Comparison of triamcinolone and methylprednisolone efficacy and steroid flare reaction rates after shoulder corticosteroid injection: a prospective interrupted time series study.

BACKGROUND: A corticosteroid flare reaction is a well-described phenomenon that causes significant pain and dysfunction. The paucity of literature impedes decision making regarding which corticosteroid to use for shoulder injection. The purpose of this study was to compare methylprednisolone acetate (MPA) and triamcinolone acetonide (TA) injections in the glenohumeral joint and/or subacromial space in terms of efficacy and the incidence of steroid flare reactions. METHODS: In this prospective, interrupted time series, parallel study, patients received injections in the glenohumeral joint and/or subacromial space. MPA and TA were used during 2 discrete 3-month periods. The injections consisted of 2 mL of lidocaine, 2 mL of bupivacaine, and 80 mg of either MPA or TA. Visual analog scale (VAS) pain scores were recorded immediately before injection; 1-7 days after injection; and 3, 6, and 12 months after injection. The primary outcome was the incidence of a steroid flare reaction, defined as a post-injection increase in the VAS score by ≥2 points. The secondary outcome was injection failure, defined as a post-injection VAS score greater than the baseline score or the need for another intervention. We used linear mixed models with a patient-level random intercept to identify the mean VAS score change for TA injections in the first week after injection. RESULTS: MPA or TA shoulder injections were administered in 421 patients; of these patients, 15 received bilateral-joint injections whereas 406 received a single-joint injection, for a total of 436 injections (209 MPA and 227 TA injections). Pain scores in the first week after injection were available for 193 MPA and 199 TA injections. Significantly more patients in the MPA cohort reported flare reactions compared with the TA cohort (22.8% vs. 4.0%, P < .001) during the first week after injection. In the first week after injection, the mean VAS score of patients receiving TA injections was 1.05 (95% confidence interval, 0.47-1.63) lower than that of patients receiving MPA injections when adjusted for age, sex, race, pain type, surgeon type, and injection site. At 3 months, surveys for 169 MPA and 172 TA injections were completed, with no significant difference in the rate of injection failure for MPA vs. TA (42.6% vs. 36.1%, P = .224). Treatment failure rates were significantly higher for MPA than for TA at 6 months (78.44% vs. 62.5%, P < .001) but not at 12 months (81.18% vs. 81.42%, P = .531.) CONCLUSION: TA injections resulted in a >5-fold reduction in steroid flare reactions, with statistically superior 6-month efficacy rates, compared with MPA injections. This study supports TA as a more viable corticosteroid option for shoulder injection.

Reliability Testing of the Mayo Elbow Performance Score in Post-operative Patients.

This study aimed to determine intra-observer and inter-observer reliability of the Mayo Elbow Performance Score (MEPS). Patients undergoing elbow surgery completed a MEPS questionnaire initially and another 2-3 weeks later. During the second interview, patients completed the Oxford Elbow Score (OES) for comparison. Intraclass correlation coefficients (ICC) and Pearson correlation coefficients (PCC) > 0.80 indicated substantial agreement. In 42 patients who had elbow surgery, the average MEPS score initially was 78 (range, 5-100, SD 22.4) and 77 (range, 5-100, SD 21.5) at second interview. The average normalized OES score was 79 (range, 17-100, SD 23.6). The ICC for MEPS scores at the two time points was 0.90, and the PCC between the MEPS and OES scores was 0.87, indicating substantial agreement. The MEPS has strong intra-observer reliability at different time points and strong inter-observer reliability when compared with the OES, validating the MEPS as an outcome measure of elbow surgery. (Journal of Surgical Orthopaedic Advances 31(4):229-232, 2022).

