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1.
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
2.
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.

3.
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
4.
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
5.
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
6.
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
7.
Int J Cancer ; 126(8): 1910-1919, 2010 Apr 15.
Article in English | MEDLINE | ID: mdl-19588499

ABSTRACT

This pilot study aimed to assess an original test based on the analysis of exfoliated colonocytes as a new approach to colorectal cancer (CRC) detection. DNA was isolated from exfoliated cells collected from the surface of the rectal mucosa by a standardized minimally invasive procedure in a case-control trial involving 66 patients with CRC diagnosis and 110 healthy volunteers (age 50-70). PicoGreen staining and quantitative real-time PCR (QRTPCR) were used for DNA quantification. Mean DNA scores in microg/ml obtained for the control and cancer groups were 2.1 (95% CI 1.7-2.5) and 9.0 (CI 6.7-11.2) respectively (p < 0.001) for PicoGreen and 0.8 (CI 0.6-0.9) and 3.8 (CI 1.9-5.7) respectively (p = 0.003) for QRTPCR. The PicoGreen assay better detected CRC presence. At DNA score cut-off point of 2.5 microg/ml this assay gave sensitivities of 77.8% (CI 52.4-93.6) for proximal tumours, 91.4% (CI 76.9-98.2) for distal CRC and 86.8% (CI 74.7-94.5) for all CRC with specificity at 74.0% (CI 64.0-82.4). Increasing the cut-off point to 5.0 microg/ml resulted in sensitivities of 38.9% (CI 17.3-64.3) for proximal tumours, 71.4% (CI 53.7-85.4) for distal CRC and 60.4% (CI 46.0-73.5) for all CRC. Specificity for this cut-off point increased to 94.8% (CI 88.3-98.3). The new procedure of exfoliated cell collection from the surface of the rectal mucosa is a simple, safe and well-tolerated technique providing high quality cells. These early results suggest that exfoliated cell collection in combination with DNA quantification can potentially be employed as a tool for CRC early detection.


Subject(s)
Colorectal Neoplasms/diagnosis , Colorectal Neoplasms/genetics , Cytodiagnosis/methods , DNA, Neoplasm/analysis , Aged , Case-Control Studies , Female , Humans , Male , Middle Aged , Pilot Projects , ROC Curve , Reverse Transcriptase Polymerase Chain Reaction , Sensitivity and Specificity
8.
Cancer Immun ; 7: 7, 2007 Mar 28.
Article in English | MEDLINE | ID: mdl-17388261

ABSTRACT

Recent results have shown a correlation between survival and frequency of tumour infiltrating T lymphocytes in colorectal cancer patients. However, it remains unclear whether the frequency of regulatory T cells is higher in colorectal cancer as compared to normal colon. To address this question we analysed the frequency and function of regulatory T cells in the peripheral blood and tumour infiltrating lymphocytes of colorectal cancer patients. The proportion of regulatory T cells in the peripheral blood of colorectal cancer patients (mean 8%) was significantly higher than that in normal controls (mean 2.2%). There were significantly more regulatory T cells in tumour infiltrating lymphocytes (mean 19.2%) compared to lymphocytes from an autologous non-malignant portion of the colon (mean 9%). Regulatory T cells from colorectal cancer patients were FOXP3 positive and suppressed the proliferation of autologous CD4+ CD25- cells. A higher density of tumour infiltrating regulatory T cells was found in patients with advanced as compared to early disease. These results support the hypothesis that increased numbers of regulatory T cells in the blood and tumours of colorectal cancer patients may influence the immune response against cancer and suggest that strategies to overcome regulatory T cell activity may be beneficial in the treatment of human colorectal cancer.


Subject(s)
Colorectal Neoplasms/immunology , T-Lymphocytes, Regulatory/physiology , Case-Control Studies , Colon/immunology , Colorectal Neoplasms/blood , Forkhead Transcription Factors/metabolism , Humans
9.
J Immunol ; 178(5): 2908-15, 2007 Mar 01.
Article in English | MEDLINE | ID: mdl-17312135

