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Radiotherapy and Oncology : Journal of... Jun 2022To conduct a systematic review evaluating the impact of high dose rate (HDR) brachytherapy (BT) on the clinical outcomes and toxicities of patients with anal cancer. (Review)
Review
PURPOSE
To conduct a systematic review evaluating the impact of high dose rate (HDR) brachytherapy (BT) on the clinical outcomes and toxicities of patients with anal cancer.
METHODS AND MATERIALS
A search of Medline, Embase, and Cochrane Library databases was performed using search terms: "anal", "anal canal", "squamous", "adenocarcinoma", "cancer", "neoplasm", in combination with "brachytherapy", "high dose rate brachytherapy" or "HDR brachytherapy". Additional studies were identified after scanning references. Studies published in English with ≥10 patients were included.
RESULTS
Ten studies (n = 448) were included in this review. 321 patients were treated with curative intent external beam radiotherapy (EBRT), chemotherapy (CT) and HDRBT; of those, 312 and 9 received interstitial and intraluminal BT, respectively. Mean follow up was 39.9 months (range (R): 24-61 months). Complete response was noted between 80%-93% and local control ranged between 81%-88%. Mean rate of local failure was 12.3% (SD 3.6%, R: 8%-18%). Distant failure rate was reported between 2%-3% and metastasis free survival ranged between 82%-88%. Mean disease free survival and overall survival were 77.3% (SD 6.6%, R: 66%-100%) and 82.5% (SD 13.7%, R: 70%-87.7%). Acute toxicity was mostly grade 1/2 dermatitis, proctitis or cystitis; G3 or higher toxicity was reported only in 4 patients in 2 studies (dermatitis n = 3 and sphincter necrosis n = 1). Most common long term toxicities were incontinence (2.5%-9%) and proctitis (2.5%-19%); G3/4 toxicity ranged between 2.2%-7.1%. Mean sphincter preservation rate and colostomy free survival was 88.0% and 80.4%, respectively.
CONCLUSION
Pooled analysis in this review suggests excellent response, local control and survival with HDRBT in combination with EBRT and CT, with limited toxicity. Prospective well conducted trials are needed to further establish role of HDRBT management of anal cancer with future focus on development of international consensus on patient selection, dosimetric parameters, treatment sequencing as well as defining uniform outcome and toxicity assessment.
Topics: Anus Neoplasms; Brachytherapy; Dermatitis; Humans; Proctitis; Prospective Studies; Radiotherapy Dosage; Retrospective Studies
PubMed: 35381275
DOI: 10.1016/j.radonc.2022.03.019 -
Frontiers in Pediatrics 2021Ulcerative colitis (UC) is a disabling disease, characterized by chronic inflammation of the colon, with a rising prevalence worldwide in the pediatric age group.... (Review)
Review
Ulcerative colitis (UC) is a disabling disease, characterized by chronic inflammation of the colon, with a rising prevalence worldwide in the pediatric age group. Although UC presents in children with varying severity, disease extent, and comorbidities, initial treatment is essentially uniform, consisting of 5-aminosalicylate drugs with corticosteroid induction for those with moderately to severely active disease. With the advent of anti-tumor necrosis factor (TNF) biologic therapy and several new biologics and small-molecule drugs for UC, precision medicine approaches to treatment are needed to more rapidly achieve sustained remission, restore quality of life, normalize development, and limit exposure to toxic corticosteroids in children with UC. Here, we review available data on clinical, biochemical, histopathologic, and molecular predictors of treatment response in UC. We also address known predictors and special treatment considerations in specific relevant scenarios such as very-early-onset UC, acute severe UC, ileal pouch anal anastomosis, and UC with concomitant primary sclerosing cholangitis. The review concludes with a prediction of how machine learning will integrate multimodal patient data to bring precision medicine to the bedside of children with UC in the future.
PubMed: 33681110
DOI: 10.3389/fped.2021.634739 -
The American Journal of Case Reports Feb 2020BACKGROUND A 70-year-old African American man presented with fatigue, dizziness, generalized weakness, and considerable weight loss of over 20 pounds in 3 weeks....
