Background
Colorectal cancer leads to peritoneal metastases (CRPM) in 10% of cases. Cytoreductive surgery with hyperthermic intraperitoneal chemoperfusion (CRS-HIPEC) improves survival. Primary tumor ...location and abnormalities in
RAS
,
BRAF
, and mismatch repair/microsatellite stability (MMR/MSI) may affect post-CRS-HIPEC survival, but studies have not been consistent. We estimated the effects of primary tumor site and genomic alterations on post-CRS-HIPEC survival.
Methods
This retrospective cohort study included CRS-HIPEC cases for CRPM at a high-volume center from 2001 to 2020. Next-generation sequencing and microsatellite testing defined the
RAS
,
BRAF
, and MMR/MSI genotypes. Adjusted effects of tumor sidedness and genomics on survival were evaluated using a multivariable Cox proportional hazards model. We analyzed these variables’ effects on progression-free survival and the effects of immune checkpoint-inhibitors.
Results
A total of 250 patients underwent CRS-HIPEC with testing for
RAS
,
BRAF
, and MMR/MSI; 50.8% of patients were
RAS
-mutated, 12.4% were
BRAF
-mutated, and 6.8% were deficient-MMR/MSI-high (dMMR/MSI-H). Genomic alterations predominated in right-sided cancers. After adjustment for comorbidities and oncological and perioperative variables, rectal origin hazard ratio (HR) 1.9,
p
= 0.01,
RAS
mutation (HR 1.6,
p
= 0.01), and
BRAF
mutation (HR 1.7,
p
= 0.05) were associated with worse survival.
RAS
mutation was also associated with shorter progression-free survival (HR 1.6,
p
= 0.01 at 6 months post-operatively), and dMMR/MSI-H status was associated with superior survival (HR 0.3,
p
= 0.01 at 2 years). dMMR/MSI-H patients receiving immune checkpoint-inhibitors trended toward superior survival.
Conclusions
Rectal origin,
RAS
mutations, and
BRAF
mutations are each associated with poorer survival after CRS-HIPEC for CRPM. Patients with CRPM and dMMR/MSI-H status have superior survival. Further research should evaluate benefits of immune checkpoint-inhibitors in this subgroup.
Background
Normal carcinoembryonic antigen (CEA) levels (≤ 2.5 ng/ml) after resection of localized colorectal cancer or liver metastases are associated with improved survival, however, these trends ...are understudied for colorectal peritoneal metastases (CRPM).
Patients and Methods
We conducted a retrospective single-institution study of patients with CRPM undergoing cytoreductive surgery with hyperthermic intraperitoneal chemoperfusion (CRS/HIPEC) with and without neoadjuvant chemotherapy (NACT). CEA was measured before and after NACT and within 3 months after CRS/HIPEC.
Results
A total of 253 patients (mean age 55.3 years) with CRPM undergoing CRS/HIPEC had complete CEA data and 191 also underwent NACT with complete data. The median peritoneal carcinomatosis index score (PCI) of the overall cohort was 12 and 82.7% of patients had complete cytoreduction (CC0). In total, 64 (33.5%) patients had normal CEA levels after NACT with a median overall survival (OS) of 45.2 months compared with those with an elevated CEA (26.4 months,
p
= 0.004). Patients with normal CEA after NACT had a lower PCI found at the time of surgery than those with elevated CEA (10 versus 14,
p
< 0.001), 68 (26.9%) patients with an elevated preoperative CEA level experienced normalization after CRS/HIPEC, and 118 (46.6%) patients had elevated CEA after CRS/HIPEC. Patients who experienced normalization demonstrated similar OS to patients that had normal CEA levels pre- and post-surgery and improved OS compared with those with elevated postop CEA (median 41.9 versus 47 months versus 17.1 months, respectively,
p
< 0.001).
Conclusions
Normal CEA levels after NACT and/or CRS/HIPEC are associated with improved survival for patients with CRPM. Patients that normalize CEA levels after surgery have similar survival to those with normal preoperative levels.
Background
Appendiceal mucinous neoplasms (AMNs) with disseminated disease (pseudomyxoma peritonei) are heterogeneous tumors with variable clinicopathologic behavior. Despite the development of ...prognostic systems, objective biomarkers are needed to stratify patients. With the advent of next-generation sequencing (NGS), it remains unclear if molecular testing can improve the evaluation of disseminated AMN patients.