ABSTRACT

Recent results have shown a correlation between survival and frequency of tumor-infiltrating T cells in colorectal cancer patients. However, the mechanisms controlling the ability of human T lymphocytes to infiltrate colon carcinoma remain unclear. Although, it is known that expression of the integrin CD103alpha(E)/beta(7) by intraepithelial lymphocytes controls the retention of lymphocytes in epithelial layers, very little is known about the expression of intestinal homing receptors in human T lymphocytes. In particular, it remains unknown whether expression of CD103/beta(7) by human colon cancer-specific T lymphocytes is controlled by recognition of tumor Ags and is imprinted during T cell priming, facilitating its expression during memory T cell activation. In this study, we demonstrate that expression of CD103/beta(7) in human colon carcinoma-specific CTL is synergistically enhanced by the simultaneous TGF-beta1 stimulation and Ag recognition. These results were confirmed by using a panel of human CTL clones. Finally, we show that priming of naive CD8(+) T cells in the presence of TGF-beta1 ensures up-regulation of CD103/beta(7) in recall responses, at concentrations of TGF-beta1 significantly lower than those required by memory T cells primed in the absence of TGF-beta1. These results indicate a role of TGF-beta1 during T cell priming in modulating expression of CD103/beta(7) and controlling retention of human memory CD8(+) T cells into tumor epithelium.


Subject(s)
Antigens, CD/immunology , Antigens, Neoplasm/immunology , CD8-Positive T-Lymphocytes/immunology , Colonic Neoplasms/immunology , Gene Expression Regulation, Neoplastic/immunology , Immunologic Memory , Integrin alpha Chains/immunology , Aged , Antigens, CD/biosynthesis , Antigens, Neoplasm/biosynthesis , CD8-Positive T-Lymphocytes/pathology , Colonic Neoplasms/metabolism , Colonic Neoplasms/pathology , Female , Humans , Immunity, Mucosal/immunology , Integrin alpha Chains/biosynthesis , Lymphocyte Activation/immunology , Male , Middle Aged , Signal Transduction/immunology , Transforming Growth Factor beta1/immunology , Up-Regulation/immunology
10.
Dis Colon Rectum ; 49(12): 1837-41, 2006 Dec.
Article in English | MEDLINE | ID: mdl-17041753

ABSTRACT

INTRODUCTION: Infliximab is a monoclonal antibody against tumor necrosis factor-alpha, which has been shown to be effective in fistulating Crohn's disease. The safety of infliximab in patients with potential perianal sepsis is uncertain. This study was designed to assess the safety and outcome of infliximab therapy combined with surgery for patients with fistulating anal Crohn's disease. METHODS: All patients receiving infliximab for fistulating anal Crohn's disease between 2000 and 2004 were studied. Patients' demographics, clinical findings, magnetic resonance imaging, and examination under anesthesia were recorded. Perianal Crohn's disease activity index before and 8 to 12 weeks after three infusions of infliximab (5 mg/kg) were recorded. Routine policy was to insert drainage seton sutures at the time of preinfliximab examination under anesthesia and then remove it after the second infusion. Complications of treatment and outcome at the last clinic follow-up were recorded. RESULTS: Twenty-two patients underwent infliximab treatment (6 males; median age, 35 (range, 16-60) years). Twenty-one patients had preinfliximab examination under anesthesia: 12 required abscess drainage; 17 had at least one drainage seton suture inserted. Fourteen patients underwent pretreatment magnetic resonance imaging to identify clinically occult collections. All but one patient were established on immunomodulator therapy before infliximab treatment. Perianal Crohn's disease activity index improved significantly after infliximab infusion (preinfusion: median, 11, range, 8-17; postinfusion: median, 8, range, 5-16; P<0.001). There were no serious complications of infliximab treatment. At median follow-up of 21 (range, 4-31) months, only four patients achieved sustained fistula healing. Five patients have required defunctioning or proctectomy. Four patients have required repeated infusions of infliximab. CONCLUSIONS: Infliximab therapy in combination with examination under anesthesia/seton drainage is a safe and effective short-term treatment for fistulating anal Crohn's disease. Long-term fistula healing rates are low.


Subject(s)
Antibodies, Monoclonal/therapeutic use , Crohn Disease/therapy , Drainage , Gastrointestinal Agents/therapeutic use , Rectal Fistula/therapy , Adolescent , Adult , Crohn Disease/complications , Female , Follow-Up Studies , Humans , Infliximab , Male , Middle Aged , Prospective Studies , Rectal Fistula/etiology , Severity of Illness Index , Sutures , Treatment Outcome , Wound Healing
11.
Dis Colon Rectum ; 48(6): 1153-60, 2005 Jun.
Article in English | MEDLINE | ID: mdl-15868236