Oral versus topical calcium channel blockers for chronic anal fissure-a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Chemical sphincterotomy with pharmacological agents is recommended as first line therapy for chronic anal fissures (CAF). Calcium channel blockers (CCB) are associated with similar efficacy but fewer side effects compared to nitrates. However, the optimal formulation (oral versus topical) is unknown. We aimed to perform a systematic review and meta-analysis to compare the effectiveness of oral and topical CCB in the treatment of CAF. METHODS: PubMed and Embase online databases were searched for relevant articles. Two independent reviewers performed methodological assessment and data extraction. Random effects models were used to calculate pooled effect size estimates. A sensitivity analysis was also carried out. RESULTS: Four randomized controlled trials describing 279 patients (138 in oral, 141 in topical group) were examined. There was significant heterogeneity among studies. On random effects analysis, topical CCB were associated with a significantly lower rate of unhealed fissure (21.3% vs. 38.4%; OR = 2.65, 95% CI = 1.50 to 4.69, p = 0.0008) when compared to oral therapy. However, there were no significant differences in fissure recurrence (5.4% vs. 5.5%; OR = 1.01, 95% CI = 0.31 to 3.33, p = 0.98) or side effects (15.6% vs. 39.1%; OR = 4.54, 95% CI = 0.46 to 44.3, p = 0.19) between topical and oral CCB. On sensitivity analysis, having excluded the most heavily biased trial, topical CCB were associated with significantly fewer side effects compared to oral therapy (4.3% vs. 38.0%; OR = 13.16, 95% CI = 5.05 to 34.3, p < 0.00001). CONCLUSIONS: Topical CCB are associated with better healing and fewer side effects when compared to oral therapy but there is no difference in recurrence rates.

Completion Proctectomy for Crohn's Colitis: Lessons Learned.

Surgical management of Crohn's disease is reserved for patients refractory to medical therapy and those who develop complications alleviated by surgery. Surgical resection may be the most efficient way to restore health in patients with stricturing and or fistulizing disease of the terminal ileum / small bowel. However, decision-making in patients with Crohn's colitis is more difficult. The merits of segmental resection versus subtotal/total colectomy versus total proctocolectomy with end ileostomy are affected by a myriad of factors, including extent of colon involvement, the patient's age, and the patient's degree of desire to avoid an ileostomy. In patients undergoing a total proctocolectomy for Crohn's colitis, the anal canal should be removed. The following case highlights the potential difficulty that may arise when the anal canal is left in situ.

Screening of exosomal microRNAs from colorectal cancer cells.

BACKGROUND: Cells release extracellular membrane vesicles including microvesicles known as exosomes. Exosomes contain microRNAs (miRNAs) however the full range within colorectal cancer cell secreted exosomes is unknown. OBJECTIVE: To identify the full range of exosome encapsulated miRNAs secreted from 2 colorectal cancer cell lines and to investigate engineering of exosomes over-expressing miRNAs. METHODS: Exosomes were isolated from HCT-116 and HT-29 cell lines. RNA was extracted from exosomes and microRNA array performed. Cells were engineered to express miR-379 (HCT-116-379) or a non-targeting control (HCT-116-NTC) and functional effects were determined. Exosomes secreted by engineered cells were transferred to recipient cells and the impact examined. RESULTS: Microvesicles 40-100 nm in size secreted by cell lines were visualised and confirmed to express exosomal protein CD63. HT-29 exosomes contained 409 miRNAs, HCT-116 exosomes contained 393, and 338 were common to exosomes from both cell lines. Selected targets were validated. HCT-116-379 cells showed decreased proliferation (12-15% decrease, p < 0.001) and decreased migration (32-86% decrease, p < 0.001) compared to controls. HCT-116-379 exosomes were enriched for miR-379. Confocal microscopy visualised transfer of HCT-116-379 exosomes to recipient cells. CONCLUSIONS: Colorectal cancer cells secrete a large number of miRNAs within exosomes. miR-379 decreases cell proliferation and migration, and miR-379 enriched exosomes can be engineered.

The curative management of synchronous rectal and prostate cancer.

