Background: Colonoscopy related fear impairs the current gold standard screening of colorectal cancer. Compared to other minimally invasive procedures for cancer screening, colonoscopy-induced anxiety exceeds the procedure through bowel preparation. Immersive virtual reality’s (iVR) role in alleviating the complex stress–pain relationship encountered during medical procedures is directly proportional to the rising affordability of state-of-the-art Head-Mounted-Displays (HMDs). Objective: to assess the effect of iVR on patients’ colonoscopy-induced anxiety and pain. Materials and methods: A systematic search was conducted in PubMed, Cochrane Central Register of Controlled Trials, Web of Science, Embase and Scopus databases up to January 2022. Clinical trials evaluating anxiety as an outcome were included without language restriction. Results: Four clinical trials were included: three on the patients’ intraprocedural anxiety and one on patient education. Intraprocedural iVR interventions for colonoscopy-induced anxiety and pain revealed a similar effect as conventional sedation, while a statistically significant reduction was reported for non-sedated patients. iVR patient education improved the quality of bowel preparation and reduced patient anxiety before colonoscopy. Conclusions: The current research highlights the need to use high-end HMDs and appropriate interactive iVR software content for colonoscopy-induced anxiety. Methodological frameworks regarding the eligibility of participants, double-blinding and randomization of iVR studies can facilitate the development of iVR implementation for anxiety and pain management. Colonoscopy still stands as the gold standard for colorectal cancer (CRC) screening and premalignant lesions worldwide in terms of sensitivity and specificity, although it is anticipated with fear. Regarding factors that influence patients’ failure to attend a scheduled colonoscopy, the most significant barrier corresponds to the emotional and cognitive manifestations of the fear of cancer, which is common in up to 45.2% of CRC screening candidates . Risk poContinuous research efforts are targeting a wider uptake of the CRC screening  through One of the traits of negative outcome during and after minimally invasive diagnostic procedures is represented by a greater perceived pain intensity that is usually related to the coexisting level of procedure-induced anxiety . The colAR: In 1966, Ivan Sutherland imagined an “ultimate display”, but the lack of graphical processing power determined a resemblance of a primitive form of AR through the first Head Mounted Display (HMD) . SutherlVR: Through “Sensorama”, Morton Heilig created in 1962 the first interactive, immersive VR (iVR) all-in-one system, meant to capture all senses of the user, from dynamic visuals, auditory, olfactive, and even vibratory sensation . In NoveThe concepts behind virtual reality (VR) and augmented reality (AR) have been intuited since the very dawn of processing units. The technical evolution and growing accessibility of consumer VR equipment are directly proportional to medical research publication trends . Even thAlthough only experimental, emerging deep learning technology can autonomously enhance current screening algorithms improving CRC diagnosis and prognosis . The risThis study aims to assess the effect of iVR on the colonoscopy-induced anxiety of patients undergoing bowel preparation and colonoscopy, either by the distraction of the patient during the procedure or by education for bowel preparation. We hypothesise that a holistic approach may offer a better perspective for previsioning over the current feasibility and future direction of iVR in colonoscopy.A comprehensive search strategy following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)  guidelinThe literature was searched independently by two authors, up to the 1st of January 2022, using the following electronic databases: PubMed, Cochrane Central Register of Controlled Trials, Web of Science, Scopus, and Embase. Due to the limited number of papers available, there were no specific language restrictions, publication dates, or publication status. We also hand-searched relevant conference abstracts or proceedings, all the references of included articles, and the grey literature from Google Scholar.The following medical subject headings (MeSH) search terms were defined :Two groups of authors  independently screened studies and were selected for full-text review. Disagreements regarding the included studies were resolved by discussion and consensus. The third group of authors (A.S.S. and C.Ș.) acted as arbitrators when an agreement was not reached.Clinical trials evaluating iVR for colonoscopy-induced anxiety were included without language restriction. Outcomes were an assessment of the influence of the intervention on the anxiety and/or pain of the participants. Types of participants: adults (>18 years of age) undergoing colonoscopy, with no restriction regarding gender. Types of interventions: any iVR intervention (iVR regarded as stereoscopic emulated software content through an HMD) with therapeutically or educational potential to lower colonoscopy-induced anxiety (intervention group), compared with the control group with conventional procedure (sedated or non-sedated) or traditional means of education for bowel preparation. We excluded studies that did not share the aforementioned characteristics through a full-text evaluation.Four iVR clinical trials were included : three sOnly three interventional studies  investigData extracted in Veldhuijzen et al., 2020  designedÇakır and Evirgen, 2021  reportedThe pilot study design by Friedman et al., 2021 had a different approach to iVR HMD exposure. He compared the same group of participants who underwent at least one colonoscopy under conscious sedation within the same health facility to evaluate the impact of iVR on procedural anxiety and pain. The exclusion criteria only addressed aspects related to the previous procedure, such as having a prior colonoscopy non-sedated or under anaesthesia, with no regard to the participant’s history of psychiatric or neurological disorders. Among the 26 that finished colonoscopy with iVR, six patients (23.1%) asked for medication during the procedure. Still, they resisted temptation as the pain was not perceived as intense enough or after being reassured by the physician that cramping was over. The results showed that the one participant that requested medication had the lowest score of 1 (weakest motivation) to the question regarding the cause for using iVR as an alternative to sedation, compared with the other 26 participants that completed iVR colonoscopy without requesting medication averaging scores in the range of 8.5–9 out of 10. Therefore, they suggest that a strong motivation for choosing iVR might be related to the patient’s determination to avoid sedation medication .p = 0.04) in the iVR group. Higher satisfaction , a greater compliance rate , and an improvement of detection rate for polyps  and adenomas  was also reported in the iVR group. The high educational, economic and social status of included patients limit the generalisation of this study results for the general population [Chen et al., 2021, analysed the effects of either conventional education or iVR education for colonoscopy bowel preparation. This 2-year prospective RCT study population included 346 randomly assigned (1:1) to one form of education. The outcomes included compliance, preparation, satisfaction, and detection rates. The authors reported a statistically significant improvement in preprocedural anxiety . Anxietypulation .The included studies used low-end HMD, which determined questionable results on colonoscopy-induced anxiety. The current study highlights the need to reduce methodological flaws to improve iVR effectiveness in lowering anxiety and pain during colonoscopy.There is a need to evaluate the iVR impact on anxiety during colonoscopy of high-end dedicated immersive HMD compared with smartphone-powered HMDs, as high-end technology should offer a greater sense of presence and perhaps distractibility during the colonoscopy procedure. For intraprocedural distraction, we emphasise the need for state-of-the-art HMD devices with high-end specifications such as an Oculus Rift or HTC Vive-Pro to offer strong enough variables in the dissociation equation consisting of the potential of immersivity (hardware and software) multiplied by software potential of distractibility. Existing studies demonstrate the superiority of higher immersivity in lowering anxiety and pain compared with non-immersive VR in paediatric populations bone pin and suture removal . As iVR The protocol of Çakır and Evirgen, 2021, was submitted to evaluate a Non-Interventional Clinical Research Ethics Committee . FriedmaIndividuals suffering from bowel inflammatory disease can develop psychiatric symptoms such as anxiety or depression . Among tRegarding the role of the software content, we emphasise the single currently approved U.S. FDA cognitive-behavioural based software for chronic pain iVR, called EaseVRx versus a sham 2D nature video; both interventions were delivered through