scholarly journals Effect of HIPEC on Peritoneal Recurrence in Peritoneal Metastasis Treated With Cytoreductive Surgery: A Systematic Review

2021 ◽  
Vol 11 ◽  
Author(s):  
Daniel Ren Yi Yap ◽  
Jolene Si Min Wong ◽  
Qiu Xuan Tan ◽  
Joey Wee-Shan Tan ◽  
Claramae Shulyn Chia ◽  
...  
Keyword(s):  
Systematic Review ◽  
Cytoreductive Surgery ◽  
Peritoneal Metastasis ◽  
Standard Of Care ◽  
Peritoneal Recurrence ◽  
Current Standard ◽  
Recurrence Rates ◽  
Treatment Regimens ◽  
Personalised Treatment ◽  
Different Origins

BackgroundPeritoneal metastasis (PM) is a late-stage manifestation of intra-abdominal malignancies. The current standard of care indicates that cure can only be achieved with cytoreductive surgery (CRS) which is often indicated with concurrent adjuvant hyperthermic intraperitoneal chemotherapy (HIPEC). However, the utility of HIPEC within subsets of PM is not fully understood. We seek to compare the effectiveness of HIPEC in improving peritoneal recurrence rates in PM of different origins.MethodsWe conducted a systematic review of trials on the PubMed, EMBASE, and Cochrane databases, last searched in August 2021. Biases were assessed using the Cochrane Collaboration’s tool for assessing the risk of bias in randomized trials as well as the Methodological Index for Non-Randomized Studies (MINORS) framework.Results7 gastric PM studies, 3 ovarian PM studies, and 3 colorectal PM studies were included. Recurrence-free survival was improved in the HIPEC + CRS cohort in 5 gastric trials but only 1 ovarian trial and none of colorectal origin.DiscussionOur findings indicate decent effectiveness of HIPEC in gastric PM, but limited utility in ovarian and colorectal PM. Limitations in the current literature are attributed to the paucity of data available, a lack of homogeneity and consideration of novel and personalised treatment regimens. We implore for further studies to be conducted with a focus on patient selection and stratification, and suggest a reframing of approach towards modern molecular and targeted therapeutic options in future studies of HIPEC.Systematic Review Registrationhttps://www.researchregistry.com/browse-the-registry#registryofsystematicreviewsmeta-analyses/registryofsystematicreviewsmeta-analysesdetails/60c1ffff0c1b78001e8efbe3/, identifier reviewregistry1166.

scholarly journals Cytoreductive Surgery Combined with Hyperthermic Intraperitoneal Chemotherapy for Peritoneal Metastasis from Colorectal Cancer

2020 ◽  
Vol 33 (06) ◽  
pp. 372-376
Author(s):  
Hideaki Yano
Keyword(s):  
Colorectal Cancer ◽  
Intraperitoneal Chemotherapy ◽  
Cytoreductive Surgery ◽  
Peritoneal Metastasis ◽  
Hyperthermic Intraperitoneal Chemotherapy ◽  
Peritoneal Cancer Index ◽  
Systemic Disease ◽  
Good Reason ◽  
Standard Of Care ◽  
Peritoneal Cancer

AbstractPeritoneal metastasis from colorectal cancer (PM-CRC) is used to be considered a systemic and fatal condition; however, it has been growingly accepted that PM-CRC can still be local disease rather than systemic disease as analogous to liver or lung metastasis.Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is now considered an optimal treatment for PM-CRC with accumulating evidence. There is a good reason that CRS + HIPEC, widely accepted as a standard of care for pseudomyxoma peritonei (PMP), could be a viable option for PM-CRC given a similarity between PM-CRC and PMP.Recent years have also seen that modern systemic chemotherapy with or without molecular targeted agents can be effective for PM-CRC. It is possible that neoadjuvant or adjuvant chemotherapy combined with CRS + HIPEC could further improve outcomes.Patient selection, utilizing modern images and increasingly laparoscopy, is crucial. Particularly, diagnostic laparoscopy is likely to play a significant role in predicting the likelihood of achieving complete cytoreduction and assessing the peritoneal cancer index score.

scholarly journals The Yin and the Yang of Treatment for Chronic Hepatitis B—When to Start, When to Stop Nucleos(t)ide Analogue Therapy

