Non-operative management of rectal cancer: understanding tumor biology.
Ontology highlight
ABSTRACT:
SUBMITTER: Wei IH
PROVIDER: S-EPMC6252165 | biostudies-literature | 2018 Dec
REPOSITORIES: biostudies-literature
Publications
Non-operative management of rectal cancer: understanding tumor biology.
Wei Iris H IH Garcia-Aguilar Julio J
Minerva chirurgica 20180524 6
The management of locally-advanced rectal cancer involves a combination of chemotherapy, chemoradiation, and surgical resection to provide excellent local tumor control and overall survival. However, aspects of this multimodality approach are associated with significant morbidity and long-term sequelae. In addition, there is growing evidence that patients with a clinical complete response to chemotherapy and chemoradiation treatments may be safely offered initial non-operative management in a ri ...[more]
Similar Datasets
Project description:Despite advances in technique, surgical resection of rectal cancer remains a morbid procedure that can lead a profound decrease in a patient's quality of life. A novel method of management, termed "Non-operative management" (NOM), mirrors the management of anal carcinoma. Patients undergo definitive treatment with only chemotherapy and radiation, with resection reserved only for salvage. Current data is encouraging- both in reduction in morbidity and similar, if not superior oncologic results. However, there are a number of barriers to the wide adoption of this practice. This manuscript seeks to describe the rationale and execution of NOM as well as present the current data and pitfalls of the approach.
| S-EPMC7431003 | biostudies-literature
Project description:Colorectal cancer is the third most common cancer in men and the second most common in women worldwide, and the incidence is increasing among younger patients. 30% of these malignancies arise in the rectum. Patients with rectal cancer have historically been managed with preoperative radiation, followed by radical surgery, and adjuvant chemotherapy, with permanent colostomies in up to 20% of patients. Beginning in the early 2000s, non-operative management (NOM) of rectal cancer emerged as a viable alternative to radical surgery in select patients. Efforts have been ongoing to optimize neoadjuvant therapy for rectal cancer, thereby increasing the number of patients potentially eligible to forgo radical surgery. Magnetic resonance guided radiotherapy (MRgRT) has recently emerged as a treatment modality capable of intensifying preoperative radiation therapy for rectal cancer patients. This technology may also predict which patients will achieve a complete response to preoperative therapy, thereby allowing for more appropriate selection of patients for NOM. The present work seeks to illustrate the potential role MRgRT could play in personalizing rectal cancer treatment thus expanding the role of NOM in rectal cancer.
| S-EPMC7791447 | biostudies-literature
Project description:Despite it being the optimal curative approach, elderly and frail rectal cancer patients may not be able to undergo a total mesorectal excision. Frequently, no treatment is offered at all and the natural course of the disease is allowed to unfold. These patients are at risk for developing debilitating symptoms that impair quality of life and require palliative treatment. Recent advancements in non-operative treatment modalities have enhanced the toolbox of alternative treatment strategies in patients unable to undergo surgery. Therefore, a proposed strategy is to aim for the maximal non-operative treatment, in an effort to avoid the onset of debilitating symptoms, improve quality of life, and prolong survival. The complexity of treating elderly and frail patients requires a patient-centred approach to personalise treatment. The main challenge is to optimise the balance between local control of disease, patient preferences, and the burden of treatment. A comprehensive geriatric assessment is a crucial element within the multidisciplinary dialogue. Since limited knowledge is available on the optimal non-operative treatment strategy, these patients should be treated by dedicated multidisciplinary rectal cancer experts with special interest in the elderly and frail. The aim of this narrative review was to discuss a multidisciplinary patient-centred treatment approach and provide a practical suggestion of a successfully implemented clinical care pathway.
