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Dermatologic Surgery : Official... Nov 2022Perineural invasion (PNI) is considered a high-risk histopathologic feature in many skin cancers. Perineural invasion is a well-known poor prognostic factor of squamous...
BACKGROUND
Perineural invasion (PNI) is considered a high-risk histopathologic feature in many skin cancers. Perineural invasion is a well-known poor prognostic factor of squamous cell carcinoma, but is poorly understood in the context of basal cell carcinoma (BCC).
OBJECTIVE
To analyze available demographic, clinical, and treatment data for BCC with PNI and the effect of these variables on recurrence patterns, disease progression, and cancer-specific mortality (CSM).
METHODS
A systematic review and pooled-survival analysis was performed using case reports and series of patients with perineural BCC.
RESULTS
This review included 159 patients from 49 publications. Of these cases, 57 patients reported at least one recurrence. Where reported, median follow-up time was 31 months for patients without recurrence ( n = 79) and 21 months for patients with recurrence ( n = 32). The cumulative incidence of CSM at 5 years was 8.5% (95% confidence interval [CI] 0.028-0.186) and the overall five-year survival was 90.9% (95% CI 0.796-0.961).
CONCLUSION
Male gender, multifocal nerve involvement, presence of clinical symptoms, and PNI detected on imaging are associated with poor prognosis of BCC with PNI. The high rate of disease recurrence and suboptimal cumulative incidence of CSM highlights the importance of early clinical detection, before the onset of symptomatic PNI and multifocal nerve involvement.
Topics: Humans; Male; Neoplasm Invasiveness; Neoplasm Recurrence, Local; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Survival Analysis; Prognosis; Peripheral Nerves; Retrospective Studies
PubMed: 36095258
DOI: 10.1097/DSS.0000000000003593 -
Skin Health and Disease Apr 2023Malignant Chondroid Syringomas (MCS) are very rare malignant tumours arising from cutaneous sweat glands, with only 51 reported cases in the literature. These tumours...
Malignant Chondroid Syringomas (MCS) are very rare malignant tumours arising from cutaneous sweat glands, with only 51 reported cases in the literature. These tumours can metastasize and cause death if not treated adequately. While there are histological criteria to diagnose MCS tumours, there are no established criterion to determine which tumours are more or less likely to metastasize. A systematic review was performed to establish if any features of the primary MCS tumour are associated with risk of metastasis or patient mortality, as well as the efficacy of common treatment options. The literature search was performed using the Ovid Medline and Web of Science databases from inception through March 2020. This yielded 47 case reports corresponding to 51 unique patients. Statistical analysis of the collected data revealed none of the commonly accepted malignant histopathologic findings (including nuclear atypia and/or pleomorphism, mitotic figures, an infiltrative growth pattern, presence of satellite nodules, necrosis, and vascular and/or perineural invasion) of the primary tumour to be significantly more associated with metastatic risk or death. However, gross characteristics of the tumour, including size (greater than 5 cm) and truncal location of the primary lesion, were found to be associated with a higher risk of metastasis. The most effective treatment modality was wide local excision. Overall, primary MCS tumours, especially those greater than 5 cm or located on the trunk, should be treated with a wide local excision and followed closely to confirm no lesion recurrence or distant metastasis.
PubMed: 37013126
DOI: 10.1002/ski2.144 -
Thyroid Research Jul 2022Sporadic medullary thyroid cancer accounts for 75% of all medullary thyroid cancers and presents at a more advanced disease stage than its hereditary counterparts. Yet... (Review)
Review
INTRODUCTION
Sporadic medullary thyroid cancer accounts for 75% of all medullary thyroid cancers and presents at a more advanced disease stage than its hereditary counterparts. Yet there is little evidence to support risk stratification of patients according to risk of recurrence.
METHODS
A systematic review and meta-analysis was performed investigating clinical and pathological factors that are associated with recurrent disease in patients with medullary thyroid cancer.