Viruses ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 934 ◽  
Author(s):  
Samuel Hall ◽  
Jessica Howell ◽  
Kumar Visvanathan ◽  
Alexander Thompson
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis B ◽  
Chronic Hepatitis B ◽  
Antiviral Agents ◽  
Standard Of Care ◽  
Current Standard ◽  
Hbsag Loss ◽  
Personalised Treatment ◽  
Treat All

Over 257 million individuals worldwide are chronically infected with the Hepatitis B Virus (HBV). Nucleos(t)ide analogues (NAs) are the first-line treatment option for most patients. Entecavir (ETV) and tenofovir disoproxil fumarate (TDF) are both potent, safe antiviral agents, have a high barrier to resistance, and are now off patent. They effectively suppress HBV replication to reduce the risk of cirrhosis, liver failure, and hepatocellular carcinoma (HCC). Treatment is continued long-term in most patients, as NA therapy rarely induces HBsAg loss or functional cure. Two diverging paradigms in the treatment of chronic hepatitis B have recently emerged. First, the public health focussed “treat-all” strategy, advocating for early and lifelong antiviral therapy to minimise the risk of HCC as well as the risk of HBV transmission. In LMICs, this strategy may be cost saving compared to monitoring off treatment. Second, the concept of “stopping” NA therapy in patients with HBeAg-negative disease after long-term viral suppression, a personalised treatment strategy aiming for long-term immune control and even HBsAg loss off treatment. In this manuscript, we will briefly review the current standard of care approach to the management of hepatitis B, before discussing emerging evidence to support both the “treat-all” strategy, as well as the “stop” strategy, and how they may both have a role in the management of patients with chronic hepatitis B.

Role for Thrombin Receptor Antagonism With Vorapaxar in Secondary Prevention of Atherothrombotic Events: From Bench to Bedside

2017 ◽  
Vol 23 (1) ◽  
pp. 23-37 ◽  
Author(s):  
Jae Youn Moon ◽  
Francesco Franchi ◽  
Fabiana Rollini ◽  
Dominick J. Angiolillo
Keyword(s):  
Platelet Activation ◽  
Standard Of Care ◽  
Current Standard ◽  
Recurrence Rates ◽  
Risk Patients ◽  
Thrombotic Complications ◽  
Artery Disease ◽  
Activation Pathways ◽  
The Impact ◽  
Ischemic Events

In spite of treatment with the current standard of care antiplatelet regimens including dual antiplatelet therapy, recurrence rates of ischemic events remain elevated for high-risk patients with atherosclerotic disease. This may be in part attributed to the fact that other key platelet activation pathways remain uninhibited and can thus continue to trigger platelet activation and lead to thrombotic complications. Thrombin is a powerful inducer of platelet activation and mediates its effects directly on platelets through protease activator receptors (PARs), particularly the PAR-1 subtype, making PAR-1 inhibition an attractive approach for reducing atherothrombotic events. These observations have led to the development of several PAR-1 antagonists. Vorapaxar is a direct inhibitor of PAR-1 and the only agent of this class approved for the prevention of recurrent ischemic events in patients with prior myocardial infarction or peripheral artery disease. In the present manuscript, we present a review of the pathophysiologic role of thrombin on thrombotic complications, the impact of vorapaxar on outcomes, including the most recent updates deriving from clinical trials, as well as future perspectives in the field.

scholarly journals Photodynamic therapy and photothermal therapy for the treatment of peritoneal metastasis: a systematic review

2018 ◽  
Vol 3 (4) ◽  
Author(s):  
Amandine Pinto ◽  
Marc Pocard
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Photodynamic Therapy ◽  
Cytoreductive Surgery ◽  
Peritoneal Metastasis ◽  
Photothermal Therapy ◽  
Bowel Perforation ◽  
Phase Iii ◽  
Preclinical Studies ◽  
Tumor Selectivity

AbstractBackgroundThe aim of this review was to analyze preclinical studies and clinical trials evaluating photodynamic therapy (PDT), and photothermal therapy (PTT) in peritoneal metastasis (PM) treatment.ContentSystematic review according PRISMA guidelines. Electronic searches using PubMed and Clinical Trials.SummaryA total of 19 preclinical studies analyzing PDT in PM treatment were included. Each new generations of photosensitizers (PS) permitted to improve tumoral targeting. Phase III preclinical studies showed an important tumoral biodistribution (ratio 9.6 vs normal tissue) and significant survival advantage (35.5 vs 52.5 days for cytoreductive surgery vs cytoreductive surgery+PDT, p<0.005). Height clinical trials showed important side effects (capillary leak syndrome and bowel perforation), mainly explained by low tumor-selectivity of the PS used (first generation mainly).Peritoneal mesothelioma apparition with carbon nanotubes first limited the development of PTT. But gold nanoparticles, with a good tolerance, permitted a limitation of tumoral growth (reduction of bioluminescence to 37 % 20 days after PTT), and survival benefit (35, 32, and 26 days for PTT with cisplatine, PTT alone and laser alone, respectively).OutlookRecent improvement in tumor-selectivity and light delivery systems is promising but further development would be necessary before PDT and PTT routinely applied for peritoneal carcinomatosis.