OBJECTIVE: Neoadjuvant "long-course" chemoradiation is considered a standard of care in locally advanced rectal cancer. In addition to prostatectomy, external beam radiotherapy and brachytherapy with or without androgen suppression (AS) are well established in prostate cancer management. A retrospective review of ten cases was completed to explore the feasibility and safety of applying these standards in patients with dual pathology. To our knowledge, this is the largest case series of synchronous rectal and prostate cancers treated with curative intent. METHODS: Eligible patients had synchronous histologically proven locally advanced rectal cancer (defined as cT3-4Nx; cTxN1-2) and non-metastatic prostate cancer (pelvic nodal disease permissible). Curative treatment was delivered to both sites simultaneously. Follow-up was as per institutional guidelines. Acute and late toxicities were reviewed, and a literature search performed. RESULTS: Pelvic external beam radiotherapy (RT) 45-50.4 Gy was delivered concurrent with 5-fluorouracil (5FU). Prostate total dose ranged from 70.0 to 79.2 Gy. No acute toxicities occurred, excluding AS-induced erectile dysfunction. Nine patients proceeded to surgery, and one was managed expectantly. Three relapsed with metastatic colorectal cancer, two with metastatic prostate cancer. Five patients have no evidence of recurrence, and four remain alive with metastatic disease. With a median follow-up of 2.2 years (range 1.2-6.3 years), two significant late toxicities occurred; G3 proctitis in a patient receiving palliative bevacizumab and a G3 anastomotic stricture precluding stoma reversal. CONCLUSION: Patients proceeding to synchronous radical treatment of both primary sites should receive 45-50.4 Gy pelvic RT with infusional 5FU. Prostate dose escalation should be given with due consideration to the potential impact of prostate cancer on patient survival, as increasing dose may result in significant late morbidity. Review of published series explores the possibility of prostate brachytherapy as an alternative method of boost delivery. Frequent use of bevacizumab in metastatic rectal cancer may compound late rectal morbidity in this cohort. ADVANCES IN KNOWLEDGE: To our knowledge, this is the largest case series of synchronous rectal and prostate cancers treated with curative intent. This article contributes to the understanding of how best to approach definitive treatment in these patients.

Early post-operative removal of urethral catheter in patients undergoing colorectal surgery with epidural analgesia ­ a prospective pilot clinical study.

BACKGROUND: Urethral catheter (UC) removal is often delayed following colorectal resection due to the perceived increased risk of post-operative urinary retention (POUR) in patients with post-operative epidural analgesia (POEA). We aimed to determine if UC removal at 48 h, irrespective of ongoing POEA use, altered the risk of POUR and other morbidities associated with urethral catheterisation and immobility. METHODS: We performed a prospective randomised controlled pilot clinical study. Eligible patients were randomised to an experimental arm, SG1 (UC removal 48 h post-operatively), or a control arm, SG2 (UC removed following cessation of POEA). Rates of POUR, urinary tract infection (UTI), pulmonary complications and surgical site infection (SSI) were recorded. Forty-four patients were recruited (SG1: n = 22; SG2: n = 22). RESULTS: No females developed POUR, while it occurred in three males (20%) in SG1 and 2 males (22.2%) in SG2. All patients who developed POUR had undergone rectal resection. Males in SG1 were not at significantly increased risk of POUR compared to those in SG2 (R.R 0.875, p = 1). No patient developed UTI post-operatively. The rate of pulmonary complications (SG1: n = 2; SG2: n = 3, p = 0.229) and SSI (SG1: n = 5; SG2: n = 2, p = 0.146) were similar between both study arms. DISCUSSION: Males undergoing rectal surgery appear to be at increased risk of developing POUR in the presence of epidural analgesia, independent of the timing of UC removal. CONCLUSIONS: All female patients undergoing colorectal resection and male patients undergoing colonic resection may have their urethral catheter removed at 48 h irrespective of use of POEA. CLINICAL TRIALS REGISTRATION NUMBER: NCT01508767 (http://www.clinicaltrials.gov).

Awareness and uptake of family screening in patients diagnosed with colorectal cancer at a young age.