BACKGROUND A 70-year-old African American man presented with fatigue, dizziness, generalized weakness, and considerable weight loss of over 20 pounds in 3 weeks. History-taking revealed he was positive for HIV, hepatitis C, and severe chronic condyloma acuminatum, which had been progressing for 16 years. Treatment and surgical intervention had been continuously postponed due to the patient's long-standing history of heroin abuse. CASE REPORT Physical exam and diagnostics showed evidence of sepsis. He was hypotensive, with lactic acidosis and significant leucocytosis, and had acute-on-chronic kidney disease. Urinalysis was positive for nitrites and leukocyte esterase; therefore, broad-spectrum antibiotics were initiated. Additional sources of sepsis were considered due to persistent leucocytosis despite appropriate antibiotic coverage. An MRI of the pelvis was done to evaluate for necrosis of fistulization from potential internal warts as a source of sepsis. The lesions extended from the inguinal areas bilaterally, covering the medial thighs, lower scrotal wall, and wall junction. It had infiltrated the perineum and the entire rectal area, including the gluteal cleft and anus. The patient was consulted by colorectal surgery, urology, and infectious disease services. CONCLUSIONS Surgical biopsies found that he had both low- and high-grade squamous intraepithelial neoplasia. There was no evidence of invasive carcinoma, which was a concern given his weight loss. Surgery devised a plan that included a diverting colostomy (allowing the infected anal area to heal), followed by resection of his giant condyloma, and re-anastomosing of the bowels to return him to a normal baseline anatomy. A favorable prognosis was expected.
Topics: Aged; Buschke-Lowenstein Tumor; Colostomy; Condylomata Acuminata; HIV; Hepatitis C; Heroin Dependence; Humans; Immunocompromised Host; Male; Rectal Neoplasms; Squamous Intraepithelial Lesions
PubMed: 32088723
DOI: 10.12659/AJCR.920516 -
Journal of Pharmaceutical Analysis Dec 2023Excessive -acetyl--benzoquinone imine (NAPQI) formation is a starting event that triggers oxidative stress and subsequent hepatocyte necrosis in acetaminophen (APAP)...
Excessive -acetyl--benzoquinone imine (NAPQI) formation is a starting event that triggers oxidative stress and subsequent hepatocyte necrosis in acetaminophen (APAP) overdose caused acute liver failure (ALF). glutathionylation is a reversible redox post-translational modification and a prospective mechanism of APAP hepatotoxicity. Glutaredoxin-1 (Glrx1), a glutathione-specific thioltransferase, is a primary enzyme to catalyze deglutathionylation. The objective of this study was to explored whether and how Glrx1 is associated with the development of ALF induced by APAP. The knockout mice () and liver-specific overexpression of () mice were produced and underwent APAP-induced ALF. Pirfenidone (PFD), a potential inducer of Glrx1, was administrated preceding APAP to assess its protective effects. Our results revealed that the hepatic total protein glutathionylation (PSSG) increased and the Glrx1 level reduced in mice after APAP toxicity. mice were more sensitive to APAP overdose, with higher oxidative stress and more toxic metabolites of APAP. This was attributed to Glrx1 deficiency increasing the total hepatic PSSG and the glutathionylation of cytochrome p450 3a11 (Cyp3a11), which likely increased the activity of Cyp3a11. Conversely, mice were defended against liver damage caused by APAP overdose by inhibiting the glutathionylation and activity of Cyp3a11, which reduced the toxic metabolites of APAP and oxidative stress. PFD precede administration upregulated Glrx1 expression and alleviated APAP-induced ALF by decreasing oxidative stress. We have identified the function of Glrx1 mediated PSSG in liver injury caused by APAP overdose. Increasing Glrx1 expression may be investigated for the medical treatment of APAP-caused hepatic injury.
PubMed: 38223455
DOI: 10.1016/j.jpha.2023.08.004 -
Journal of Clinical Laboratory Analysis Feb 2020MicroRNAs (miRNAs) can be used for early diagnosis of myocardial infarction. However, due to a lack of standardized operating procedures, their value for clinical...
BACKGROUND
MicroRNAs (miRNAs) can be used for early diagnosis of myocardial infarction. However, due to a lack of standardized operating procedures, their value for clinical application is low.
METHODS
Detection of plasma miRNAs was optimized by analyzing factors influencing miRNA variance and myocardial infarction risk scores during analysis (extraction, reverse transcription, and real-time PCR) and pre-analysis (dietary status, anticoagulants, storage conditions, and hemolysis).
RESULTS
Regarding variable factors during analysis, the centrifugal column method was superior to Trizol LS reagent when extracting miRNA from plasma. Recovery rate was highest with plasma volumes of 200 and 300 µL. During analysis, the main source of miRNA detection inaccuracy was derived from RNA extraction (mainly organic extraction), and not reverse transcription or PCR. MiRNA variance could be reduced by use of an internal reference. During analysis, 95% of risk score variation fluctuated within a range of 6.267. The variable factors pre-analysis mainly involved dietary status, anticoagulant selection, and storage conditions. Hemolysis positively correlated with miRNA levels, but there was no significant change in risk score after internal reference calibration.