a Pico G2 4K resolution HMD. The study results show clear superiority in over-the-counter analgesics needed for pain control and sleep and physical function improvement in the EaseVRx group. However, patient opioid analgesics requirements were not significantly influenced in any of the two interventions . The usep-value of 0.686). One of the main reasons of the patients for not choosing VR colonoscopy as an alternative to conventional sedation was the expected procedure-induced pain (p = 0.025) [A 320 participant cross-sectional study using a survey assessed characteristics that influence the patient choice of iVR colonoscopy distraction instead of conventional sedated colonoscopy. Results revealed that anxiety was not related to willingness to accept VR colonoscopy (with a = 0.025) .Nature video content and lack of interaction through controllers may not be suitable for pain and anxiety reduction in colonoscopy interventions. It does not involve patients enough, limiting the sense of presence and being perceived more as an immersive television documentary than a true distractor. The principle of distracting patients with audio-visual stimuli during the colonoscopy was researched before iVR equipment, using DVD played auditory and video content during colonoscopy as a distraction. Still, although interventions lowered anxiety, their impact did not achieve statistical significance . HistoriImmersivity can be described as iVR HMD’s potential to offer a three-dimensional or stereoscopic perspective to the user, perceived as a “presence” in a computer-generated virtual environment. There is a direct proportionality between the level of sensory involvement and their quality, resulting in an illusion perceived as “presence” . PresencAlthough how iVR exposure lowers the pain threshold has yet to be fully explained, one of the reasons may be attributed to the derealisation and depersonalisation potential of iVR exposure, a proven model of induced dissociation . The hypUsing iVR HMD for sedation in colonoscopy is a financially more viable alternative. In France, a colonoscopy procedure is nearly three times more expensive when an anesthesiologist is involved . ComparaThe most significant advantage of using iVR as an alternative to sedation is avoiding possible life-threatening adverse events associated with conventional sedation and analgesia, as seen in One of the most frequent side effects encountered after VR exposure is a form of motion sickness known as cybersickness. Cybersickness is influenced by predisposing traits such as gender but is also directly associated with certain hardware specifications such as interpupillary distance, the field of view, and image refresh rate . Even neFrom a methodological point of view, among the three included studies, only Çakır and Evirgen, 2021, evaluated eligibility for exposure to a VR environment by excluding patients diagnosed with neurological disorders such as epilepsy or balance disorders . The excBased on the reflected somatic impact of cybersickness, the documented resemblance to the somatic symptoms characterising acute anxiety events can be associated with higher perceived anxiety levels during the procedure. Individuals in the iVR group prone to simulator sickness can negatively perceive the immersive experience as physical symptoms such as dizziness, eye strain, and motion sickness over a stressful minimally invasive colonoscopy procedure. As only one study exposes the iVR group participant preliminary to procedure day, and that exposure did not assess cybersickness levels, nor was associated with procedural stress, a critical methodological issue might impair current studies designs. Currently, no existing literature directly correlates cybersickness similarities to a physical symptom of anxiety. However, many neuroscientist iVR interventional researchers stated that some SSQ items and anxiety traits are commonly encountered . AnxietyThe evaluation of post-procedural anxiety does not consider that the person receiving the screening is most probably a colorectal cancer suspect or in a risk population such as inflammatory diseases. Perhaps the best moment for a proper evaluation of procedure-induced anxiety, diminishing the chance of measuring overlayed procedural pressure related to the result of the procedure, would be at a reasonable interval after receiving a precise diagnosis. Last but not least, among all minimally invasive medical or surgical procedures, as part of a screening program, colonoscopy candidates share vulnerable psychological traits.Regarding iVR patient education, a picture speaks more than 1000 words, but an iVR video might tell the whole story. Although a good bowel preparation was demonstrated to influence colonoscopy results by raising the chances of identifying a specific lesion and even spread intervals between re-examinations , more thPatients who found that the bowel preparation instructions were clear were much less anxious about the bowel preparation (15% with high anxiety versus 36% among those who thought the instructions were confusing) .Liu Z. et al., 2017, offered a panoramic view over the worldwide encountered forms of education in colonoscopy bowel preparation, underlining the disadvantages of printed materials that do not apply in patient education or the time consuming and variability of the information offered through counselling and training sessions. Audio-visual, smartphone, and social media-based education are restricted to developed areas .Recommendations for patient education regarding bowel preparation would be represented by portable autonomous iVR HMDs. Such as Oculus Go or Oculus Quest with pre-programmed training videos that may include knowledge testing. A viable alternative for patient bowel preparation is represented by pre-programmed autonomous standalone iVR HMD devices  backed by dedicated educational software.The current advancement of iVR in education relies on being perceived as a tool for adapting the social distancing during the SARS-CoV-2 pandemic; this exponential growth trend may continue beyond the end of the restrictions. An iVR education for bowel preparation can raise patient motivation and satisfaction and offer a more precise, less interpretable perspective regarding the procedural steps of colonoscopy. Improving satisfaction and self-reported anxiety levels can improve better screening cooperation.Colonoscopy is one of the most performed minimally invasive procedures, part of national screening programs for colon cancer . Over 14.2 million colonoscopies and 2.8 million flexible sigmoidoscopies were performed in the U.S. during 2002 , with a The pandemic aftermath weighs heavily on any health system, extending the gap between the healthcare professionals and patients with a risk for colon cancer redistributing resources away from screening programs .p = 0.05) range a day before to a median anxiety score ranging from 36.2 to 44.8 (p = 0.001) on colonoscopy procedure day anxiety [The anxiety related to the possibility of contracting SARS-CoV-2 has a cumulative effect reflected in a lower screening of the risk population . Colonos anxiety .Complementary fields of minimally invasive medical procedures and modalities such as burnt patient debridement have more than a decade since proven to benefit from experimenting with computer-simulated VR exposure . Colonosp”. Similar methodological flawed designs and results were reported in other cancer screening minimally invasive procedures such as iVR cystoscopy distraction for 23 CG vs. 22 iVR group [The level of immersivity is directly correlated with reducing pain. Still, technological development speed outruns our ability to discern state-of-the-art hardware worthy of medical interventions from outdated iVR devices. Perhaps the rate of progress is more than we can process considering the preparations regarding a clinical trial; there is a chance that the equipment used will outdate before starting the study. Therefore, outdated technology is far more dangerous, reflected in the perpetual lack of correctly differentiating computer-simulated VR environments and true state-of-the-art iVR. This could directly impact progress towards implementing an already insufficiently acknowledged disruptive technology such as iVR. The results may trigger lesser enthusiasm in researchers in replicating interventional with targeted outcomes that do not obey the immovable weight of the statistically insignificant “VR group . AccordiVR group .Jae-Hyuk Yang, 2021, studied the impact of a high-end HTC Vive headset and content specific to the following arthroscopic reconstruction procedural success instead of random natural environments lowered anxiety scores by possibly targeting a psychological reassurance mechanism. This aspect can be explained by acknowledging the distractibility potential of iVR on nociceptive stimuli in both immersive and non-immersive exposure; therefore, implying that quality immersion manages to reach a level of distractibility that impairs internal cognitive processes involved in anxiety mechanisms .Finally, physicians performing invasive or minimally invasive procedures such as colonoscopy training may