| S-EPMC9139821 | biostudies-literature
Project description:Background:The management of acute Achilles tendon ruptures is controversial, and most injuries are treated with surgery in the USA. The cost utility of operative versus non-operative treatment of acute Achilles tendon injury is unclear. Questions/Purposes:The purpose of this study was to compare the cost-effectiveness of operative versus functional non-operative treatment of acute Achilles tendon ruptures. Methods:A Markov cost-utility analysis was conducted from the societal perspective using a 2-year time horizon. Hospital costs were derived from New York State billing data, and physician and rehabilitation costs were derived from the Medicare physician fee schedule. Indirect costs of missed work were calculated using estimates from the US Bureau of Labor Statistics. Rates of re-rupture, major and minor complications, and the associated costs were obtained from the literature. Effectiveness was expressed in quality-adjusted life years (QALYs). For the base-case analysis, operative and non-operative patients were assumed to have the same utilities (quality of life) following surgery. Deterministic and probabilistic sensitivity analyses were conducted to evaluate the robustness of model assumptions. Results:In the base-case model, non-operative management of acute Achilles tendon ruptures dominated operative management, resulting in both lower costs and greater QALY gains. The differences in costs and effectiveness were relatively small. The benefit of non-operative treatment was 1.69 QALYs, and the benefit of operative treatment was 1.67 QALYs. Similarly, the total cost of operative and non-operative management was $13,936 versus $13,413, respectively. In sensitivity analyses, surgical costs and days of missed work were important drivers of cost-effectiveness. If hospitalization costs dropped below $2621 (compared with $3145) or the hourly wage rose above $29 (compared with $24), then operative treatment became a cost-effective strategy at the willingness-to-pay threshold of $50,000/QALY. The model results were also highly sensitive to the relative utilities for operative versus non-operative treatment. If non-operative utilities decreased relative to operative utilities by just 2%, then operative management became the dominant treatment strategy. Conclusion:For acute Achilles tendon ruptures, non-operative treatment provided greater benefits and lower costs than operative management in the base case; however, surgical costs and the economic impact associated with return to work are important determinants of the preferred cost-effective strategy.
| S-EPMC6974171 | biostudies-literature
Project description:BackgroundA trial of initial non-operative management is recommended in stable patients with adhesional small bowel obstruction. However, recent retrospective studies have suggested that early operative management may be of benefit in reducing subsequent recurrences. This study aimed to compare recurrence rates and survival in patients with adhesional small bowel obstruction treated operatively or non-operatively.MethodsThis was a prospective cohort study conducted at six acute hospitals in Denmark, including consecutive patients admitted with adhesional small bowel obstruction over a 4-month interval. Patients were stratified into two groups according to their treatment (operative versus non-operative) and followed up for 1 year after their index admission. Primary outcomes were recurrence of small bowel obstruction and overall survival within 1 year of index admission.ResultsA total of 201 patients were included, 118 (58.7 per cent) of whom were treated operatively during their index admission. Patients undergoing operative treatment had significantly better 1-year recurrence-free survival compared with patients managed non-operatively (operative 92.5 per cent versus non-operative 66.6 per cent, P <0.001). However, when the length of index admission was taken into account, patients treated non-operatively spent significantly less time admitted to hospital in the first year (median 3 days non-operative versus 6 days operative, P <0.001). On multivariable analysis, operative treatment was associated with decreased risks of recurrence (HR 0.22 (95 per cent c.i. 0.10-0.48), P <0.001) but an increased all-cause mortality rate (HR 2.48 (95 per cent c.i. 1.13-5.46), P = 0.024).ConclusionOperative treatment of adhesional small bowel obstruction is associated with reduced risks of recurrence but increased risk of death in the first year after admission.Registration numberNCT04750811 (http://www.clinicaltrials.gov).prior (registration date: 11 February 2021).