Background. One-fifth of people who develop colorectal cancer (CRC) have a first-degree relative (FDR) also affected. There is a large disparity in guidelines for screening of relatives of patients with CRC. Herein we address awareness and uptake of family screening amongst patients diagnosed with CRC under age 60 and compare guidelines for screening. Study Design. Patients under age 60 who received surgical management for CRC between June 2009 and May 2012 were identified using pathology records and theatre logbooks. A telephone questionnaire was carried out to investigate family history and screening uptake among FDRs. Results. Of 317 patients surgically managed for CRC over the study period, 65 were under age 60 at diagnosis (8 deceased). The mean age was 51 (30-59). 66% had node positive disease. 25% had a family history of colorectal cancer in a FDR. While American and Canadian guidelines identified 100% of these patients as requiring screening, British guidelines advocated screening for only 40%. Of 324 FDRs, only 40.9% had been screened as a result of patient's diagnosis. Conclusions. Uptake of screening in FDRs of young patients with CRC is low. Increased education and uniformity of guidelines may improve screening uptake in this high-risk population.

The use of circulating microRNAs as diagnostic biomarkers in colorectal cancer.

BACKGROUND: Abnormal levels of microRNAs (miRNAs) have been found in the blood or its components in a number of different cancers including colorectal cancer. In addition to being abundant in circulation, miRNAs show remarkable stability in both plasma and serum making miRNAs ideal markers for early detection in colorectal cancer. Several miRNAs have been identified as potential circulating biomarkers although none have been incorporated into clinical practice. OBJECTIVE: To identify the most consistently dysregulated circulating miRNAs in colorectal cancer patients according to current literature and postulate reasons for heterogeneity in results. METHODS: A literature review was performed using the electronic databases PubMed, Embase and the Cochrane Library. RESULTS: The 6 circulating miRNAs most frequently found to be dysregulated in colorectal cancer are miR-18a-5p, miR-21-5p, miR-29a-5p, miR-92a-5p, miR-143-5p and miR-378-5p. There are, however, multiple studies with conflicting findings. Studies vary significantly in ethnicity of populations, use of endogenous controls, source of miRNAs (whole blood, serum and plasma) and methods of detection. CONCLUSIONS: Circulating miRNAs are promising diagnostic biomarkers in colorectal cancer. Further studies identifying the source of tumour derived miRNAs in circulation, including identification of exosomal miRNA content, are required. Identifying pre-profiling factors affecting miRNA expression and determining stable endogenous controls will expedite the incorporation of miRNAs into clinical practice.

An unusual ischiorectal fossa mass.

INTRODUCTION: Peri-anal fistulae commonly present with collections requiring surgical intervention. The most common cause of a peri-anal mass is abscess formation secondary to anal gland sepsis. In certain patient groups such as those over 65 or with atypical presenting symptoms there are other important considerations. PRESENTATION OF CASE: A 70-year old male was referred by his general practitioner with symptoms of obstructed defaecation and a palpable mass in the ischiorectal fossa. He had previously undergone three operations for complex peri-anal fistulae in another hospital. Due to the previous history of surgery, seroma formation was considered and computed tomography guided drainage of the lesion was performed unsuccessfully. Given symptoms of obstructed defecation and need for histological diagnosis excision was undertaken. The approach was through a right pararectal incision over the bulk of the mass. Skin and pararectal tissue were divided revealing a mucinous lesion with multiple lobules adherent to pararectal tissue. Following histopathological examination a diagnosis of low grade mucinous neoplasm was made. DISCUSSION: Primary mucinous neoplasm in the ischiorectal fossa is very rare. Diagnostic criteria for adenocarcinoma arising from perianal fistulae have previously been established by Rosser et al. but this lesion does not fall into this category. It is categorised as a mucinous cystic neoplasm of uncertain malignant potential. The differential diagnoses are discussed. CONCLUSION: Consideration should be given to a range of pathologies in cases of atypical peri-anal masses.

Early recurrence and progression of a rare rectal squamous cell carcinoma after initial response to primary chemoradiotherapy.

Rectal squamous cell carcinomas represent an extremely rare malignancy which carries a significant morbidity and mortality. Diagnosis requires distinction from squamous cell carcinoma of the anus and colonic adenocarcinoma by endoscopy and histopathological examination of a biopsy. Due to the rarity of the pathology, available evidence is limited and optimum management has yet to be elucidated. Older reports favored radical surgical management, but recent reports in the literature recommend judicious use of primary chemoradiotherapy. We herein report the diagnosis and management of a male patient with an aggressive, locally advanced rectal squamous cell carcinoma treated with good results with primary chemoradiotherapy. Six months after completion of therapy, however, extensive recurrence and metastases were diagnosed. This case highlights the need for stringent clinical and radiological follow-up.