benefit from iVR exposure training by lowering performance anxiety. The improvement of hand coordination , greaterAccording to the definition of iVR by Grigore Burdea, it must resemble “a high-end user-computer interface that involves real-time simulation and interactions through multiple sensorial channels” . ConsideThe unique qualitative benefits of iVR implementation in colonoscopy as a sedation alternative, interface for offering patients bowel preparation education, and perhaps facilitating translation of physician simulator training to clinical practice can be cumulative if simultaneously applied in all three aspects. Therefore, raising the bar for full integration of high-end iVR in colonoscopy can progressively benefit the impact of individual interventions by accommodating both medical staff and patients to use and provide feedback regarding the promotion of this disruptive technology towards its potential.Limitations: As an emerging medical technology, there are few published iVR interventional studies in colonoscopy that significantly differ methodologically even when targeting the same populations, interventions, outcomes and using similar hardware tools. The current small sample sizes emphasise the need for more research to ensure the validity of the iVR approach targeting colonoscopy-induced anxiety and pain. In the absence of a commonly approved framework, the pursuit of outcomes is based on what directions the investigators consider worthy. This aspect leads to heterogenous gathered results, less poolable for relevant statistical analysis. The iVR techniques’ potential has been recently evaluated for colonoscopy anxiety; the novelty of the research topic is associated with only a handful of currently published papers.Current clinical trials regarding intraprocedural use of iVR for colonoscopy-induced anxiety and pain share the common methodological flaw of using low-end iVR and non-interactive software. Intraprocedural iVR interventions for colonoscopy-induced anxiety and pain reveal superiority to non-sedated colonoscopy and share similar effects compared to sedated colonoscopy. Future studies should have common frameworks to gather homogenous data for statistical analysis. Directions of study designs regarding the impact of iVR on anxiety should optimise the eligibility of participants, double-blinding process, randomization and SSQ implementation.An iVR patient education for bowel preparation represents a promising educational tool that lowers the preprocedural anxiety of the patient.iVR HMD interventions have the potential to become an alternative for anxiety and pain management in colonoscopy, especially when sedation is undesired or specifically contraindicated. However, more research is needed regarding this field.


Aging is associated with an increased risk of COVID-19 morbidity and mortality. In this study, we tested whether the pandemic influenced how old individuals felt by examining longitudinal within-person changes in subjective age. We tested two alternative hypotheses: (a) people felt increasingly older in response to the stress generated by COVID-19; (b) people felt increasingly younger due to psychological distancing from older age. We tested these hypotheses in a large US sample of adults assessed once before and twice during the COVID-19 pandemic. Multilevel analyses indicated that people reported feeling younger with the emergence of COVID-19. We further tested demographic, health, and psychosocial predictors of changes in subjective age. Overall, the findings supported the hypothesis that subjective age partly reflects a coping process of psychological distancing from older age, a process that parallels physical and social distancing.


Epidural fibrosis is a common cause of pain after lumbar surgeries. There are no previous reports documenting profound limb weakness associated with epidural fibrosis. A 43-year-old woman uneventfully underwent microscopic discectomy. However, six additional surgeries were needed due to recurrent pain and weakness episodes, several days after the surgery. Operative findings were severe epidural fibrosis around the thecal sac and nerve roots. Epidural fibrosis excision did not prevent recurrent fibrosis; therefore, we performed a lordotic fusion with posterior column shortening to reduce neural tension and nerve-root stretching. Eventually, she became free from recurrent episodes of deteriorations and repetitive surgeries. Lumbar discectomies are surgical procedures that are commonly performed in patients with herniated lumbar intervertebral discs. Previous studies have reported that 20–40% of patients have persistent or recurrent sciatica or intractable back pain ,6,7,8,9.A 43-year-old woman presented to our hospital with a radiating pain in her left lower extremity. The visual analogue scale (VAS) score in her legs was 9. Magnetic resonance imaging (MRI) showed an L5/S1-level left central herniated disc. Computed tomography (CT) revealed combined posterior ring apophysis fracture at the same level . ConservEleven days after surgery, she was admitted to the emergency room due to severe pain in her back and left lower extremity. There was no clinical evidence of systemic infection  or wound problem . MRI revealed no evidence of recurred or remnant disc. However, diffuse enhancement at the posterior epidural space from L4 to S1 levels and around the peridural space at the L5/S1 level  was noteCandida albicans was identified, and treated successfully with antifungal agents. Follow-up MRI at 6 months postoperatively showed a well-decompressed thecal sac and nerve roots. However, roots were clumped and distorted within the thecal sac, suggesting arachnoiditis . Revision surgery revealed severe epidural fibrosis along the thecal sac and L5–S1 roots (left side dominant). Normal dura was identified after peeling the thick epidural fibrosis . Pain annoiditis . FortunaWe have presented a case of multiple revision surgeries following discectomy, resulting from recurrent episodes of postoperative pain and weakness in the left lower extremity. Although surgical treatment should be considered as the last resort in a case of FBSS ,16,17, rDuring the repetitive surgeries, the only intraoperative abnormal findings were exaggerated tense dura mater with thick fibrosis and fixed nerve roots. Therefore, postoperative epidural fibrosis was thought to have caused the recurrent episodes of pain and neurological deficit. Previous studies have reported that efforts of repeat decompression and neurolysis are discouraging ,16,17; tEpidural fibrosis is known to be a common cause of pain following lumbar spinal surgery, and has been implicated in 8% to over 60% of cases of post-laminectomy syndrome ,12,13,14In epidural fibrosis, fibrous scar tissue replaces the epidural fat and can cause compression of the dura mater and nerve roots, leading to their adherence and tethering to the surrounding structures . In suchBlood supply to the nerve roots could be compromised by fibrotic change and dura mater compression. In contrast to the blood supply of the peripheral nerves, which is mostly transported by intrinsic vasculature, more than half of the nerve roots are transported from the extrinsic system via diffusion through the cerebrospinal fluid . In the Recurrent episodes of profound weakness in left lower extremity, in the setting of epidural fibrosis, are quite strange. We could not find any previous reports with epidural-fibrosis-associated limb weakness. However, one report exists demonstrating a decreased blood flow to the nerve roots being associated with electrophysiological deterioration during the SLR test. Takamori et al. reported that the amplitude of compound muscle action potential (CMAP) deteriorated significantly after the nerve stretching test. Significant correlations were found between the deterioration ratio of nerve-root blood flow and CMAP . The decThe possible mechanisms of repetitive episodes of the patient’s clinical deterioration were supposed to be a combination of mechanical stress and impaired blood supply resulting from epidural fibrosis, especially with markedly increased susceptibility stresses due to unknown reasons. Repetitive excision of epidural fibrosis could not cease the vicious cycle; therefore, we performed lordotic fusion to reduce neural tension and stretching of the nerve roots. Eventually, the patient became free from recurrent episodes of clinical deteriorations and repetitive surgeries. Therefore, in a case of suspicious epidural fibrosis combined with recurrent episodes of clinical deteriorations, lordotic fusion with posterior column shortening may be a treatment option.In the present study, we reported a patient suffering from recurrent episodes of clinical deterioration with massive epidural fibrosis following lumbar surgeries. The possible mechanisms were a combination of mechanical stress and impaired blood supply resulting from epidural fibrosis, with markedly increased susceptibility for stressed patients. In a case of suspicious epidural fibrosis combined with recurrent episodes of clinical deteriorations, lordotic fusion with posterior column shortening may be a treatment option.