| S-EPMC10576245 | biostudies-literature
Project description:BackgroundPoorly managed post-operative pain can lead to complications and prolonged rehabilitation. Pain Management after ano-rectal surgery becomes important as it could hamper day to day activities, disturb sleep, alter appetite and bowel evacuations and decrease the quality of life. According to Acharya Sushrutha, pain (Shoola) cannot be produced without Vata dosha and Shoola (pain) is inevitable after Shastra (surgical) Karma (procedure) for which Basti (enema) is usually the management of choice. Rectal suppositories are one such dosage form that are extensively used in post-operative pain management especially after ano-rectal surgery.Materials and methodIn the study, a total of 40 patients who fulfilled the inclusion criteria were randomly divided to two groups comprising of 20 patients each. Patients of Group A were treated with Gandhaka Rasayana rectal suppository and Group B were treated with Diclofenac Sodium rectal suppository for post-operative 5 days.ResultsThe overall comparative results revealed a statistically significant improvement of 85% in Group A and 80.39% in Group B. Gandhaka Rasayana which is Tridoshashamaka, Vatamaya Nivaraka (ameliorates diseases caused by Vata dosha), Agnivardhaka (improves appetite and metabolism) and Shoolahara (reduces pain) attains micro particle size with 88 Bhavana (trituration) that can be readily absorbed by the rectal mucosa to exhibit the required therapeutic action.ConclusionThe Bhavana Dravya (medium of trituration) used in the preparation of Gandhaka Rasayana have proven analgesic, anti-inflammatory, anti-bacterial action and is also said to promote wound healing. The present study reveals that there is significant effect of Gandhaka Rasayana rectal suppositories in managing post-operative pain of ano-rectal disorders.
| S-EPMC9034460 | biostudies-literature
Project description:Rectal cancer treatment has undergone major changes over the last 15 years with a focus on individualized care based around MRI assessment of the relationship of the tumour to the mesorectal fascia, improved surgical techniques and targeted use of pre-operative oncological therapies in patients with locally advanced disease. The recognition that some tumours responded completely to pre-operative chemoradiotherapy, and the selective use of a non-operative policy has led to a quest to further identify those patients and their tumour in whom this approach could be used, irrespective of MRI stage. With no clear patient factors identified, the tumour and its gene expression has become a target for research to identify individual single-nucleotide polymorphisms, which may indicate a response to specific treatment, or not. To date some agents have been identified and trialed, such as cetuximab, with individual tumours being assessed for response allowing directed treatment. The reviewed paper by Sebio and colleagues report a study that links polymorphisms in the DNA repair gene XRCC1 with response to neoadjuvant 5-Fluorouracil treatment in rectal cancer patients. However, genetic heterogeneity alone may not explain the variations of drug response and environmental factors may lead to epigenetic effects and therefore alter responses. Therefore whilst this study demonstrates the impact of different single nucleotide polymorphisms (SNPs), it is only one step forward, but perhaps a step in the right direction.
| S-EPMC5233502 | biostudies-literature
Project description:OBJECTIVE:The aim of the study was to explore specific microRNAs (miRs) in rectal cancer that would predict response to radiation and identify target pathways that may be exploited for neoadjuvant therapies. SUMMARY BACKGROUND DATA:Chemoradiotherapy (CRT) response is a predictor of survival in rectal cancer. Studies have demonstrated changes in RNA expression correlate with chemoradiation sensitivity across cancers. METHODS:Forty-five rectal cancer patients, partial responders (PR = 18), nonresponders (NR = 13), and complete responders (CR = 14) to CRT, as defined by a tumor regression score, were examined. miRs differentially expressed, using NanoString microArray profiling, were validated with qPCR. We quantified 1 miR and its downstream targets in patient samples. Chemosensitivity was measured in HCT-116, a human colorectal carcinoma cell line, using inhibitors of SHP2 and RAF. RESULTS:miR-451a, 502-5p, 223-3p, and 1246 were the most upregulated miRs (>1.5-fold change) in a NanoString profiling miR panel. qPCR revealed a decrease in expression of miR-451a in NRs. EMSY and CAB39, both downstream targets of miR-451a and involved in carcinogenesis (shown in TCGA) were increased in NRs (qPCR). Both targets are associated with worse survival in colorectal cancer. Inhibition of miR-451a in HCT-116 cells significantly decreased cell proliferation with treatment of SHP2 and RAF inhibitors. CONCLUSIONS:An integrated analysis of rectal cancer miRs may yield biomarkers of radioresistance and offer treatment targets for resensitization.