Impact of mesenchymal stem cell secreted PAI-1 on colon cancer cell migration and proliferation.

Mesenchymal Stem Cells are known to engraft and integrate into the architecture of colorectal tumours, with little known regarding their fate following engraftment. This study aimed to investigate mediators of Mesenchymal Stem Cell (MSC) and colon cancer cell (CCC) interactions. Mesenchymal Stem Cells and colon cancer cells (HT29 and HCT-116) were cultured individually or in co-culture on 3-dimensional scaffolds. Conditioned media containing all secreted factors was harvested at day 1, 3 and 7. Chemokine secretion and expression were analyzed by Chemi-array, ELISA (Macrophage migration inhibitory factor (MIF), plasminogen activator inhibitor type 1 (PAI-1)) and RQ-PCR. Colon cancer cell migration and proliferation in response to recombinant PAI-1, MSCs and MSCs+antibody to PAI-1 was analyzed using Transwell inserts and an MTS proliferation assay respectively. Chemi-array revealed secretion of a wide range of factors by each cell population, including PAI-1 and MIF. ELISA analysis revealed Mesenchymal Stem Cells to secrete the highest levels of PAI-1 (MSC mean 10.6 ng/mL, CCC mean 1.01 ng/mL), while colon cancer cells were the principal source of MIF. MSC-secreted PAI-1 stimulated significant migration of both CCC lines, with an antibody to the chemokine shown to block this effect (67-88% blocking,). A cell-line dependant effect on CCC proliferation was shown for Mesenchymal Stem Cell-secreted PAI-1 with HCT-116 cells showing decreased proliferation at all concentrations, and HT29 cells showing increased proliferation in the presence of higher PAI-1 levels. This is the first study to identify PAI-1 as an important mediator of Mesenchymal Stem Cell/colon cancer cell interactions and highlights the significant functional impact of Mesenchymal Stem Cell-secreted PAI-1 on colon cancer cells.

Smoking and Crohn's disease: active modification of an independent risk factor (education alone is not enough).

INTRODUCTION: Smoking can induce the onset of Crohn's disease in genetically susceptible patients and may accelerate progression and disease severity. There is a paucity of information as to patient knowledge of the impact of smoking on disease progression. The aim of this study was to assess patient awareness, initiate smoking cessation therapy and monitor the effectiveness of an active smoking cessation programme in patients with Crohn's disease. METHODS: All patients with a diagnosis of Crohn's disease over a ten year period were identified from a prospectively managed database. Details of smoking history and patient knowledge of the link between Crohn's disease and smoking were collected through a telephone questionnaire. Current smokers who wished to quit were enrolled in a smoking cessation programme and followed prospectively for 12 months. RESULTS: 340 patients were identified with 281 eligible for inclusion. 181 patients agreed to a telephone survey (64.4% patient uptake). Smokers had an increased incidence of surgical intervention (OR 2.2; CI 1.02, 4.78 P=0.043). Awareness of the link between smoking and Crohn's disease was highest in the current smoking cohort and lowest in the non-smoking cohort (CS:NS; 79.5%:43% p<0.001). 29% of patients with a smoking history had previously been offered smoking cessation therapy. 77% of current smokers opted for smoking cessation therapy. At 6 months 53% of these patients remained smoke free and 37% at 12 months. CONCLUSION: In patients with Crohn's disease, information alone is ineffective at achieving smoking cessation. Good cessation rates are achievable if information is supported by active smoking cessation therapy.

Impact of smoking on disease phenotype and postoperative outcomes for Crohn's disease patients undergoing surgery.