Commissural alignment during transcatheter aortic valve implantation (TAVI) has important clinical implications as TAVI expands to younger patients in whom lifetime treatment of aortic valve disease and coronary artery disease is of particular importance. Numerous studies have shown that lack of commissural alignment may adversely affect coronary reaccess and the feasibility of redo-TAVI in this patient population. To assess the risk of commissural misalignment more accurately, we have pioneered and validated the use of a preprocedural imaging protocol that determines valve orientation using multi-detector computed tomography-fluoroscopy co-registration. Furthermore, we have shown that a modified delivery system insertion technique during initial valve deployment results in improved commissural alignment and reduced coronary artery overlap following TAVI with a self-expanding device. However, numerous unanswered questions remain about the impact of commissural misalignment on balloon-expandable valve-in-valve TAVI, especially in patients with unfavorable aortic root anatomy. It is imperative that clinicians consider these anatomic, device-related, and procedure factors, among others, when evaluating patients for transcatheter therapies. Amidst these rapidly evolving clinical indications, several issues related to the long-term durability and feasibility of TAVI in younger patients have been raised by the structural heart community. One such example is transcatheter heart valve (THV) orientation during initial deployment and its impact on commissural alignment. Whereas direct visual inspection and excision of native leaflets during surgical aortic valve replacement (SAVR) readily allows alignment of the surgical valve commissures with the native commissures, commissural alignment with THVs during TAVI is far more inconsistent and random. Commissural malalignment may lead to varying degrees of overlap between the neo-commissural posts and coronary arteries,5. Furthermore, experimental models have shown that THV leaflet stress and central aortic regurgitation (AR) may be exacerbated with suboptimal commissural alignment,6. These findings have significant clinical implications for younger patients who have an increased lifetime risk of complications of aortic valve disease and coronary artery disease. Given that coronary reaccess and redo-TAVI will become more prevalent in the future, achieving commissural alignment during initial TAVI may impact the feasibility of both these procedures. Here, we review some of the salient features of neo-commissural alignment and offer our perspectives on how to achieve a more physiologic valve implantation.With the conclusion of the recent low-risk trials, transcatheter aortic valve implantation (TAVI) has now been approved for patients with symptomatic, severe aortic stenosis across all surgical risk categories. Coronary reaccess is impeded not just by the obstructive THV stent frame, but also by an in situ barrier formed by the native aortic leaflets. Thus, the anatomy relating the aortic root to the valve stent frame must be thoroughly evaluated. The coronary arteries are easily reached when the sinotubular junction (STJ) or coronary ostia are situated distal to the transcatheter valve stent frame. However, when either of these structures is located below the THV frame, the TAVI operator would need to cross the stent frame to access the coronary arteries. This may not be a major issue when using THVs with short stent frame heights provided that the native aortic valve does not obstruct the open cells of the stent frame.Contemporary THV device and delivery system designs do not allow for consistent and precise commissural alignment. Following initial TAVI, an obstructive commissural post may significantly hinder future coronary access by extending above, in front of, or through the coronary ostia. Thus, consideration of the THV leaflet height within the anatomic boundaries of a patient’s aortic root becomes crucial when evaluating him or her for redo-TAVI. As before, if the leaflets lie proximal to the coronary ostia, valve-in-valve TAVI should be feasible. If not, an adequate margin between the valve stent frame and sinotubular junction is imperative to prevent sinus sequestration and coronary obstruction.Commissural misalignment during initial TAVI also jeopardizes the success of future valve-in-procedures for the treatment of prosthetic valve failure. While TAVI-in-SAVR is a relatively simple procedure, redo-TAVI in the current era is associated with a number of anatomic risks, including coronary obstruction, that are exacerbated in the absence of neo-commissural alignment. However, this procedure may not be as easily performed during redo-TAVI, especially with supra-annular THVs since leaflet splitting can be impeded by the valve stent frame. In cases of commissural misalignment that appose the commissural post to a coronary ostium, the BASILICA technique may not completely eliminate the possibility of coronary obstruction in redo-TAVI.In recent years, the BASILICA  procedure has been successfully applied in TAVI-in-SAVR cases with a high risk of coronary obstruction. Briefly, we begin by measuring the en-face angle between the left main and right coronary arteries using MDCT. Next, using the 3Mensio Valves software , we capture the THV orientation in the three-cusp coplanar fluoroscopic view and co-register it onto our coplanar MDCT axial images. We can then superimpose a virtual image of either the SAPIEN 3 THV  or the Evolut THV  over the axial MDCT annular and sinus of Valsalva images derived from the 3Mensio Valves software. This allows us to determine the degree of overlap between the neo-commissures and the coronary ostia. Note that the use of various third-party software systems introduces the risk of operator bias that has to be taken into consideration when performing the aforementioned analyses.Accurate imaging is essential for preprocedural planning. To assess the risk of commissural misalignment and severe coronary overlap, our group pioneered the technique of determining THV orientation using multi-detector computed tomography (MDCT)-fluoroscopy co-registration. The nuances between the two main types of commercially available THVs in the context of the ALIGN-TAVR and other contemporary studies are discussed below.We have previously used the aforementioned co-registration technique to assess the relationship between THV deployment orientation and commissural alignment as part of the ALIGN-TAVR  study. Here, > 30%-50% of the 828 patients who underwent TAVI from 2016–2019  had overlap with at least one coronary artery. More importantly, commissural alignment was unaffected by initial deployment orientation of the SAPIEN 3 THV, but was significantly improved by specific initial orientations of the Evolut and ACURATE THVs. We speculated that this may be due to the flexibility of the delivery catheter as it courses through the aorta. Fortunately, the unassuming profile of SAPIEN 3 stent frame renders commissural alignment less pertinent for coronary reaccess as wires and catheters can engage the coronary ostia above and through the top row of the stent frame. Coronary access can nevertheless be challenging in certain cases where the SAPIEN 3 stent frame protrudes beyond a narrow STJ,14.The balloon-expandable SAPIEN 3 valve can have one commissure crimped at the 3, 6, 9, or 12 o’clock orientation relative to the delivery catheter to track the initial deployment orientation. In the ALIGN-TAVR study, commissural alignment was not improved by crimping the SAPIEN 3 THV at each of the aforementioned orientationset al. in their study of 137 low surgical risk patients from the LRT (Low Risk TAVR) trial (NCT02628899) who underwent balloon-expandable TAVI. Using post-TAVI MDCT analysis, the authors found that 9%-13% of patients