CONCLUSION
Preliminary standardization for miRNA detection provides a reference for clinical blood testing of miRNAs.
Topics: Adult; Aged; Anticoagulants; Blood Specimen Collection; Fasting; Female; Hemolysis; Humans; Male; MicroRNAs; Middle Aged; Myocardial Infarction; Real-Time Polymerase Chain Reaction; Reproducibility of Results
PubMed: 31617231
DOI: 10.1002/jcla.23058 -
Analytical Cellular Pathology... 2021In addition to playing a pivotal role in cellular energetics and biosynthesis, mitochondrial components are key operators in the regulation of cell death. In addition to... (Review)
Review
In addition to playing a pivotal role in cellular energetics and biosynthesis, mitochondrial components are key operators in the regulation of cell death. In addition to apoptosis, necrosis is a highly relevant form of programmed liver cell death. Differential activation of specific forms of programmed cell death may not only affect the outcome of liver disease but may also provide new opportunities for therapeutic intervention. This review describes the role of mitochondria in cell death and the mechanism that leads to chronic liver hepatitis and liver cirrhosis. We focus on mitochondrial-driven apoptosis and current knowledge of necroptosis and discuss therapeutic strategies for targeting mitochondrial-mediated cell death in liver diseases.
Topics: Animals; Apoptosis; Humans; Liver Diseases; Mitochondria; Necroptosis
PubMed: 34804779
DOI: 10.1155/2021/8900122 -
Cureus Jan 2023Ulcerative colitis (UC) causes diffuse friability and superficial wall degeneration that is accompanied by bleeding. UC, now recognized as a global illness, affects... (Review)
Review
Ulcerative colitis (UC) causes diffuse friability and superficial wall degeneration that is accompanied by bleeding. UC, now recognized as a global illness, affects millions of people globally. The most effective treatment for UC is Ileal Pouch Anal Anastomosis (IPAA). Many medical experts and patients favor proctocolectomy with IPAA because it improves bowel function and allows feces to pass via the anus. Considering the most recent research, systematic reviews, statistical analysis, and recommendations, a selective literature search was carried out. The database used was PubMed. The current work provides a summary of surgical alternatives, results, and pre-and postoperative treatment for UC patients. In the course of their illness, about 30% of UC patients will need surgery. Due to its natural limitation to the colon and rectum, UC may mostly be treated surgically. The preferred surgical process is a restorative proctocolectomy with an IPAA. A 30% postoperative complication rate and a 0.1% death rate for this operation are both shown in large studies. One of the biggest things preventing UC from being successfully treated surgically is pouchitis. A long-run success rate of the pouch is >90% after 10 follow-ups, despite a significant surgical complication rate. For patients with UC to have the best possible outcome, extensive collaboration among the various specialties in the pre and postoperative context is crucial. In skilled centers, more than 90% of the total patients can eventually achieve a decent quality of life despite a 30% likelihood of early postoperative problems. UC patients may be cured with proctocolectomy, but there is a risk of morbidity that must be considered, especially in pediatric patients. As a result of advancements in our comprehension of the pathogenic mechanisms causing UC, new therapies have been proposed, the most significant change being the emergence of anti-tumor necrosis factor (TNF) medications.
PubMed: 36814731
DOI: 10.7759/cureus.34027 -
The American Journal of Gastroenterology Nov 2023There is minimal evidence regarding the comparative effectiveness of individual antibiotics in the treatment of pouchitis. We sought to evaluate the comparative...
INTRODUCTION
There is minimal evidence regarding the comparative effectiveness of individual antibiotics in the treatment of pouchitis. We sought to evaluate the comparative effectiveness of ciprofloxacin monotherapy, metronidazole monotherapy, and combination therapy (ciprofloxacin and metronidazole) in the treatment of an initial episode of pouchitis after ileal pouch-anal anastomosis for ulcerative colitis (UC).
METHODS
We performed a retrospective cohort study in TriNetX, a global federated research network of electronic health records. Primary outcomes were failure of initial antibiotic therapy and the development of recurrent pouchitis in the first 12 months after an initial episode of pouchitis. One-to-one propensity score matching was performed for age, sex, race, primary sclerosing cholangitis, nicotine dependence, obesity, and previous exposure to tumor necrosis factor inhibitors between the cohorts.