AIM: Whether smoking affects disease distribution, phenotype, and perioperative outcomes for Crohn's disease (CD) patients undergoing surgery is not well characterized. The aim of this study is to evaluate the impact of smoking on disease phenotype and postoperative outcomes for CD patients undergoing surgery METHODS: Prospectively collected data of CD patients undergoing colorectal resection were evaluated. CD patients who were current smokers (CS) were compared to nonsmokers (NS) and ex-smokers (ES) for disease phenotype, anatomic site involved, procedures performed, postoperative outcomes, and quality of life using the Cleveland Global Quality of Life instrument (CGQL). RESULTS: Of 691 patients with a diagnosis of CD requiring surgery 314 were classified as CS, 330 as NS, and 47 as ES. CS and ES in comparison to NS were significantly older at diagnosis of Crohn's disease (mean, 29.3 vs. 29.2 vs. 26.3 years) (P = 0.001) and older at the time of primary surgery (mean, 42.9 vs. 48.4 vs. 39 years) (P = 0.001) with a greater frequency of diabetes. In all groups requiring surgery, there was a significant change in disease phenotype from the time of diagnosis to surgical intervention. The predominant phenotype at diagnosis was inflammatory which changed to stricturing and penetrating as the dominant phenotypes at time of surgery. All groups had a significant improvement in CGQL scores post-surgery with the greatest benefit observed in NS. Postoperative complications and 30-day readmission rates were similar between all groups. CONCLUSIONS: The findings of this study show that in patients with CD, disease phenotype changes over time. This occurs independent of smoking. Smoking does not appear to predispose to complications for CD patients undergoing surgery. CS and ES have a persistently reduced quality of life in comparison to NS post-surgery.

Heterotopic ossification of the abdominal wall.

INTRODUCTION: Heterotopic ossification is a rare, benign condition which occurs when bone develops in tissues that do not normally ossify. PRESENTATION OF CASE: We herein report the case of a 73-year-old gentleman who underwent a laparotomy for a large splenic flexure tumour considered unresectable at initial intervention. Following delivery of chemotherapy, he was referred for a second opinion and the tumour with adjacent structures was removed at a subsequent laparotomy. A segment of abnormal hard tissue present in the abdominal wall was also excised. Histopathology revealed metaplastic bone deposition. DISCUSSION: Heterotopic ossification may occur at various sites and is a recognised but exceedingly infrequent sequela of abdominal surgery. CONCLUSION: This case highlights clinical, aetiological and histopathological features of this rare finding.

Surgical management of locally recurrent rectal cancer.

Developments in chemotherapeutic strategies and surgical technique have led to improved loco regional control of rectal cancer and a decrease in recurrence rates over time. However, locally recurrent rectal cancer continues to present considerable technical challenges and results in significant morbidity and mortality. Surgery remains the only therapy with curative potential. Despite a hostile intra-operative environment, with meticulous pre-operative planning and judicious patient selection, safe surgery is feasible. The potential benefit of new techniques such as intra-operative radiotherapy and high intensity focussed ultrasonography has yet to be thoroughly investigated. The future lies in identification of predictors of recurrence, development of schematic clinical algorithms to allow standardised surgical technique and further research into genotyping platforms to allow individualisation of therapy. This review highlights important aspects of pre-operative planning, intra-operative tips and future strategies, focussing on a multimodal multidisciplinary approach.

Mesenchymal stem cells in the colorectal tumor microenvironment: recent progress and implications.

Mesenchymal stem cells (MSCs) are nonhematopoietic multipotent adult stem cells. They have been shown to have a natural tropism for many tumors types, including colorectal, and are capable of escaping host immune surveillance. MSCs are known to engraft at tumors and integrate into their architecture, potentially as carcinoma-associated fibroblasts. In contrast with other malignancies, our understanding of the interactions between colorectal cancer cells and MSCs remains limited. Considering the established importance of inflammation in the colorectal cancer primary tumor microenvironment and the role of stromal cells in this process, there is a potential wealth of information to be gleaned from further investigation of interactions between these cell populations. Epithelial-mesenchymal transition is central to colorectal cancer progression and MSCs have also been implicated in this process. This review explores the current knowledge (both in vitro and in vivo) of interactions between colorectal cancer cells and MSCs. It highlights potential effects of cell source, number and ratio on outcome of in vivo studies and explores strategies to more accurately explore their role in the primary tumor microenvironment. As our understanding of the underlying molecular processes in colorectal cancer develops, elucidation of these interactions will be central to development of novel therapeutic strategies for this prevalent disease.