scholarly journals Stereotactic Body Radiotherapy for High-Risk Prostate Cancer: A Systematic Review

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 759
Author(s):  
Robert Foerster ◽  
Daniel Rudolf Zwahlen ◽  
Andre Buchali ◽  
Hongjian Tang ◽  
Christina Schroeder ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Systematic Review ◽  
High Risk ◽  
Stereotactic Body Radiotherapy ◽  
Selection Process ◽  
Oncological Outcome ◽  
Standard Of Care ◽  
Current Standard ◽  
High Risk Prostate Cancer ◽  
Gu Toxicity

Background: Radiotherapy (RT) is an established, potentially curative treatment option for all risk constellations of localized prostate cancer (PCA). Androgen deprivation therapy (ADT) and dose-escalated RT can further improve outcome in high-risk (HR) PCA. In recent years, shorter RT schedules based on hypofractionated RT have shown equal outcome. Stereotactic body radiotherapy (SBRT) is a highly conformal RT technique enabling ultra-hypofractionation which has been shown to be safe and efficient in patients with low- and intermediate-risk PCA. There is a paucity of data on the role of SBRT in HR PCA. In particular, the need for pelvic elective nodal irradiation (ENI) needs to be addressed. Therefore, we conducted a systematic review to analyze the available data on observed toxicities, ADT prescription practice, and oncological outcome to shed more light on the value of SBRT in HR PCA. Methods: We searched the PubMed and Embase electronic databases for the terms “prostate cancer” AND “stereotactic” AND “radiotherapy” in June 2020. We adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations. Results: After a rigorous selection process, we identified 18 individual studies meeting all selection criteria for further analyses. Five additional studies were included because their content was judged as relevant. Three trials have reported on prostate SBRT including pelvic nodes; 2 with ENI and 1 with positive pelvic nodes only. The remaining studies investigated SBRT of the prostate only. Grade 2+ acute genitourinary (GU) toxicity was between 12% and 46.7% in the studies investigating pelvic nodes irradiation and ranged from 0% to 89% in the prostate only studies. Grade 2+ chronic GU toxicity was between 7% and 60% vs. 2% and 56.7%. Acute gastrointestinal (GI) grade 2+ toxicity was between 0% to 4% and 0% to 18% for studies with and without pelvic nodes irradiation, respectively. Chronic GI grade 2+ toxicity rates were between 4% and 50.1% vs. 0% and 40%. SBRT of prostate and positive pelvic nodes only showed similar toxicity rates as SBRT for the prostate only. Among the trials that reported on ADT use, the majority of HR PCA patients underwent ADT for at least 2 months; mostly neoadjuvant and concurrent. Biochemical control rates ranged from 82% to 100% after 2 years and 56% to 100% after 3 years. Only a few studies reported longer follow-up data. Conclusion: At this point, SBRT with or without pelvic ENI cannot be considered the standard of care in HR PCA, due to missing level 1 evidence. Treatment may be offered to selected patients at specialized centers with access to high-precision RT. While concomitant ADT is the current standard of care, the necessary duration of ADT in combination with SBRT remains unclear. Ideally, all eligible patients should be enrolled in clinical trials.

scholarly journals Characterizing benefit from temozolomide in MGMT promoter unmethylated and methylated glioblastoma: a systematic review and meta-analysis

2020 ◽  
Vol 2 (1) ◽  
Author(s):  
Iyad Alnahhas ◽  
Mouaz Alsawas ◽  
Appaji Rayi ◽  
Joshua D Palmer ◽  
Raju Raval ◽  
...  
Keyword(s):  
Systematic Review ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Phase Iii ◽  
Current Standard ◽  
Prospective Data ◽  
Free Survival ◽  
Mgmt Promoter ◽  
Newly Diagnosed Glioblastoma