RESULTS
10 studies totalling 458 patients were included in the meta-analyses. T3 and T4 disease (OR 9.33 (95% CI 2.5 - 34.82) p = 0.0009.), AJCC stage III and IV disease (OR 13.34 (95% CI 2.9 - 60.3) p = 0.0008) and the presence of nodal disease (OR 7.28 (95% CI 7.2-43.3) p = 0.03) were all associated with recurrent disease. RET mutations (OR 0.08 (95% CI -0.03-0.19) p = 0.17) and RET 918 T mutations (OR 1.77 (95% CI 0.804.0) P = 0.17) were not associated with disease recurrence. It was not possible to pool data with respect to extrathyroidal extension, extracapsular extension, peri-neural and lymphovascular invasion and RAS mutations.
CONCLUSION
T3 and T4 disease, AJCC stage III and IV disease and the presence of nodal disease are associated with recurrent disease. The heterogeneous reporting of recurrence and the lack of individual patient data precludes larger scale meta-analyses. Future research in this area should involve collaboration to establish standardised definitions of disease recurrence.
PubMed: 35869537
DOI: 10.1186/s13044-022-00130-8 -
Oral Oncology Jul 2022At present, perineural invasion is used as a histologic indicator of aggressive salivary gland disease. In other head and neck malignancies, perineural invasion impacts... (Meta-Analysis)
Meta-Analysis
PURPOSE
At present, perineural invasion is used as a histologic indicator of aggressive salivary gland disease. In other head and neck malignancies, perineural invasion impacts staging of cancer lesions and therefore affects treatment options.
OBJECTIVE
To compare survival outcomes in primary parotid malignancies with and without perineural invasion.A systematic review pooled data from the scientific literature in patients with any primary parotid malignancy to investigate the prognosis of those with perineural invasion.
DATA SOURCES
PubMed (Medline), Scopus and Cochrane databases were queried from inception to July 2020 without any initial search constraints. Additional publications were included from review of pertinent articles.
STUDY SELECTION
Our inclusion criteria included primary parotid cancers with reported perineural invasion on survival outcomes. Exclusion criteria were non-English language text, non-human studies, reviews, textbooks, abstracts, case reports and case series. Two authors independently reviewed articles for inclusion. Of the initial 465 records, 83 articles were reviewed in full to yield a final collection of 14 studies.
DATA EXTRACTION AND SYNTHESIS
PRISMA-p guidelines were used in the reporting of our studies. A MOOSE Checklist was also used. MINORS criteria were applied to assess risk of bias. Random-effects models were used to estimate pooled effect sizes. No institutional review board review was needed for our study.
MAIN OUTCOMES AND MEASURES
Primary study outcomes were set prior to data collection and included overall survival (OS), disease-free survival (DFS), disease-specific survival (DSS) and distant-metastasis-free survival (DMFS) in patients with and without perineural invasion.
RESULTS
Fourteen studies contributed to this meta-analysis. Compared to patients without perineural invasion, the pooled rate of mortality (HR = 3.64), time to recurrence (HR = 3.56), disease-specific mortality (HR = 2.77) and distant metastasis (HR = 3.84) was significantly higher for patients with PNI (all p <.001). Controlling for perineural invasion status, no moderator was associated with these survival outcomes (all p >.05). Given the clinical severity of perineural invasion, few studies were null as shown in a panel of publication bias plots.
CONCLUSION
Perineural invasion portends a poor survival outcome in patients with parotid malignancies.
Topics: Disease-Free Survival; Humans; Neoplasm Invasiveness; Parotid Gland; Parotid Neoplasms; Prognosis
PubMed: 35662029
DOI: 10.1016/j.oraloncology.2022.105937 -
European Journal of Vascular and... Aug 2021Controlling pain after major lower limb amputation (MLLA) is of critical importance to patients and clinicians. The aim of this systematic review and meta-analysis was... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Controlling pain after major lower limb amputation (MLLA) is of critical importance to patients and clinicians. The aim of this systematic review and meta-analysis was to assess the effect of perineural catheters (PNCs) on post-operative pain, post-operative morphine requirement, in-hospital mortality, long term phantom limb pain, and chronic stump pain.