| S-EPMC7289057 | biostudies-literature
Project description:IntroductionNon-operative management (NOM) of uncomplicated acute appendicitis is a well-established alternative to upfront surgery. The administration of intravenous broad-spectrum antibiotics is usually performed in hospital, and only one study described outpatient NOM. The aim of this multicentre retrospective non-inferiority study was to evaluate both safety and non-inferiority of outpatient compared to inpatient NOM in uncomplicated acute appendicitis.MethodsThe study included 668 consecutive patients with uncomplicated acute appendicitis. Patients were treated according to the surgeon's preference: 364 upfront appendectomy, 157 inpatient NOM (inNOM), and 147 outpatient NOM (outNOM). The primary endpoint was the 30-day appendectomy rate, with a non-inferiority limit of 5%. Secondary endpoints were negative appendectomy rate, 30-day unplanned emergency department (ED) visits, and length of stay.Results30-day appendectomies were 16 (10.9%) in the outNOM group and 23 (14.6%) in the inNOM group (p = 0.327). OutNOM was non-inferior to inNOM with a risk difference of-3.80% 97.5% CI (- 12.57; 4.97). No difference was found between inNOM and outNOM groups for the number of complicated appendicitis (3 vs. 5) and negative appendectomy (1 vs. 0). Twenty-six (17.7%) outNOM patients required an unplanned ED visit after a median of 1 (1-4) days. In the outNOM group, the mean cumulative in-hospital stay was 0.89 (1.94) days compared with 3.94 (2.17) days in the inNOM group (p < 0.001).ConclusionsOutpatient NOM was non-inferior to inpatient NOM with regard to the 30-day appendectomy rate, while a shorter hospital stay was found in the outNOM group. Further, studies are required to confirm these findings.
| S-EPMC10474178 | biostudies-literature
Project description:Fracture to fifth metatarsal's base is one the most common injury experienced at the foot. Studies have for long debated the use of operative and non-operative interventions for the management of the fracture, especially owing to its peculiar vasculature. However, to date, no attempt has been made to synthesize the evidence comparing the efficacy of operative and non-operative interventions for managing the fifth metatarsal's base fracture. To meta-statistically compare the effects of operative and non-operative management of fifth metatarsal base fracture. A systematic identification of literature was performed according to PRISMA guidelines on four academic databases: MEDLINE, Scopus, EMBASE, and CENTRAL. A meta-analysis evaluated the influence of operative and non-operative interventions on rate of non-union, mean duration of union, duration of return to activity, duration of return to sport, visual analog scale, and the American orthopedic foot & ankle scale. Out of 1,170 records, 11 articles including 404 participants (mean age: 29.8 ± 7.4 years) were included in this review. This systematic review presents a 1b level of evidence supporting the use of operative interventions for enhancing fracture union as compared to non-operative interventions. The meta-analysis reveals beneficial effects for operative interventions by demonstrating medium to large effect reduction of rate of non-union (Hedge's g: -0.66), duration of union (-1.7), duration of return to activity (-2.07), visual analog scale (-0.86), and enhancement of the American orthopedic foot & ankle scale score (0.73) as compared to non-operative intervention. The current systematic review and meta-analysis recommend the use of operative interventions for managing the fifth metatarsal's base fracture. The review reports beneficial effects of operative interventions as compared to non-operative interventions for reducing the rate of non-union, duration of union, duration of return to activity, duration of return to sport, visual analog scale, and increasing the American orthopedic foot & ankle scale score.
| S-EPMC7425975 | biostudies-literature