Abstract Background The current standard of care for the management of patients with newly diagnosed glioblastoma (GBM) includes maximal safe resection followed by radiotherapy (RT) with concurrent and adjuvant temozolomide (TMZ). While it is well established that TMZ has better efficacy in patients with MGMT promoter methylation, it remains an area of debate whether TMZ should be omitted when treating GBM patients with unmethylated MGMT. Methods We conducted a systematic review and meta-analysis to provide separate estimates of median overall survival (OS) and progression-free survival (PFS) for patients with methylated and unmethylated GBM treated with RT with or without TMZ. We searched multiple databases from inception to January 13, 2020. Results The median OS for patients with unmethylated GBM treated with RT/TMZ pooled from 5 phase III studies (N = 655) was 14.11 months (95% confidence interval [CI], 13.18–15.04) with a median PFS of 4.99 months (95% CI, 4.25–5.72). In contrast, the median OS for patients with methylated GBM pooled from 6 studies (N = 753) was 24.59 months (95% CI, 22.19–26.99) with a median PFS pooled from 7 studies (N = 805) of 9.51 months (95% CI, 7.41–11.61). There is a paucity of prospective data pertaining to OS/PFS in unmethylated patients treated with RT only and therefore a direct comparison was not possible. Conclusions This meta-analysis provides estimates of survival for patients with MGMT methylated or unmethylated GBM treated with RT/TMZ. Further research is needed to delineate whether TMZ should be withheld for patients with unmethylated GBM outside of the setting of clinical trials.

scholarly journals Baseline Characteristics and Current Standard of Care (SOC) Among US Veterans with Major Depressive Disorder (MDD)

CNS Spectrums ◽  
2021 ◽  
Vol 26 (2) ◽  
pp. 174-175
Author(s):  
Swapna Karkare ◽  
Abigail Nash ◽  
Eileen Han ◽  
John J. Sheehan ◽  
Aimee Near ◽  
...  
Keyword(s):  
Standard Of Care ◽  
Veterans Health ◽  
Health Administration ◽  
Post Traumatic Stress ◽  
Current Standard ◽  
Major Depressive ◽  
Treatment Regimens ◽  
Adequate Dose ◽  
Post Traumatic ◽  
Line Of Therapy

AbstractStudy ObjectivesTo describe characteristics of veterans with MDD and the different treatment regimens received during the first observed and treated major depressive episode (MDE).MethodsA retrospective study was performed using the Veterans Health Administration (VHA) database from 4/1/2015 to 2/28/2019 (study period), supplemented with Medicare Part A/B/D data from 4/1/2015 to 12/31/2017. Adult veterans with ≥1 MDD diagnosis in the VHA database between 10/1/2015 and 2/28/2017 (index date) were included if they received ≥1 line of therapy (LOT) within a complete MDE. An MDE was considered as starting on the date of the first observed MDD diagnosis preceded by ≥6 months depression-free period (i.e. a period without an MDD diagnosis or antidepressant (AD) use); an MDE was considered as ended on the date of the last MDD diagnosis or the end of the medication supply of the last AD/augmentation medication, whichever came last and then followed by ≥6 months depression-free period. An MDE was required to begin and end during the study period. A LOT was defined as ≥1 AD at adequate dose and duration (≥6 weeks of continuous therapy with no gaps longer than 14 days) with or without an augmenting medication. Patients were required to have VA benefit enrollment for ≥6 months before (baseline) and ≥24 months after index (follow-up). Patient baseline demographic and clinical characteristics as well as the number and type of LOTs (up to the first six LOTs) received during the first observed and treated MDE were evaluated.ResultsOverall, 40,240 veterans with MDD were identified (mean ± standard deviation [SD] age: 50.9±16.3 years).The majority were male (83.9%), White (63.4%), and non-Hispanic (88.6%); 60.1% were unemployed or retired at some point during the study period. The most commonly observed baseline comorbidities included hypertension (27.5%), hyperlipidemia (20.8%), post-traumatic stress disorder (17.5%), and diabetes (14.8%). During the first observed and treated MDE (mean ± SD duration: 14.7 ± 8.6 months), patients received a mean of 1.6±1.0 LOTs, with 36.5% and 14.6% of patients receiving ≥2 and ≥3 LOTs, respectively; 0.8% of patients received ≥6 LOTs. The most commonly observed therapies were SSRI monotherapy (58.9%) followed by SNRI monotherapy (8.8%) in LOT1; SSRI monotherapy followed by AD augmented with anticonvulsants in LOT2 (SSRI monotherapy: 48.7%; AD augmentation with anticonvulsants:12.1%) and LOT3 (SSRI monotherapy: 43.5%; AD augmentation with anticonvulsants:15.0%).ConclusionsThis study used an episodic approach to evaluate the current standard of care among veterans with MDD. During the first observed and treated MDE, about one in seven veterans received ≥3 LOTs, suggesting presence of treatment-resistant MDD. Monotherapy with SSRIs or SNRIs and combination therapies of AD with anticonvulsants were the most common therapies in the first three LOTs.FundingJanssen Scientific Affairs, LLC