ABSTRACT

INTRODUCTION: Preoperative, long-course chemoradiotherapy is recommended for rectal cancers involving or threatening the mesorectal resection margin, but tumor response is variable. Some highly radiosensitive cancers completely regress, leading to reduced local recurrence and improved survival. This study was designed to evaluate the influence of anemia during chemoradiotherapy on tumor response, local and distant recurrence, and overall survival. METHODS: Mean hemoglobins during chemoradiotherapy of consecutive patients with rectal cancer undergoing chemoradiotherapy and surgery were calculated and ranked. Anemia was defined as lowest quartile for males and females. Tumor response was histologically quantified using rectal cancer regression grade. RESULTS: Of 100 patients, 5 females and 20 males were anemic. Nonanemic patients achieved better tumor response (54 percent regression Grade 1) than anemic patients (28 percent, P = 0.028). There were more locally advanced cancers in anemic (48 percent T4) compared with nonanemic patients (21 percent T4), but radiologic T stage did not influence tumor response (50 percent T3 vs. 43 percent T4 regression Grade 1, P = 0.53) or overall survival. Mesorectal margin positivity was less in nonanemic (15 percent) compared with anemic patients (36 percent, P = 0.021). At median follow-up of 39 months, nonanemic patients (7 percent) suffered less local recurrence than anemic patients did (38 percent, P = 0.003). Overall survival at two years was improved in nonanemic (91 percent) compared with anemic patients (64 percent, P = 0.021), but was similar for T3 and T4 patients. CONCLUSIONS: Patients with normal hemoglobin during chemoradiotherapy achieved better tumor response, less local recurrence, and improved overall survival compared with anemic patients, independent of radiologic T stage. Correcting anemia before chemoradiotherapy might improve tumor response and oncologic outcomes.


Subject(s)
Adenocarcinoma/complications , Adenocarcinoma/therapy , Anemia/complications , Neoadjuvant Therapy , Rectal Neoplasms/complications , Rectal Neoplasms/therapy , Adenocarcinoma/pathology , Adult , Aged , Aged, 80 and over , Cohort Studies , Female , Hemoglobins/metabolism , Humans , Male , Middle Aged , Neoplasm Recurrence, Local/prevention & control , Neoplasm Staging , Rectal Neoplasms/pathology , Retrospective Studies , Survival Rate , Treatment Outcome
12.
Dis Colon Rectum ; 48(2): 349-52, 2005 Feb.
Article in English | MEDLINE | ID: mdl-15812586

ABSTRACT

PURPOSE: Chronic anal fissure is said to be associated with internal sphincter hypertonia. However, an unknown proportion of fissures may be associated with normal or even low resting pressures and may subsequently be resistant to pharmacological treatments or at risk from surgical treatments, both of which aim to reduce sphincter hypertonia. This study investigated the ability of surgeons to detect low or normal pressure fissures by digital rectal examination. METHODS: Patients with chronic anal fissure were assessed prospectively. The results of anal manometry performed on these patients were compared with digital rectal assessment of sphincter tone undertaken by a surgeon blinded to the manometry results. RESULTS: Forty consecutive patients (21 male) with chronic anal fissure were studied. Twenty-two (55 percent) had normal maximum resting pressure and a further 3 (8 percent) had low pressures on anal manometry. On clinical assessment, only five (13 percent) patients were evaluated as having no anal hypertonia. Clinical assessment of anal tone correctly identified 14 of 15 patients with high manometric maximum resting pressure (sensitivity, 93 percent), yet detected only 4 of 25 patients with normal or low pressures (specificity, 16 percent). The positive predictive value of clinical assessment of anal tone was 40 percent and the negative predictive value, 80 percent. CONCLUSIONS: The incidence of patients with chronic anal fissure without high manometric maximum resting pressure is higher than previously reported. The ability of surgeons to identify this group clinically was poor. It is reasonable to treat all patients primarily medically, and then selectively investigate by manometry those patients who fail medical therapy before considering lateral sphincterotomy.


Subject(s)
Anal Canal/physiopathology , Fissure in Ano/physiopathology , Physical Examination , Chronic Disease , Female , Humans , Male , Manometry , Muscle Hypertonia/physiopathology , Prospective Studies , Reproducibility of Results , Statistics, Nonparametric
13.
Dis Colon Rectum ; 46(3): 361-6, 2003 Mar.
Article in English | MEDLINE | ID: mdl-12626912