Methods
Targeted NGS was performed for 183 patients and correlated with clinicopathologic features to include American Joint Committee on Cancer/World Health Organization (AJCC/WHO) histologic grade, peritoneal cancer index (PCI), completeness of cytoreduction (CC) score, and overall survival (OS).
Results
Genomic alterations were identified for 179 (98%) disseminated AMNs. Excluding mitogen-activated protein kinase genes and
GNAS
due to their ubiquitous nature, collective genomic alterations in
TP53
,
SMAD4
,
CDKN2A
, and the mTOR genes were associated with older mean age, higher AJCC/WHO histologic grade, lymphovascular invasion, perineural invasion, regional lymph node metastasis, and lower mean PCI (
p
< 0.040). Patients harboring
TP53
,
SMAD4
,
ATM
,
CDKN2A
, and/or mTOR gene alterations were found to have lower OS rates of 55% at 5 years and 14% at 10 years, compared with 88% at 5 years and 88% at 10 years for patients without the aforementioned alterations (
p
< 0.001). Based on univariate and multivariate analyses, genomic alterations in
TP53
,
SMAD4
,
ATM
,
CDKN2A
, and/or the mTOR genes in disseminated AMNs were a negative prognostic factor for OS and independent of AJCC/WHO histologic grade, PCI, CC score, and hyperthermic intraperitoneal chemotherapy treatment (
p
= 0.006).
Conclusions
Targeted NGS improves the prognostic assessment of patients with disseminated AMNs and identifies patients who may require increased surveillance and/or aggressive management.
Soil ecosystems contain and support the greatest amount of biodiversity on the planet. A majority of this diversity is made up of microorganisms, most of which are beneficial for humans. However, ...some of these organisms are considered human pathogens. In light of the current severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) outbreak, one may ponder the origin of the next pandemic and if soil may represent a source of pathogens with pandemic potential. This review focuses on several bacterial, fungal, and viral pathogens that can result in human infection due to direct interaction with the soil. Moreover, the current status of knowledge regarding SARS-CoV-2 survival in and transmission from soil is reviewed.
Appropriately developed practice guidelines present statements of best practice based on a thorough evaluation of the evidence from published studies on the outcomes of treatments, which include the ...application of multiple methods for collecting and evaluating evidence for a wide range of clinical interventions and disciplines. However, the guidelines are neither infallible, nor a substitute for clinical judgment. While the guideline development process is a complex phenomenon, conflict of interest in guideline development and inappropriate methodologies must be avoided. It has been alleged that the guidelines by the American College of Occupational and Environmental Medicine (ACOEM) prevent injured workers from receiving the majority of medically necessary and appropriate interventional pain management services. An independent critical appraisal of both chapters of the ACOEM guidelines showed startling findings with a conclusion that these guidelines may not be applied in patient care as they scored below 30% in the majority of evaluations utilizing multiple standardized criteria.
To reassess the evidence synthesis for the ACOEM guidelines for the low back pain and chronic pain chapters utilizing an expanded methodology, which includes the criteria included in the ACOEM guidelines with the addition of omitted literature and application of appropriate criteria.
For reassessment, randomized trials were utilized as it was in the preparation of the guidelines. In this process, quality of evidence was assessed and recommendations were made based on grading recommendations of Guyatt et al. The level of evidence was determined utilizing the quality of evidence criteria developed by the U.S. Preventive Services Task Force (USPSTF), as well as the outdated quality of evidence criteria utilized by ACOEM in the guideline preparation. Methodologic quality of each individual article was assessed utilizing the Agency for Healthcare Research and Quality (AHRQ) methodologic assessment criteria for diagnostic interventions and Cochrane methodologic quality assessment criteria for therapeutic interventions.
The results of reassessment are vastly different from the conclusions derived by the ACOEM guidelines. The differences in strength of rating for the diagnosis of discogenic pain by provocation discography and facet joint pain by diagnostic facet joint nerve blocks is established with strong evidence. Therapeutic cervical and lumbar medial branch blocks and radiofrequency neurolysis, therapeutic thoracic medial branch blocks, cervical interlaminar epidural steroid injections, caudal epidural steroid injections, lumbar transforaminal epidural injections, percutaneous and endoscopic adhesiolysis, and spinal cord stimulation qualified for moderate to strong evidence. Additional insight is also provided for evidence rating for intradiscal electrothermal therapy (IDET), automated percutaneous disc decompression, and intrathecal implantables.