displayed high-risk alignment due to the valve stent frame extending distal to the coronary ostia and an obstructive commissural post. Similar to the ALIGN-TAVR study, commissural alignment was not significantly influenced by intentional crimping of the transcatheter valve. The THV stent frame protruded beyond the STJ in 21% of patients, and the THV-STJ margin was < 2 mm in 13% of patients. Patients with THV-STJ margin < 2 mm were deemed anatomically unsuitable for redo-TAVI given the excessive perceived risk of coronary obstruction. Despite limited generalizability, the findings from this anatomic simulation corroborate the results from our pilot angiographic study that show that redo-TAVI may not be possible in > 20% of SAPIEN 3 patients and more than half of those with unfavorable aortic root anatomy (sinus height < THV height).Similar findings were reported by Rogers P = 0.002) and reduced coronary artery overlap by 36%-60% (P < 0.05). Perhaps most importantly, we found that the best method to achieve OC/CF “Hat” orientation involves starting with the flush port at 3 o’clock during insertion of the delivery catheter into the femoral artery.Commissural alignment is particularly important for facilitating coronary reaccess following Evolut TAVI since this supra-annular valve extends above the STJ and coronary ostia. The Evolut THV has a unique “Hat”marker that can be oriented during initial deployment in one of four positions: anterior or posterior in the center of the deployment device [center front (CF) or center back (CB)] or in the inner (IC) or outer curve (OC) of the aortic annulus . In the NCT02701283) CT sub-study who underwent transfemoral TAVI using the conventional delivery system insertion technique (flush port at 12 o’clock) were compared to 240 patients from our institution who underwent deployment using a modified technique (flush port at 3 o’clock). Unsurprisingly, the modified technique significantly improved “Hat” marker orientation at OC/CF during initial deployment , improved commissural alignment, and reduced severe coronary overlap . Note that we insert the delivery catheter at 3 o’clock but let the system self-rotate as it goes inside the body. We do not force the system to maintain the 3 o’clock position as it tracks to the annulus, just like we never force the catheter to maintain the 12 o’clock position when using the conventional technique. We do not recommend force-rotating the delivery catheter inside the patient given the risk of damaging the catheter.The above findings were validated in a recent analysis of the impact of delivery system insertion technique on commissural alignment. Here, 154 of 249 patients from the Evolut Low Risk trial  or in the inner/outer curve of the aortic annulus . Note that the “C-tab” is loaded 90Fluoroscopic images depicting deployment of a 26 mm Evolut Pro valve are shown here. Note that the “Hat” marker is positioned anteriorly in the center of the deployment device (“center front”), with the C-tab seen at the inner curve of the ascending aorta. Multi-detector computed tomography analyses indicate good commissural alignment.


Glioblastomas carry a poor prognosis and usually presents with heterogeneous regions in the brain tumor. Multi-parametric MR images can show morphological characteristics. Radiomics features refer to the extraction of a large number of quantitative measurements that describe the geometry, intensity, and texture which were extracted from contrast-enhanced T1-weighted images from anatomical MRI and metabolic features from PET. It also provides a qualitative image interpretation as well as cellular, molecular, and tumor properties. Thus, it derives additional information about the entire tumor volume which is generally of irregular shape and size from routinely evaluated “non-invasive” imaging biomarkers techniques. We demonstrated volumetric habitats and signatures in necrosis, solid tumor, peritumoral tissue, and edema with key biological processes and phenotype features. This provides physicians with key information on how the disease is progressing in the brain and can also give an indication of how well treatment is working.Glioblastoma (GBM) is a fast-growing and aggressive brain tumor of the central nervous system. It encroaches on brain tissue with heterogeneous regions of a necrotic core, solid part, peritumoral tissue, and edema. This study provided qualitative image interpretation in GBM subregions and radiomics features in quantitative usage of image analysis, as well as ratios of these tumor components. The aim of this study was to assess the potential of multi-parametric MR fingerprinting with volumetric tumor phenotype and radiomic features to underlie biological process and prognostic status of patients with cerebral gliomas. Based on efficiently classified and retrieved cerebral multi-parametric MRI, all data were analyzed to derive volume-based data of the entire tumor from local cohorts and The Cancer Imaging Archive (TCIA) cohorts with GBM. Edema was mainly enriched for homeostasis whereas necrosis was associated with texture features. The proportional volume size of the edema was about 1.5 times larger than the size of the solid part tumor. The volume size of the solid part was approximately 0.7 times in the necrosis area. Therefore, the multi-parametric MRI-based radiomics model reveals efficiently classified tumor subregions of GBM and suggests that prognostic radiomic features from routine MRI examination may also be significantly associated with key biological processes as a practical imaging biomarker. Glioblastoma multiforme (GBM) is the most lethal and aggressive primary brain tumor in adults; with a poor prognosis despite surgical resection combined with radiotherapy and temozolomide administration, the two years survival rate remains at 27% . The 201Recently, radiomics has been increasingly exploited to extract and analyze quantitative imaging features. The novel technique becomes more popular in data mining, especially in radiomics features. It can approach tumor phenotypes using thousands of image features that result in the basis for cluster shape, pixel intensity histogram, texture, and diffusion kurtosis analysis covering the entire tumor volume . SeveralThis study implemented semiautomatic annotation from T1-CE MR images for individual measurement in specific necrosis, solid part tumor, peritumoral tissue, and edema regions to extract 1316 features on the raw MR images. We represented radiomic features based on imaging signatures of the heterogeneous GBM tumor tissue parts  and creaIn addition, we presented multi-parametric MRI-based radiomics analysis to identify entirely volumetric habitats as well as ratios of these tumor components, focused on local GBM cohort and the publicly available GBM dataset from The Cancer Imaging Archive (TCIA). To investigate which biological processes derive volumetric tumor phenotype features in this study, we performed a quantitative analysis in two cohorts based on semantic feature in ground truth images using a data analysis. The ratios of volumetric features were significantly associated with various sets. Thus, the feature-based quantitative value in subregions has shown its potential biomarker as an additional source of diagnostic and therapeutic information, and information from routinely acquired MRI exams can also be notably associated with key biological processes that affect the response to chemotherapy in GBM.This study recruited a cohort of 54 patients diagnosed with primary (de novo) confirmed GBM. Two datasets were collected, with 23 patients with GBM from local hospitals as the training data cohort and 31 TCIA datasets as our validation cohort after receiving the institutional review board of Hualien Tzu Chi Hospital approval (IRB110-007-B). All local patients suspected of having cerebral GBM based