RESULTS
Among 271 patients who developed pouchitis (mean age at ileal pouch-anal anastomosis 35.8 years, male sex 57%) and were treated with ciprofloxacin, metronidazole, or combination therapy, 190 (70%) developed recurrent pouchitis. After propensity score matching, there was no significant difference in the odds of early relapse or nonresponse with ciprofloxacin compared with metronidazole monotherapy (adjusted odds ratio 0.56, 95% confidence interval 0.23-1.34) or when either monotherapy was compared with combination therapy. There was also no significant difference in odds of recurrent pouchitis when comparing patients treated with ciprofloxacin with metronidazole monotherapy (adjusted odds ratio 0.86, 95% confidence interval 0.40-1.84) or either monotherapy with combination therapy.
DISCUSSION
In this retrospective cohort study, we demonstrated no significant difference in the real-world effectiveness of ciprofloxacin, metronidazole, or combination therapy for the initial episode of pouchitis.
Topics: Humans; Male; Metronidazole; Ciprofloxacin; Pouchitis; Retrospective Studies; Anti-Bacterial Agents; Proctocolectomy, Restorative; Colitis, Ulcerative
PubMed: 37463438
DOI: 10.14309/ajg.0000000000002412 -
AJR. American Journal of Roentgenology May 2022Fistulizing perianal disease, a frequent, chronic, and often debilitating manifestation of Crohn disease (CD) in adults and children, has been relatively refractory to... (Review)
Review
Fistulizing perianal disease, a frequent, chronic, and often debilitating manifestation of Crohn disease (CD) in adults and children, has been relatively refractory to treatment in the past. The advent of biologic agents such as anti-tumor necrosis factor-α and cellular therapies, used in conjunction with a range of surgical interventions, has greatly improved disease outcomes, although complete remission can still be elusive. This Special Series review considers current perianal imaging options, specifically pelvic MRI and endoanal and transperineal ultrasound, as well as their roles in the diagnosis, management, and assessment of treatment response. Pelvic MRI is the first-line modality for imaging perianal CD, given the complexity of fistulas encountered in CD. MRI technical acquisition parameters for adults and children and an approach to MRI interpretation and reporting are provided. Anatomic classification systems for fistulizing peri-anal disease are presented. We also explore the history, current landscape, and future developments of MRI features of perianal disease as imaging biomarkers, to quantify activity and severity and to consider CD MRI-based inflammatory activity scores. We discuss the reliability and validation of a number of indexes (including the pediatric MRI-based perianal CD [PEMPAC] index, the MR novel index for fistula imaging in CD [MAGNIFI-CD], the Van Assche index, and the modified Van Assche index), their potential to quantify treatment response, and possible prognostic capabilities.
Topics: Adult; Child; Crohn Disease; Humans; Inflammation; Magnetic Resonance Imaging; Rectal Fistula; Reproducibility of Results
PubMed: 34549607
DOI: 10.2214/AJR.21.26615 -
Current Stem Cell Research & Therapy 2023Crohn's Disease (CD), which usually leads to anal fistulas among patients, is the most important inflammatory bowel disease that causes morbidity in many people around... (Review)
Review
Crohn's Disease (CD), which usually leads to anal fistulas among patients, is the most important inflammatory bowel disease that causes morbidity in many people around the world. This review article proposes using MSCs as a hopeful therapeutic strategy for CD and anal fistula treatment in both preclinical and clinical conditions. Finally, darvadstrocel, a cell-based medication to treat complex anal fistulas in adults, as the only European Medicines Agency (EMA)-approved product for the treatment of anal fistulas in CD is addressed. Although several common therapies, such as surgery and anti-tumor necrosis factor-alpha (TNF-α) drugs as well as a combination of these methods is used to improve this disease, however, due to the low effectiveness of these treatments, the use of new strategies with higher efficiency is still recommended. Cell therapy is among the new emerging therapeutic strategies that have attracted great attention from clinicians due to its unique capabilities. One of the most widely used cell sources administrated in cell therapy is mesenchymal stem cell (MSC). This review article will discuss preclinical and clinical studies about MSCs as a potent and promising therapeutic option in the treatment of CD and anal fistula.
Topics: Adult; Humans; Crohn Disease; Inflammatory Bowel Diseases; Mesenchymal Stem Cells; Cell- and Tissue-Based Therapy; Fistula
PubMed: 34530720
DOI: 10.2174/1574888X16666210916145717