The reassessment and reevaluation of the low back and chronic pain chapters of the ACOEM guidelines present results that are vastly different from the published and proposed guidelines. Contrary to ACOEM's conclusions of insufficient evidence for most interventional techniques, the results illustrate moderate to strong evidence for most diagnostic and therapeutic interventional techniques.
Comprehensive, evidence-based guidelines for interventional techniques in the management of chronic spinal pain are described here to provide recommendations for clinicians.
To develop evidence-based ...clinical practice guidelines for interventional techniques in the diagnosis and treatment of chronic spinal pain.
Systematic assessment of the literature.
Strength of evidence was assessed by the U.S. Preventive Services Task Force (USPSTF) criteria utilizing 5 levels of evidence ranging from Level I to III with 3 subcategories in Level II.
Short-term pain relief was defined as relief lasting at least 6 months and long-term relief was defined as longer than 6 months, except for intradiscal therapies, mechanical disc decompression, spinal cord stimulation and intrathecal infusion systems, wherein up to one year relief was considered as short-term.
The indicated evidence for accuracy of diagnostic facet joint nerve blocks is Level I or II-1 in the diagnosis of lumbar, thoracic, and cervical facet joint pain. The evidence for lumbar and cervical provocation discography and sacroiliac joint injections is Level II-2, whereas it is Level II-3 for thoracic provocation discography. The indicated evidence for therapeutic interventions is Level I for caudal epidural steroid injections in managing disc herniation or radiculitis, and discogenic pain without disc herniation or radiculitis. The evidence is Level I or II-1 for percutaneous adhesiolysis in management of pain secondary to post-lumbar surgery syndrome. The evidence is Level II-1 or II-2 for therapeutic cervical, thoracic, and lumbar facet joint nerve blocks; for caudal epidural injections in managing pain of post-lumbar surgery syndrome, and lumbar spinal stenosis, for cervical interlaminar epidural injections in managing cervical pain (Level II-1); for lumbar transforaminal epidural injections; and spinal cord stimulation for post-lumbar surgery syndrome. The indicated evidence for intradiscal electrothermal therapy (IDET), mechanical disc decompression with automated percutaneous lumbar discectomy (APLD), and percutaneous lumbar laser discectomy (PLDD) is Level II-2.
The limitations of these guidelines include a continued paucity of the literature, lack of updates, and conflicts in preparation of systematic reviews and guidelines by various organizations.
The indicated evidence for diagnostic and therapeutic interventions is variable from Level I to III. These guidelines include the evaluation of evidence for diagnostic and therapeutic procedures in managing chronic spinal pain and recommendations for managing spinal pain. However, these guidelines do not constitute inflexible treatment recommendations. Further, these guidelines also do not represent "standard of care."
Clinical guidelines are defined as systematically developed statements to assist practitioner and patient decisions about appropriate health care for specific clinical circumstances. The clinical ...guideline industry has been erupting even faster than innovation in health care, constantly adding unhealthy perspectives with broad and complex mandates to health care interventions. Clinical guidelines are based on evidence-based medicine (EBM) and comparative effectiveness research (CER). Multiple issues related to the development of clinical guidelines are based on conflicts of interest, controversies, and limitations of the guideline process. Recently, the American Pain Society (APS) developed and published multiple guidelines in managing low back pain resulting in multiple publications. However, these guidelines have been questioned regarding their development process, their implementation, and their impact on various specialties.
To reassess the APS guidelines' evidence synthesis for low back pain diagnostic interventions using the same methodology utilized by the APS authors. The interventions examined were diagnostic techniques for managing low back pain of facet joint origin, discogenic origin, and sacroiliac joint origin.
A literature search by two authors was carried out utilizing appropriate databases from 1966 through July 2008. Methodologic quality assessment was also performed by at least 2 authors utilizing the same criteria applied in APS guidelines. The guideline reassessment process included the evaluation of individual studies and systematic reviews and the translation into practice recommendations.
Our reassessment of Chou et al's evaluation, utilizing Chou et al's criteria, showed good evidence for lumbar facet joint nerve blocks, fair evidence for lumbar provocation discography, and fair to poor evidence for sacroiliac joint blocks to diagnose sacroiliac joint pain. The reassessment illustrates that Chou et al have utilized multiple studies inappropriately and have excluded appropriate studies. Also, Chou et al failed to eliminate their bias in their study evaluations.
The reassessment, using appropriate methodology and including high quality studies, shows evidence that differs from published APS guidelines.
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