on conventional radiologic findings were enlisted in this prospective study before any treatment , and imaging was performed between October 2014 and February 2019. The inclusion criteria were as follows: (1) neuropathological evaluation following surgery or stereotactic biopsy, with all lesions being histopathologically confirmed grade IV glioma; (2) available preoperative MRI consisting of gadolinium-based contrast-enhanced T1-weighted images (T1-CE), T2-weighted images (T2-WI), T2-weighted fluid-attenuated inversion recovery (T2-FLAIR) images, and apparent diffusion coefficient (ADC) images. We retrieved 31 patients with GBM from the publicly available TCIA database as the validation cohort . This dataset was released by the BraTS challenge, in which the MRIs were also used to segment GBM patients fluoroethyl)-L-tyrosine, 18F-FET) is a promising tracer that has manifested convincing results, especially in the diagnostics of brain tumors [Several literatures have proposed to evaluate the feature-based different modality in patients with GBM. The feature findings were compared with MRI and PET/MRI based on radiomics analysis  4,9,10,,19,20,21n tumors ,24,25,26Semiautomatic segmentation represents the classification for response assessment using volumetric measurements that may capture tumor shape and geometry more accurately; this is particularly useful for GBMs, which are often irregularly shaped. In addition, large-scale studies have proven the benefits of using volumetric-based radiomics features for tumor segmentation compared with intricate verification approaches ,8. To enFirst, different GBM regions were accurately labeled into four ROIs and joint intensity color-maps on T2-FLAIR in heterogeneous tumor regions ; on the Second, our investigation provided qualitative image interpretation in GBM subregions and radiomics features in quantitative usage of image analysis, as well as volumetric feature ratios  of these tumor components. The proportional volume size of the edema was about 1.5 times larger than the size of the solid part tumor, which means the edema was mainly enriched for homeostasis. Whereas the solid part was approximately 0.7 times in the necrosis area. Consequently, the multi-parametric MRI-based radiomics model revealed quantitative and qualitative information in four subregions of GBM. The novelty of this study was that we could mine images to discover patterns that predict biological characteristics of the radiomics features from these points of views.Third, computational features were extracted using annotated imaging, particularly those that quantify shape and margin sharpness. Both color-coded semantics and features were derived from multimodal MR radiomics to analyze GBM texture features and compare tumor characteristics such as entropy and homogeneity and correlate them with spatial-habitat imaging. All features were combined and fed into the machine learning algorithms for accessing and interoperating with the semantic content in medical imaging. The AUC is the best classification in all subregions on which to stratify the training data to improve machine-learning-based brain tumor region classification in comparison to other studies.(1)Edema was mainly enriched for homeostasis. The proportional volume size of the edema was about 1.5 times larger than the size of the solid part tumor. The volume size of the solid part was approximately 0.7 times in the necrosis area. Therefore, the multi-parametric MRI-based radiomics model efficiently classified tumor subregions of GBM, and there are implications that prognostic radiomic features from routine MRI examination may also be significantly associated with key biological processes that affect response to chemotherapy in GBM as a practical imaging biomarker.(2)The volumetric prototype plot is underlain by original tumor habitat that contains the tumor subregions. Generally, many more biological processes were significantly associated with the feature ratios, usually showing a trend towards a mix of pathways associated with the individual features . In our (3)Contrast enhancement was enriched for signal transduction and protein-folding processes. The peritumoral tissue is a small region in GBM in comparison with other subregions. However, these features were enriched for biological processes in immune response and apoptosis from spatial immunoprofiling while the abundance and phenotype of tumor infiltration lymphocytes are closely linked with clinical survival ,27. That(4)Biological features correlate with corresponding MR imaging sequences because different MR imaging sequences come with diverse clinical imaging protocols. Quantitative features provide tumor microenvironment, spatial characteristics, distinguishing of molecular subtypes, survival predictor corresponding to LBP and histogram of oriented gradients, scale-invariant feature transform, histogram of contrast-enhanced tumor MRI, and contrast information between co-occurring subregions, respectively. Consequently, selection of MR imaging sequences can directly affect image feature definition and the corresponding biological interpretation . Particu(5)We illustrated radiomic features based on imaging signatures of the heterogeneous GBM tumor tissue parts  and creaTo investigate which biological processes derive volumetric tumor phenotype features in this study, we performed a quantitative analysis in two cohorts based on semantic features in ground truth images using a data analysis. We compared these results to radiomics features; in our analysis, the ratios of volumetric features were significantly associated with various sets. The results of this study outline issues of major concern: Several aspects have crucial challenges for accurate features. This plays a pivotal role when it comes to extraction of radiomics-based imaging signature and the large number of quantitative measurements in two cohorts. The first challenge is variability in tumoral extraction: tumor heterogeneity causes and consequences. In 2010, Marusyk et al.  proposedThe second challenge is generalizability: The multi-parametric radiomics-based approach provides extraordinary potential and possibility to contribute to an improved diagnosis and treatment guideline in neuro-oncology. However, a few barriers must be overcome before this method can be successfully integrated into clinical routine. The reproducibility and transferability of the developed models and the underlying radiomics features should also be improved . These pThe third challenge is the small sample size of limitation. Our study focused on semantic and volumetric phenotype features such as the radiomics-based definitions of imaging phenotypes that are available. However, we attempted to compare our results with real-world clinical experience and across different types of study for correlation with radiomics feature accuracy and efficiency related to specific regions of GBM. We expect that in future studies the prognostic performances will increase cohorts with even larger numbers of samples and generalizability image processing will become available for GBM.The development of bioinformatics technology has expedited the identification of neoantigens as shown in The present study leveraged radiomic features based on imaging habitats and signatures of the heterogeneous GBM tumor tissue parts and created a volumetric radiomic-based model for the semiautomatic annotation of GBM using MRI, ground truth, and machine learning. Volumetric features were significantly associated with various sets of tumor phenotype features and biological processes. In this perspective, non-invasive biomarkers can reflect underlying tumors’ habitats and signatures to provide quantitative information to lead therapy for guiding personalized disease diagnosis, treatment evaluation, and prognostic prediction in precision medicine.