METHODS
A systematic review using PubMed, EMBASE via OVID and the Cochrane library from database inception (1946) to 20 October 2020 was performed according to PRISMA guidelines. Studies involving patients undergoing MLLA which reported on post-operative morphine requirement, pain scores, in-hospital mortality, phantom limb pain (PLP), and chronic stump pain were included. Studies comparing PNC use with epidural or wound site local anaesthetic infusions were excluded. Outcome data were extracted from individual studies and meta-analysis was performed using a random effects (Mantel-Haenszel) model for dichotomous data using an odds ratio (OR) summary statistic with 95% confidence intervals (CI), and with an inverse variance random effects model for continuous data using a standardised mean difference (SMD) summary statistic with 95% CIs. Sensitivity analyses were performed for post-operative pain scores and post-operative morphine requirement. Study quality was assessed using the Downs and Black score, and outcomes were assessed using the GRADE tool.
RESULTS
Ten studies reporting on 731 patients were included, with 350 patients receiving a PNC and 381 receiving standard care. PNC use is associated with a reduction in post-operative pain (SMD -0.30, 95% CI -0.58 - -0.01, p = .040, I = 54%, GRADE quality of evidence: low) and post-operative morphine requirements (SMD -0.63, 95% CI -1.03 - -0.23, p = .002, I = 75%, GRADE quality of evidence: moderate), although the effect of PNC on reduced post-operative morphine requirements is lost on sensitivity analysis of randomised trials only (p = .40). No demonstrable effect was found on in-hospital mortality, PLP, or chronic stump pain (GRADE quality of evidence: low).
CONCLUSION
PNC use in amputees is associated with a significant reduction in post-operative pain scores and post-operative morphine requirements, although this latter finding is lost on sensitivity analysis of randomised trials only.
Topics: Amputation, Surgical; Amputation Stumps; Analgesics, Opioid; Anesthetics, Local; Catheters; Hospital Mortality; Humans; Lower Extremity; Morphine; Pain Measurement; Pain, Postoperative; Peripheral Nerves; Phantom Limb
PubMed: 34088614
DOI: 10.1016/j.ejvs.2021.03.008 -
Neurobiology of Pain (Cambridge, Mass.) 2021Obesity has been associated with increased chronic pain susceptibility but causes are unclear. In this review, we systematize and analyze pain outcomes in rodent models... (Review)
Review
Obesity has been associated with increased chronic pain susceptibility but causes are unclear. In this review, we systematize and analyze pain outcomes in rodent models of obesity as these can be important tools for mechanistic studies. Studies were identified using MEDLINE/PubMed and Scopus databases using the following search query: (((pain) OR (nociception)) AND (obesity)) AND (rat OR (mouse) OR (rodent))). From each eligible record we extracted the following data: species, strain, sex, pain/obesity model and main behavioral readouts. Out of 695 records 33 were selected for inclusion. 27 studies assessed nociception/acute pain and 17 studies assessed subacute or chronic pain. Overall genetic and dietary models overlapped in pain-related outcomes. Most acute pain studies reported either decreased or unaltered responses to noxious painful stimuli. However, decreased thresholds to mechanical innocuous stimuli, i.e. allodynia, were frequently reported. In most studies using subacute and chronic pain models, namely of subcutaneous inflammation, arthritis and perineural inflammation, decreased thresholds and/or prolonged pain manifestations were reported in obesity models. Strain comparisons and longitudinal observations indicate that genetic factors and the time course of the pathology might account for some of the discrepancies observed across studies. Two studies reported increased pain in animals subjected to high fat diet in the absence of weight gain. Pain-related outcomes in experimental models and clinical obesity are aligned indicating that the rodent can be an useful tool to study the interplay between diet, obesity and pain. In both cases weight gain might represent only a minor contribution to abnormal pain manifestation.
PubMed: 34195483
DOI: 10.1016/j.ynpai.2021.100066 -
Techniques in Coloproctology Feb 2021In recent years, there has been growing concern about the potential association of stent placement as a bridge to surgery in malignant colon obstruction and some... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
In recent years, there has been growing concern about the potential association of stent placement as a bridge to surgery in malignant colon obstruction and some anatomopathological findings that could lead to worsening long-term cancer outcomes, such as perineural, vascular and lymphatic invasion. The aim of the present review was to assess the pathological changes found in surgical specimens after stent placement for obstructing colon cancer vs. emergency surgery, and the impact of perineural invasion on survival rates METHODS: MEDLINE, Cochrane Library, Ovid and ISRCTN Registry were searched, with no restrictions. We performed four meta-analyses to estimate the pooled effect sizes using a random effect model. The outcomes were perineural, vascular and lymphatic invasion rates, and 5-year overall survival rate in patients with obstructive colon cancer, depending on the presence or absence of perineural invasion.