Combination of Ceftriaxone and Ampicillin for the Treatment of Enterococcal Endocarditis: A Qualitative Systematic Review

2017 ◽  
Vol 51 (6) ◽  
pp. 496-503 ◽  
Author(s):  
Shaylee C. Peterson ◽  
Tim T. Y. Lau ◽  
Mary H. H. Ensom
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Case Reports ◽  
Data Extraction ◽  
Standard Of Care ◽  
Small Sample ◽  
Adverse Outcomes ◽  
World Health ◽  
Current Standard ◽  
Health Organization

Objective: The aim of this systematic review is to review all human trials assessing the efficacy and safety of ampicillin and ceftriaxone for enterococcal endocarditis and to discuss the clinical implications of the findings. Data Sources: MEDLINE (1946-), EMBASE (1974-), CENTRAL, Google Scholar, and the World Health Organization Clinical Trials Registry Platform were searched through January 2017 using the search terms ampicillin, penicillin, ceftriaxone, cephalosporin, enterococ*, and endocarditis. Unpublished studies were eligible for inclusion. Additional references were identified from literature citations. Study Selection and Data Extraction: Clinical trials in humans that reported on clinical efficacy or adverse outcomes with ceftriaxone and ampicillin therapy in patients with enterococcal endocarditis were included. Case reports, nonhuman, and non-English studies were excluded. Data Synthesis: Four observational clinical studies were identified. One examined the effects of ceftriaxone and ampicillin alone, and 3 compared the therapy to the current standard of care, ampicillin and gentamicin. The studies had small sample sizes and were not adequately designed or powered to establish noninferiority or equivalence to the current standard of care. Rates of clinical cure with ampicillin 2 g every 4 hours and ceftriaxone 2 g every 12 hours were similar to those of ampicillin and gentamicin. Ampicillin and ceftriaxone therapy was well tolerated with low rates of renal failure (0%-33%). Conclusion: The evidence to support the use of ampicillin and ceftriaxone for enterococcal endocarditis is not definitive. In the absence of compelling evidence, clinicians may consider ampicillin and ceftriaxone in patients with Enterococcus faecalis infection at high risk for nephrotoxicity or those with aminoglycoside-resistant pathogens.

scholarly journals Update on Chemotherapy in the Treatment of Urothelial Carcinoma

2011 ◽  
Vol 11 ◽  
pp. 1981-1994 ◽  
Author(s):  
Carrie Costantini ◽  
Frederick Millard
Keyword(s):  
Urothelial Carcinoma ◽  
Metastatic Disease ◽  
Standard Of Care ◽  
The United States ◽  
Concurrent Chemotherapy ◽  
Trial Participation ◽  
Current Standard ◽  
Bladder Preservation ◽  
Treatment Regimens ◽  
Carcinoma Of The Bladder

Urothelial carcinoma is the fifth most common malignancy diagnosed each year in the United States. Neoadjuvant and adjuvant chemotherapy are given to decrease the risk of recurrent or metastatic disease with the more robust clinical data supporting the former. Bladder preservation utilizes a trimodality approach with maximal transurethral resection followed by concurrent chemotherapy and radiation and is appropriate for select patients. Gemcitabine and cisplatin is the current standard of care for first-line treatment in fit patients with metastatic disease. Optimal second-line therapy remains undefined, and targeted agents are under investigation. Clinical trial participation should be encouraged in patients with urothelial carcinoma of the bladder to help improve treatment regimens and outcomes.Synopsis. Chemotherapy is commonly used in the treatment of urothelial carcinoma of the bladder. This paper will review the role of chemotherapy in the neoadjuvant, adjuvant, bladder sparing, and metastatic settings.

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