ABSTRACT

PURPOSE: Glyceryl trinitrate paste is used by many as first-line therapy for chronic anal fissure but heals only approximately 50 to 60 percent of fissures. We use botulinum toxin as second-line therapy after failed glyceryl trinitrate and aimed to evaluate efficacy, side effects, and patient preference. METHODS: A prospective, nonrandomized, open-label study of patients with chronic anal fissure failing a course of glyceryl trinitrate treated with 20 units of botulinum toxin A injected into the internal sphincter was conducted. Symptomatic relief, visual healing of fissures, side effects, and patient preference were assessed at 8-week follow-up. RESULTS: Forty patients underwent botulinum toxin treatment. Twenty-nine patients (73 percent) overall were improved symptomatically and avoided surgery. Seventeen fissures (43 percent) were healed, whereas 23 fissures (57 percent) remained unhealed. Of the unhealed fissures, 5 (12 percent) were asymptomatic, 7 (18 percent) were symptomatically much improved, and 11 (27 percent) were no better symptomatically and came to surgery. Discomfort associated with injection was minimal. Of 34 patients undergoing botulinum toxin injection in the clinic, 24 (71 percent) preferred botulinum toxin, 7 glyceryl trinitrate (20 percent; difference = 51 percent; 95 percent confidence interval = 31-71 percent), and 9 percent were undecided. Transient minor incontinence symptoms were noted in 7 patients (18 percent). CONCLUSIONS: Second-line botulinum toxin injection improves symptoms in approximately three-quarters of patients after failed primary glyceryl trinitrate therapy and at least in the short term avoids surgical sphincterotomy. Botulinum toxin heals approximately one-half of these fissures. Discomfort and side effects were minimal. A policy of first-line glyceryl trinitrate/second-line botulinum toxin will avoid sphincterotomy in 85 to 90 percent. Higher rates of healing may be achieved by giving botulinum toxin as first-line therapy, or addressing the chronic fibrotic nature of the fissure.


Subject(s)
Botulinum Toxins/administration & dosage , Fissure in Ano/drug therapy , Wound Healing/drug effects , Adult , Aged , Aged, 80 and over , Anal Canal , Botulinum Toxins/adverse effects , Botulinum Toxins/therapeutic use , Chronic Disease , Female , Humans , Male , Middle Aged , Nitroglycerin/therapeutic use , Patient Satisfaction , Prospective Studies , Treatment Failure , Treatment Outcome , Vasodilator Agents/therapeutic use
14.
Dis Colon Rectum ; 46(1): 14-9, 2003 Jan.
Article in English | MEDLINE | ID: mdl-12544516

ABSTRACT

PURPOSE: We aimed to assess objectively the integrity of the parasympathetic neural pathway that controls the inflow choke vessels to the corpora cavernosa in a group of male patients with postproctectomy erectile dysfunction. METHODS: The study group was male patients with erectile dysfunction after proctectomy for rectal cancer and inflammatory bowel disease identified by sexual function questionnaire. The group underwent two consecutive nights of home nocturnal penile tumescence monitoring with the Nocturnal Electrobioimpedance Volumetric Assessment device. The control group was also monitored. It comprised preoperative potent patients with rectal cancer and inflammatory bowel disease who had not yet undergone a variety of surgical procedures. Demographics and nocturnal penile tumescence parameters were recorded, including number, duration, and percentage increase in penile volume of tumescent events. RESULTS: Thirty-four impotent study group and 28 potent control group patients underwent nocturnal penile tumescence monitoring. The groups were well matched for mean age (difference, 1.4 years; 95 percent confidence interval, -5.8 to 8.6 years) and proportion with rectal cancer (difference, 6 percent; 95 percent confidence interval, -1 to 13 percent). The number of nocturnal penile tumescent events was greater for the potent group than for the control group (mean rank, 40.4 vs. 24.2; P = 0.0004). There was no significant difference between the mean duration (difference, 2.6 minutes; mean rank, 27.9 vs. 34.4; P = 0.16) or the mean penile volume increase (difference, 5.4 percent increase; mean rank, 30.6 vs. 32.6; P = 0.66) for tumescent events between the study and control groups. Mean age was significantly higher in complete than in partial impotence (60.9 vs. 53.1 years; difference, 7.8 years; 95 percent confidence interval, 0.1 to 15.5 years). There was a nonsignificant trend to a lower mean number of tumescence events among sildenafil responders than among nonresponders (3.5 vs. 4.8 events; mean rank, 11.2 vs. 17.3; P = 0.14). CONCLUSION: Nocturnal penile tumescence activity is diminished but not ablated by the trauma of surgical dissection. This suggests that some of the cavernous nerves that govern inflow to the corpora cavernosa are intact after surgery and that the nerve lesion responsible for erectile dysfunction is partial, and it explains why the response to sildenafil in such patients is surprisingly high.