RESULTS
Ten studies with a total of 1273 patients were included in the meta-analysis. We found that patients in the stent group had a significantly higher risk of perineural (OR 1.98, 95% CI 1.22-3.21; p = 0.006) and lymphatic invasion (OR 1.45, 95% CI 1.10-1.90; p = 0.008). Furthermore, patients with positive perineural invasion had almost twice the risk of dying compared to those with no perineural invasion (HR 1.92, 95% CI 1.22-3.02; p = 0.005).
CONCLUSIONS
Stent placement as a bridge to surgery in colorectal cancer patients modifies the pathological characteristics such as perineural and lymphatic invasion, and this may worsen the long-term prognosis of patients. The presence of perineural infiltration in obstructed colon cancer decreases the long-term survival of patients.
Topics: Colonic Neoplasms; Colorectal Neoplasms; Humans; Intestinal Obstruction; Stents
PubMed: 33200308
DOI: 10.1007/s10151-020-02350-2 -
World Neurosurgery Apr 2021The anatomy and spatial relationships of the dural sac comprising the Meckel cave (MC) and its ensheathed trigeminal ganglion (TG) are exceedingly intricate and complex....
BACKGROUND
The anatomy and spatial relationships of the dural sac comprising the Meckel cave (MC) and its ensheathed trigeminal ganglion (TG) are exceedingly intricate and complex. There are conflicting accounts in the literature regarding the dural configuration of the MC around the ganglion and the dual embryology of the MC and TG is still unclear.
METHODS
A combined systematic and narrative literature review was conducted to collate articles addressing MC and TG anatomy, in addition to their embryology, role in tumor spread, somatotopy, and association with trigeminal neuralgia.
RESULTS
Three key anatomic models by Paturet (1964), Lazorthes (1973), and Lang and Ferner (1983) have been put forward to show the arrangement of the MC around the TG. The TG is formed from both neural crest and placodal cells and drags the enveloping dura caudally to form the MC prolongation during development. Both a mediolateral and dorsoventral somatotopic arrangement of neurons exists in the TG, which corresponds to the 3 nerve divisions, of which V2 and V3 are prone to perineural tumor spread along their course.
CONCLUSIONS
Sound knowledge concerning the dural arrangement of the MC and the trigeminal divisions will be invaluable in optimally treating cancers in this region, and understanding TG somatotopy will immensely improve treatment of trigeminal neuralgia in terms of specificity, efficacy, and positive patient outcomes.
Topics: Cranial Fossa, Posterior; Dura Mater; Humans; Neurosurgical Procedures; Trigeminal Ganglion; Trigeminal Neuralgia
PubMed: 33516868
DOI: 10.1016/j.wneu.2021.01.081 -
Cancers Aug 2023The outcomes of orbital exenteration (OE) in patients with craniofacial lesions (CFLs) remain unclear. The present review summarizes the available literature on the... (Review)
Review
BACKGROUND
The outcomes of orbital exenteration (OE) in patients with craniofacial lesions (CFLs) remain unclear. The present review summarizes the available literature on the clinical outcomes of OE, including surgical outcomes and overall survival (OS).
METHODS
Relevant articles were retrieved from Medline, Scopus, and Cochrane according to PRISMA guidelines. A systematic review and meta-analysis were conducted on the clinical characteristics, management, and outcomes.