Trans-scaphoid lunate dislocation with volar displacement into the wrist/distal forearm is a devastating injury that most commonly occurs under situations of forceful impact to an extended wrist. Due to ligamentous disruption as well as fragile blood supply, these Mayfield type 4 injuries are associated with significant morbidity and long-term sequelae. Current treatment approaches to lunate dislocations depend on the severity and chronicity of the injury in addition to patient factors, with operative management potentially including ORIF or proximal row carpectomy. We report 5 cases of this rare injury pattern in 4 different patients. Trans-scaphoid lunate dislocation is a very rare carpal injury that most commonly occurs in cases of high energy trauma to an outstretched hyperextended wrist. In such cases, there is typically volar dislocation/displacement of the lunate and scaphoid into the volar soft tissues of the wrist and forearm, with the severity of trauma often dictating how far these 2 carpal bones travel up the forearm. The relatively more common perilunate dislocation indicates disruption of the capitolunate articulation with dorsal dislocation of the capitate, whereas the relatively rare lunate dislocation indicates separation of the lunate from both the radius and the carpal bones with volar dislocation of the lunate through the space of Poirier. This injury pattern has been classically described using a 4-stage classification system originally formulated by Mayfield et al. . Stage 1We report a case series of 5 instances of trans-scaphoid lunate dislocation in 4 different patients. This is the largest case series of this entity to date with radiographic documentation.A 41-year-old male presented after a motorcycle crash. The patient reported paresthesias in a right median nerve distribution. He was subsequently found to have a left pneumothorax requiring chest tube placement, left rib fractures, facial fractures, bilateral ankle fractures, left proximal ulnar fracture, and a right wrist deformity. Right wrist radiographs showed a trans-scaphoid lunate dislocation with severe volar displacement of the scaphoid fracture fragment and the lunate a.Fig 1aPOn the fifth day post injury, the patient underwent right wrist surgery including proximal row carpectomy, carpal tunnel release, and excisional debridement of the forearm b. Note tA 33-year-old male presented with multiple traumatic and burn injuries after jumping out from the third story window of a burning building. He had bilateral wrist deformities.On the right, the patient had an elbow dislocation, distal radial diaphyseal fracture and distal radioulnar joint dislocation , and trans-capitate trans-scaphoid lunate dislocation a. On theThe patient was admitted to the orthopedic service and received corrective surgeries on the second and third days of admission. The patient underwent ORIF of the right open radius fracture, right radial head arthroplasty, repair of right elbow collateral ligaments and capsule, and right volar forearm fasciotomy. He also underwent bilateral proximal row carpectomies, bilateral capitate screw fixation, bilateral dorsal spanning plate and screw fixation across the wrist, bilateral DRUJ pinning, bilateral TFCC repair, and debridement of the bilateral open wrist fractures c.Fig 2cPThe surgeries were successful and without any complications. The patient was discharged to a rehabilitation facility. On follow-up visits, he complained of residual pain, paresthesias, and limited range of motion in the right wrist. He subsequently suffered additional fractures of the right ulna and radius requiring further surgery. The worse outcome on the right was likely related to the more extensive and severe injuries he initially suffered on that side.A 19-year-old male presented after a high-speed motor vehicle crash that resulted in ejection. On arrival, he was intubated and became hemodynamically unstable, hypotensive and tachycardic in the radiology suite. He was found to have a right hemopneumothorax and an emergent thoracostomy with chest tube insertion was performed.Initial physical exam and imaging revealed several skeletal injuries. In the left upper extremity, his injuries included a trans-ulnar styloid trans-triquetral trans-scaphoid lunate dislocation and third and fourth metacarpal base fractures a.Fig 3aPOn day 3 of admission, the patient underwent pinning of the left carpal bones and the third and fourth metacarpal fractures, and screw fixation of the ulnar styloid fracture b. A leftOn follow-up visits, the patient reported significant left wrist weakness and loss of grip strength but minimal pain. Radiographs showed progressive collapse and resorption of the scaphoid and lunate, likely sequelae of AVN c. Wrist A 28-year-old male presented as a transfer from an outside hospital following a motorcycle crash. He reported pain in the right wrist.Right wrist radiographs revealed a trans-radial styloid trans-scaphoid lunate dislocation a. ClosedTrans-scaphoid lunate dislocation is a very rare injury occurring mainly in high energy trauma where force is directed upon a hyperextended wrist. The most common mechanisms cited are falls, automobile accidents, and motorcycle crashes, all of which were seen in this case series. In Patient 1, the lunate not only dislocated volarly but also made its way into the distal portion of the forearm through the carpal tunnel. Volar dislocation of the lunate may cause nerve impingement and median nerve paresthesias. Stanbury et al. reported acute median nerve symptoms in about 24 to 45% of these patients, mentioning that swelling or contusion from trauma may play a role in symptoms . They alIn terms of approaching these injuries, achieving the diagnosis in a prompt manner has been shown to be of utmost importance, and therefore radiologists play a critical role . In a muFormal consents are not required for the use of entirely anonymized images from which the individual cannot be identified - for example, x-rays, ultrasound images, pathology slides or laparoscopic images, provided that these do not contain any identifying marks and are not accompanied by text that might identify the individual concerned.


Cutaneous metastases occur in approximately 10% of oncology patients as a feature of a persistent solid tumor or the harbinger of recurrent neoplastic disease. However, they can be the presenting manifestation of an unsuspected visceral malignancy in one percent of previously cancer-free individuals. Metastatic skin lesions from breast carcinoma are diverse in their appearance. The clinical presentation of cutaneous metastases in three women with breast cancer is described and both the morphology of skin metastases caused by breast carcinoma and the conditions that are mimicked by breast cancer cutaneous metastases are reviewed. Skin metastases from breast carcinoma commonly appear as firm, flesh-colored to red, smooth or ulcerated or crusted, nodules, papules, and plaques on the ipsilateral chest wall and breast. However, unique sites of breast cancer cutaneous metastases are the eyelids, inframammary folds, ipsilateral lymphedematous arm, scalp, subungual nail bed, and umbilicus; in addition, skin metastases can occur in mastectomy scars and radiation therapy ports. Carcinoma erysipelatoides, carcinoma telangiectoides, and carcinoma en cuirasse are classic patterns of skin metastases that can be observed in breast cancer patients; carcinoma hemorrhagiectoides is a recently observed skin metastases pattern that has also been noted in oncology patients with breast carcinoma. The pleomorphic skin lesions of breast cancer metastases can masquerade as benign cutaneous lesions and tumors , cutaneous malignancies (such as melanoma and non-melanoma skin cancers), infections , reactive erythema , skin conditions , and vascular lesions . In addition, breast carcinoma cutaneous metastases can not only mimic other miscellaneous conditions such as erosions and ulcers, Paget’s disease, and papillomatosis cutis lymphostatica but also have unusual morphology such as targetoid lesions or a sharply demarcated red infiltration of the nasal tip similar to a clown’s nose. The possibility of a breast cancer cutaneous metastasis should be considered in the evaluation of a patient with breast cancer--and although less likely, in a cancer-free individual--who develops a new and/or a treatment-unresponsive cutaneous lesion. A biopsy of the skin lesion is necessary to confirm the diagnosis of breast cancer cutaneous metastasis. Cutaneous metastases from visceral malignancy are uncommon. They can be the clinical presentation of progressive neoplasm or the harbinger of recurrent disease in an oncology patient. Rarely they are the presenting manifestation