 1 comorbidity and age 25 for those with 2 comorbidities. At the current United Kingdom National Institute for Health and Care Excellence threshold of $25,800 per QALY, ongoing surveillance was cost-effective at age 65 in those without comorbidities and at age 60 in those with either 1 or more comorbidities. CONCLUSIONS: Surveillance can be recommended from age 65 for those with no comorbidities; however, in younger patients with typical postsurgical quality of life, colectomy may be more effective clinically and more cost-effective. The results were sensitive to the colorectal cancer incidence rate in patients under surveillance and to quality of life after surgery.


Subject(s)
Colectomy/economics , Colitis, Ulcerative/diagnostic imaging , Colitis, Ulcerative/therapy , Colonoscopy/economics , Watchful Waiting/economics , Adult , Age Factors , Aged , Airway Obstruction/complications , Colitis, Ulcerative/complications , Colitis, Ulcerative/pathology , Cost-Benefit Analysis , Heart Failure/complications , Humans , Markov Chains , Middle Aged , Models, Economic , Quality-Adjusted Life Years
14.
Dis Colon Rectum ; 60(6): 577-585, 2017 Jun.
Article in English | MEDLINE | ID: mdl-28481851

ABSTRACT

BACKGROUND: There remains a lack of international consensus on the appropriate management of lateral nodal disease. Although the East manages this more aggressively with lateral lymph node dissections, the West aims to eradicate small-volume disease with neoadjuvant chemoradiotherapy and lateral nodal disease is not considered for routine surgical treatment. However, recent studies have shown that, despite neoadjuvant treatment, a significant number of patients with lateral nodal disease develop local recurrence in the lateral compartment after total mesorectal excision. OBJECTIVE: The aim of this study is to assess the role of the pretreatment features of lateral nodes on MRI in regard to local recurrence. DESIGN: All patients operated on for low locally advanced rectal cancer over a 5-year period were evaluated retrospectively. SETTINGS: This study was conducted at a single expert center. PATIENTS: The MRIs of a total of 313 patients were reviewed, and only those with rectal cancers up to 8 cm from the anorectal junction, measured on MRI, were selected. This left 185 patients; of these, 58 patients had clinical T1 or T2 tumors as assessed on MRI, identifying 127 patients who had cT3/T4 tumors that were included in this study. MAIN OUTCOME MEASURES: The primary outcomes measured were lateral local recurrence and multivariate analyses. RESULTS: The lateral local recurrence rate was significantly higher (33.3% 4-year rate) in patients with nodes larger than 10 mm than in patients with smaller nodes (10.1%, p = 0.03), despite patients being irradiated in the lateral compartment. LIMITATIONS: Because this is a relatively uncommon disease, patient numbers are low, and a multicenter study is needed to further address lateral nodal disease in low rectal cancer. CONCLUSIONS: Chemoradiotherapy with total mesorectal excision might not be sufficient in a selected group of patients. Further research is needed about which pretreatment features of the lateral nodes predict local recurrence and what is needed to prevent these from developing. See Video Abstract at http://links.lww.com/DCR/A338.


Subject(s)
Adenocarcinoma/pathology , Adenocarcinoma/therapy , Lymph Nodes/pathology , Neoplasm Recurrence, Local/pathology , Rectal Neoplasms/pathology , Rectal Neoplasms/therapy , Adenocarcinoma/mortality , Adult , Aged , Aged, 80 and over , Chemoradiotherapy , Female , Humans , Lymphatic Metastasis , Magnetic Resonance Imaging , Male , Middle Aged , Multivariate Analysis , Rectal Neoplasms/mortality , Retrospective Studies
15.
Surgery ; 159(5): 1237-48, 2016 May.
Article in English | MEDLINE | ID: mdl-26936524

ABSTRACT

BACKGROUND: The human intestine is a complex group of organs, highly specialized in processing food and providing nutrients to the body. It is under constant threat from microbials and toxins and has therefore developed a number of protective mechanisms. One important mechanism is the constant shedding of epithelial cells into the lumen; another is the production and maintenance of a double-layered mucous boundary in which there is continuous sampling of the luminal microbiota and a persistent presence of antimicrobial enzymes. However, the gut needs commensal bacteria to effectively break down food into absorbable nutrients, which necessitates constant communication between the luminal bacteria and the intestinal immune cells in homeostasis. Disruption of homeostasis, for whatever reason, will give rise to (chronic) inflammation. DISCUSSION: Both medical and surgical management of this disruption is discussed.