RESULTS
A total of 33 articles containing 957 patients who underwent OE for CFLs were included (weighted mean age: 64.3 years [95% CI: 59.9-68.7]; 58.3% were male). The most common lesion was squamous cell carcinoma (31.8%), and the most common symptom was disturbed vision/reduced visual acuity (22.5%). Of the patients, 302 (31.6%) had total OE, 248 (26.0%) had extended OE, and 87 (9.0%) had subtotal OE. Free flaps (33.3%), endosseous implants (22.8%), and split-thickness skin grafts (17.2%) were the most used reconstructive methods. Sino-orbital or sino-nasal fistula (22.6%), flap or graft failure (16.9%), and hyperostosis (13%) were the most reported complications. Regarding tumor recurrences, 38.6% were local, 32.3% were distant, and 6.7% were regional. The perineural invasion rate was 17.4%, while the lymphovascular invasion rate was 5.0%. Over a weighted mean follow-up period of 23.6 months (95% CI: 13.8-33.4), a weighted overall mortality rate of 39% (95% CI: 28-50%) was observed. The 5-year OS rate was 50% (median: 61 months [95% CI: 46-83]). The OS multivariable analysis did not show any significant findings.
CONCLUSIONS
Although OE is a disfiguring procedure with devastating outcomes, it is a viable option for carefully selected patients with advanced CFLs. A patient-tailored approach based on tumor pathology, extension, and overall patient condition is warranted.
PubMed: 37686561
DOI: 10.3390/cancers15174285 -
JAMA Dermatology Feb 2023Primary cutaneous squamous cell carcinoma is usually curable; however, a subset of patients develops poor outcomes, including local recurrence, nodal metastasis, distant... (Meta-Analysis)
Meta-Analysis
Association of Patient Risk Factors, Tumor Characteristics, and Treatment Modality With Poor Outcomes in Primary Cutaneous Squamous Cell Carcinoma: A Systematic Review and Meta-analysis.
IMPORTANCE
Primary cutaneous squamous cell carcinoma is usually curable; however, a subset of patients develops poor outcomes, including local recurrence, nodal metastasis, distant metastasis, and disease-specific death.
OBJECTIVES
To evaluate all evidence-based reports of patient risk factors and tumor characteristics associated with poor outcomes in primary cutaneous squamous cell carcinoma and to identify treatment modalities that minimize poor outcomes.
DATA SOURCES
PubMed, Embase, and SCOPUS databases were searched for studies of the topic in humans, published in the English language, from database inception through February 8, 2022.
STUDY SELECTION
Two authors independently screened the identified articles and included those that were original research with a sample size of 10 patients or more and that assessed risk factors and/or treatment modalities associated with poor outcomes among patients with primary cutaneous squamous cell carcinoma.
DATA EXTRACTION AND SYNTHESIS
Data extraction was performed by a single author, per international guidelines. The search terms, study objectives, and protocol methods were defined before study initiation. A total of 310 studies were included for full-text assessment. Owing to heterogeneity of the included studies, a random-effects model was used. Data analyses were performed from May 25 to September 15, 2022.
MAIN OUTCOMES AND MEASURES
For studies of risk factors, risk ratios and incidence proportions; and for treatment studies, incidence proportions.
RESULTS
In all, 129 studies and a total of 137 449 patients with primary cutaneous squamous cell carcinoma and 126 553 tumors were included in the meta-analysis. Several patient risk factors and tumor characteristics were associated with local recurrence, nodal metastasis, distant metastasis, disease-specific death, and all-cause death were identified. Among all factors reported by more than 1 study, the highest risks for local recurrence and disease-specific death were associated with tumor invasion beyond subcutaneous fat (risk ratio, 9.1 [95% CI, 2.8-29.2] and 10.4 [95% CI, 3.0- 36.3], respectively), and the highest risk of any metastasis was associated with perineural invasion (risk ratio, 5.0; 95% CI, 2.3-11.1). Patients who received Mohs micrographic surgery had the lowest incidence of nearly all poor outcomes; however, in some results, the 95% CIs overlapped with those of other treatment modalities.
CONCLUSIONS AND RELEVANCE
This meta-analysis identified the prognostic value of several risk factors and the effectiveness of the available treatment modalities. These findings carry important implications for the prognostication, workup, treatment, and follow-up of patients with primary cutaneous squamous cell carcinoma.
TRIAL REGISTRATION
PROSPERO Identifier: CRD42022311250.
Topics: Humans; Carcinoma, Squamous Cell; Skin Neoplasms; Prognosis; Mohs Surgery; Risk Factors
PubMed: 36576732
DOI: 10.1001/jamadermatol.2022.5508