Subject(s)
Erectile Dysfunction/etiology , Erectile Dysfunction/physiopathology , Inflammatory Bowel Diseases/surgery , Penis/blood supply , Penis/innervation , Rectal Neoplasms/surgery , Adult , Aged , Aged, 80 and over , Case-Control Studies , Electric Impedance , Humans , Male , Middle Aged , Monitoring, Physiologic , Piperazines/therapeutic use , Purines , Retrospective Studies , Severity of Illness Index , Sildenafil Citrate , Statistics, Nonparametric , Sulfones , Surveys and Questionnaires , Vasodilator Agents/therapeutic use
15.
Dis Colon Rectum ; 45(12): 1608-15, 2002 Dec.
Article in English | MEDLINE | ID: mdl-12473883

ABSTRACT

PURPOSE: Fibrin glue is a novel treatment for anal fistulas and possesses many advantages in the treatment of difficult high fistulas. Fibrin glue treatment is simple and repeatable; failure does not compromise further treatment options; and sphincter function is preserved. We aimed to compare the outcomes of patients with low and high anal fistulas randomly assigned to either fibrin glue or conventional treatment. METHODS: Patients with simple fistulas (low fistulas) and complex fistulas (high, Crohn's, and low fistulas with compromised sphincters) were randomly assigned to either fibrin glue or conventional treatment (fistulotomy or loose seton insertion with or without subsequent advancement flap). Patients with rectovaginal fistulas and anal fistulas associated with chronic cavities, acute sepsis, and side branches were excluded. The primary end point was fistula healing. Secondary end points were complications, changes in preoperative continence score, changes in maximum resting and squeeze pressure, satisfaction scores, and pain scores and time off work (simple fistulas only). RESULTS: Patients in the fibrin glue and conventional treatment arms were well matched for gender, median age, duration of fistula symptoms, and follow-up. Fibrin glue healed three (50 percent) of six and fistulotomy seven (100 percent) of seven simple fistulas (difference, 50 percent; confidence interval, 10 to 90 percent; P= 0.06, Fisher's exact probability test). There was no change in baseline incontinence score, maximum resting pressures, or squeeze pressures between the study arms. Return to work was quicker in the glue arm, but pain scores were similar and satisfaction scores higher in the fistulotomy group. Fibrin glue healed 9 (69 percent) of 13 and conventional treatment 2 (13 percent) of 16 complex fistulas (difference, 56 percent; 95 percent confidence interval, 25.9 to 86.1 percent; P= 0.003, Fisher's exact probability test). There was no change in baseline incontinence score, maximum resting pressures, or squeeze pressures in either study arm. Satisfaction scores were higher in the fibrin glue group. CONCLUSIONS: No advantage was found for fibrin glue over fistulotomy for simple fistulas, but fibrin glue healed more complex fistulas than conventional treatment and with higher patient satisfaction.


Subject(s)
Fibrin Tissue Adhesive/therapeutic use , Rectal Fistula/surgery , Rectal Fistula/therapy , Suture Techniques , Tissue Adhesives/therapeutic use , Adult , Aged , Female , Humans , Male , Middle Aged , Patient Satisfaction , Severity of Illness Index , Surgical Flaps , Treatment Outcome
16.
Dis Colon Rectum ; 45(3): 377-83, 2002 Mar.
Article in English | MEDLINE | ID: mdl-12068198

ABSTRACT

PURPOSE: We investigated the hypothesis that there is an "aggressive" subtype of Crohn's disease characterized by early recurrence and that disease location and surgical procedure are associated with differing patterns of recurrence. METHODS: We analyzed 280 patient records totaling 482 major abdominal operations from a prospectively compiled Crohn's disease database. Patterns of recurrence, as defined by reoperation, were analyzed by Kaplan-Meier plots and log-rank tests for the group as a whole, as well as according to disease location and operation performed using log-rank and Cox regression analysis. RESULTS: The overall survival curve followed a simple curve with no apparent early rise in recurrence. There was a significantly higher recurrence rate for ileal disease than for ileocolic or colic disease (median reoperation-free survival, 37.8 vs. 47.8 and 54.7 months, respectively; log-rank test = 13.6; P = 0.001), and there was a significantly shorter reoperation-free survival for those patients treated by strictureplasty alone or stricture-plasty combined with resection than for those treated by resection alone (41.7 and 48.6 vs. 51 months, respectively; log-rank test = 12; P = 0.002), but only disease site was confirmed as an independent risk factor for recurrence by multiple regression analysis. CONCLUSIONS: These data suggest that there is no evidence for the existence of a separate, early recurring, aggressive disease type. Shorter reoperation-free survival after strictureplasty may reflect patterns of recurrence in ileal disease.


Subject(s)
Colon/surgery , Crohn Disease/mortality , Crohn Disease/surgery , Digestive System Surgical Procedures , Ileum/surgery , Recurrence , Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Crohn Disease/etiology , Female , Humans , Male , Middle Aged , Prospective Studies , Reoperation , Risk Factors , Survival Rate , Time Factors
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