Subject(s)
Gastrointestinal Microbiome/physiology , Homeostasis/physiology , Inflammatory Bowel Diseases/physiopathology , Intestinal Mucosa/physiopathology , Stem Cells/physiology , Appendix/immunology , Appendix/microbiology , Appendix/physiopathology , Gastrointestinal Microbiome/immunology , Homeostasis/immunology , Humans , Inflammatory Bowel Diseases/immunology , Inflammatory Bowel Diseases/microbiology , Inflammatory Bowel Diseases/therapy , Intestinal Mucosa/cytology , Intestinal Mucosa/immunology , Intestinal Mucosa/microbiology , Signal Transduction/immunology , Signal Transduction/physiology , Stem Cell Transplantation , Stem Cells/immunology , Stem Cells/microbiology
17.
Dis Colon Rectum ; 58(10): 938-42, 2015 Oct.
Article in English | MEDLINE | ID: mdl-26347965

ABSTRACT

BACKGROUND: Noninflammatory masses in the ischiorectal fossa are rare. OBJECTIVE: This study aimed to review our experience with ischiorectal fossa tumors and to address the question of whether percutaneous biopsy should be undertaken. DESIGN: This is a retrospective study. SETTINGS: This study was conducted at a tertiary institution. PATIENTS: From April 2007 to November 2014, all consecutive ischiorectal fossa masses treated in a referral center were retrospectively reviewed. They were all presented and discussed in a multidisciplinary team meeting. Magnetic resonance imaging was performed in all the patients. Inflammatory pathologies, such as abscess, were excluded from the analysis. INTERVENTIONS: Percutaneous biopsy and surgical excision of ischiorectal fossa tumors were reviewed. MAIN OUTCOME MEASURES: Perioperative, pathological, and oncological outcomes were measured. RESULTS: Eleven patients were identified (8 female; median age, 50 years; range, 25-90). Percutaneous biopsy was undertaken in 8 patients. All biopsies were diagnostic and altered preoperative management in 3 cases (aggressive angiomyxoma (n = 2), desmoid fibromatosis (n = 1)). Overall final diagnosis was benign in 3 patients, locally aggressive neoplasm in 3, and malignant in 5 cases (leiomyosarcomas (n = 2), liposarcomas (n = 2), and angiomyosarcoma (n = 1)). Surgical approaches were perineal in 8 patients, abdominoperineal in 1 patient, and totally abdominal in 1 patient. One patient (age 90 years) was managed nonsurgically. After resection, 2 positive margins were observed (R1 rate, 20%). After a mean follow-up of 24.3 months, 3 patients have experienced local recurrence, which required further surgery in 2 cases. LIMITATIONS: This study is limited by the small number of patients. CONCLUSIONS: Noninflammatory masses in the ischiorectal fossa are rare, but they are commonly malignant and should be imaged by MRI. Unless the radiological appearances are diagnostic, percutaneous biopsy is recommended and alters management in about one-third of cases.


Subject(s)
Biopsy/methods , Fibromatosis, Aggressive , Myxoma , Neoplasm Recurrence, Local/prevention & control , Pelvic Neoplasms , Diagnosis, Differential , Dissection/adverse effects , Dissection/methods , Female , Fibromatosis, Aggressive/pathology , Fibromatosis, Aggressive/surgery , Humans , Magnetic Resonance Imaging/methods , Male , Middle Aged , Myxoma/pathology , Myxoma/surgery , Outcome Assessment, Health Care , Pelvic Neoplasms/diagnosis , Pelvic Neoplasms/pathology , Pelvic Neoplasms/surgery , Reoperation , Reproducibility of Results , Retrospective Studies , United Kingdom
18.
J Food Prot ; 77(11): 1889-96, 2014 Nov.
Article in English | MEDLINE | ID: mdl-25364922

ABSTRACT

Inoculated beef trim containing a cocktail of green fluorescent protein-marked Escherichia coli biotype I cultures as surrogates for E. coli O157:H7 was introduced into two large, commercial grinding facilities capable of producing 180,000 kg of ground product in 1 day. Three repetitions were performed over 3 days. Sampling occurred at three different points within the process: postprimary grind, postsecondary grind-blender, and postpackaging. Resulting data show that, as the inoculated meat passes through the system, the presence of the marked surrogate quickly diminishes. The depletion rates are directly related to the amount of product in kilograms (represented by time) that has passed through the system, but these rates vary with each step of the process. The primary grinder appears to rid itself of the contaminant the most quickly; in all repetitions, the contaminant was not detected within 5 min of introduction of the contaminated combo bin into the system, which in all cases, was prior to the introduction of a second combo bin and within 1,800 kg of product. After the blending step and subsequent secondary grinding, the contaminant was detected in product produced from both the parent combo and the combo bin added directly after the parent combo bin; however, for those days on which three combo bins (approximately 2,700 kg) were available for sampling, the contaminant was not detected from product representing the third combo bin. Similarly, at the packaging step, the contaminant was detected in the product produced by both the parent and second combo bins; however, on those days when a third combo bin was available for sampling (repetitions 2 and 3), the contaminant was not detected from product produced from the third combo bin.


Subject(s)
Escherichia coli/isolation & purification , Food Contamination/prevention & control , Food Handling/instrumentation , Food Handling/methods , Meat/microbiology , Animals , Cattle , Colony Count, Microbial , Escherichia coli/genetics , Escherichia coli/metabolism , Food Contamination/analysis , Food Microbiology , Green Fluorescent Proteins/genetics , Green Fluorescent Proteins/metabolism , Meat/economics
19.
Surg Endosc ; 28(7): 2221-6, 2014 Jul.
Article in English | MEDLINE | ID: mdl-24566744

ABSTRACT

BACKGROUND: Anastomotic leakage is a devastating complication of colorectal surgery. However, there is no technology indicative of in situ perfusion of a laparoscopic colorectal anastomosis. METHODS: We detail the use of near-infrared (NIR) laparoscopy (PinPoint System, NOVADAQ, Canada) in association with fluorophore [indocyanine green (ICG), 2.5 mg/ml] injection in 30 consecutive patients who underwent elective minimally invasive colorectal resection using the simultaneous appearance of the cecum or distal ileum as positive control. RESULTS: The median (range) age of the patients was 64 (40-81) years with a median (range) BMI of 26.7 (20-35.5) kg/m(2). Twenty-four patients had left-sided resections (including six low anterior resections) and six had right-sided resections. Of the total, 25 operations were cancer resections and five were for benign disease [either diverticular strictures (n = 3) or Crohn's disease (n = 2)]. A high-quality intraoperative ICG angiogram was achieved in 29/30 patients. After ICG injection, median (range) time to perfusion fluorescence was 35 (15-45) s. Median (range) added time for the technique was 5 (3-9) min. Anastomotic perfusion was documented as satisfactory in every successful case and encouraged avoidance of defunctioning stomas in three patients with low anastomoses. There were no postoperative anastomotic leaks. CONCLUSION: Perfusion angiography of colorectal anastomosis at the time of their laparoscopic construction is feasible and readily achievable with minimal added intraoperative time. Further work is required to determine optimum sensitivity and threshold levels for assessment of perfusion sufficiency, in particular with regard to anastomotic viability.


Subject(s)
Colon/blood supply , Colon/surgery , Fluorescein Angiography/methods , Laparoscopy , Rectum/blood supply , Rectum/surgery , Adult , Aged , Aged, 80 and over , Anastomosis, Surgical , Colonic Diseases/surgery , Coloring Agents , Female , Humans , Indocyanine Green , Male , Middle Aged , Rectal Diseases/surgery , Regional Blood Flow
20.
J Food Prot ; 75(2): 405-7, 2012 Feb.
Article in English | MEDLINE | ID: mdl-22289606

ABSTRACT

Pork tissue samples that tested positive and negative by the Charm II tetracycline test screening method in the slaughter plant laboratory were tested with the modified AOAC International liquid chromatography tandem mass spectrometry (LC-MS-MS) method 995.09 to determine the predictive value of the screening method at detecting total tetracyclines at 10 µg/kg of tissue, in compliance with Russian import regulations. There were 218 presumptive-positive tetracycline samples of 4,195 randomly tested hogs. Of these screening test positive samples, 83% (182) were positive, >10 µg/kg by LC-MS-MS; 12.8% (28) were false violative, greater than limit of detection (LOD) but <10 µg/kg; and 4.2% (8) were not detected at the LC-MS-MS LOD. The 36 false-violative and not-detected samples represent 1% of the total samples screened. Twenty-seven of 30 randomly selected tetracycline screening negative samples tested below the LC-MS-MS LOD, and 3 samples tested <3 µg/kg chlortetracycline. Results indicate that the Charm II tetracycline test is effective at predicting hogs containing >10 µg/kg total tetracyclines in compliance with Russian import regulations.


Subject(s)
Drug Residues/analysis , Food Analysis/methods , Food Contamination/analysis , Swine , Tetracycline/isolation & purification , Animals , Anti-Bacterial Agents/isolation & purification , Chromatography, Liquid/methods , Tandem Mass Spectrometry/methods
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