of a previously undiagnosed cancer -3.Breast cancer is the most frequent malignancy in women. It is also a common neoplasm associated with cutaneous metastases. The morphology of the skin lesions secondary to metastatic breast cancer is variable in appearance -20.Cutaneous metastases that developed in three women with breast cancer are described. They appeared as annular erythema, carcinoma en cuirasse, carcinoma erysipelatoides, an erythematous targetoid lesion, and/or zosteriform metastases. The pleomorphic appearance of breast cancer cutaneous metastases is reviewed.Case 1A 47-year-old Hispanic woman presented for evaluation of possible cellulitis involving her left breast. She had been diagnosed with invasive ductal breast cancer of her left breast 10 months earlier. Her tumor was positive for estrogen receptor and negative for both progesterone receptor and human epidermal growth factor receptor 2 (HER2).Since her diagnosis, she was initially treated with weekly paclitaxel for 12 weeks. She then received every three weeks four cycles of 5-fluorouracil, epirubicin, and cyclophosphamide (FEC). She was scheduled for a mastectomy in six weeks; however, a month after the final treatment she developed an asymptomatic red rash on her left breast.Cutaneous examination showed a painless erythematous patch on the superior aspect of her left breast above the areola Figures , 2. The A biopsy, using the punch technique, demonstrated metastatic cancer cells--consistent with breast origin--in the dermal lymphatics. Correlation of the clinical presentation and pathologic findings established the diagnosis of carcinoma erysipelatoides. The mastectomy was postponed, and her progressive breast carcinoma with new cutaneous breast cancer metastases was treated with additional chemotherapy.Case 2A 54-year-old Greek woman presented with extensive and progressively enlarging skin lesions on her chest and abdomen. Two years earlier, she had been diagnosed with triple-negative invasive ductal carcinoma of the left breast. Her tumor did not express estrogen receptor, progesterone receptor, or HER2.She presented with her initial cutaneous breast cancer metastasis a year after diagnosis. This appeared as a nodule on her left chest wall. During the subsequent 12 months, she continued to develop new skin metastases.Her metastatic skin lesions had several morphologies Figures , 4. Her Punch biopsies of the affected areas demonstrated metastatic tumor cells (consistent with breast carcinoma) not only between the collagen bundles in the dermis but also filling the dermal lymphatics. Correlation of the clinical presentation and pathologic findings established the diagnoses of carcinoma en cuirasse, carcinoma erysipelatoides, and zosteriform cutaneous metastases.Case 3A 54-year-old Caucasian woman presented for evaluation of new skin lesions on her right breast and left chest. She had been in an automobile accident, in which the airbags from the car had contacted the affected areas, four months earlier. The itchy red rash had appeared three months later, and she thought the new lesions were dermatitis resulting from contact with the airbags during the car accident.She had been diagnosed with invasive ductal breast cancer of her left breast two and a half years earlier. Management (during the year following diagnosis) had included chemotherapy, mastectomy of the left breast, and radiation therapy to the left chest wall. Thereafter, she received trastuzumab for four months and was currently being treated with daily anastrozole for the last 15 months.Cutaneous examination showed several erythematous patches on the right breast and the left chest Figures , 6. MostBiopsy of the erythematous patches on the right breast and the left chest both showed metastatic carcinoma (compatible with the patient’s primary breast cancer) in the dermis and within the vascular spaces. Correlation of the clinical presentation and pathologic findings established the diagnosis of cutaneous breast cancer metastases--both within and outside of the radiation therapy port--appearing as targetoid and annular erythema, which the patient initially interpreted to be dermatitis.A retrospective study observed the incidence of cutaneous metastases to be 10% (420 of 4020) of oncology patients. In 7.6% (306 of 4020) of these individuals, the initial feature of extranodal metastatic cancer was skin metastasis. Indeed, in one percent (70 of 7316) of cancer patients, the cutaneous metastasis was the presenting manifestation of unsuspected cancer [The morphology of metastatic skin lesions from breast carcinoma is diverse Table  1-20]. -20. 1-20Three classic patterns of cutaneous metastases, frequently associated with breast cancer, have been described. They include carcinoma erysipelatoides, carcinoma telangiectoides, and carcinoma en cuirasse. The fourth pattern of metastasis to skin--carcinoma hemorrhagiectoides--has also been observed in a woman with breast cancer ,3,19.Carcinoma erysipelatoides also referred to as inflammatory metastatic carcinoma, mimics erysipelas which is an acute streptococcal infection of the skin. Similar to the women in this report, carcinoma erysipelatoides can occur as the sole skin manifestation of cutaneous metastatic breast cancer, or it can appear with other skin patterns of metastatic cancer, such as carcinoma en cuirasse. The cellulitis-mimicking cutaneous metastasis most commonly appears at the prior site of the primary tumor as an erythematous patch and/or plaque with well-defined margins. Pathology shows infiltration of tumor aggregates predominantly in the superficial dermal lymphatic vessels resulting in their obstruction; however, to a lesser degree, the cancer cells can not only be present in the dermal blood vessels but also sparsely infiltrate the dermis. Therefore, the affected skin may also have a peau d’orange (orange peel) appearance--masquerading as an infectious process--resulting from localized lymphedema caused by the blockage of lymphatics by the cancer cell thrombi ,3.Carcinoma hemorrhagiectoides is a recently observed pattern of cutaneous metastasis in a breast cancer patient. It typically presents as large, violaceous, confluent, hemorrhagic, and erythematous dermal plaques across the chest from the neck to the abdomen; in some patients, their carcinoma hemorrhagiectoides cutaneous metastases have been described as a shield sign since the presentation of the skin metastasis is reminiscent of a Medieval knight’s shield. In addition, metastatic skin lesions of carcinoma hemorrhagiectoides can also mimic angiokeratomas within the plaques. Pathology shows not only extensive infiltration of the dermis by tumor cells but also endothelial-lined vessels of lymphatic and/or blood origin containing cancer cells. Also, there is hemorrhage of the erythrocytes into the tumor-filled lymph vessels .A 90-year-old woman presented with carcinoma hemorrhagiectoides which appeared as a hot, erythematous, indurated and infiltrated, raised plaque on the left chest wall and breast that extended to her left shoulder, arm, and scapula. Radiologic workup discovered extensive lymph node disease; she also had a markedly elevated lactate dehydrogenase of 1178 international units per liter . A skin biopsy demonstrated interconnecting cords and nests of tumor cells in the dermis and subcutaneous tissue; neoplastic cells were also present in the lumina of some of the lymphatic vessels in the superficial dermis. The patient and her family refused any treatment for her metastatic breast cancer; she died six weeks later .Carcinoma telangiectoides appear as red and purple patches and papules usually located on the chest wall; prominent telangiectasias are also typically present. The lesions can mimic those of lymphangioma circumscripta. Pathology shows dilated blood vessels (resulting in the violaceous hue of the lesions) containing tumor cells. The dermis can also be sparsely populated with cancer cells ,3.Carcinoma en cuirasse is breast cancer cutaneous metastases that mimic scleroderma. The terminology refers to a cuirassier, who is a cavalry soldier, wearing a cuirass. The cuirass is the fastened-together metal breast and backplate that covers the torso. Cuirass, derived from the French word cuirace (meaning leather), describes the material originally used to make the armor ,3.The morphea-like lesions of carcinoma en cuirasse appear as bound-down, flesh-to-red colored scleroderma indurated dermal plaques. Similar to the woman in this report, the lesions can become crusted, ulcerated, or both. Pathology typically shows a linear distribution of single cancer cells between the collagen bundles in the fibrotic dermis ,3.In addition to benign-appearing lesions , breast cancer cutaneous metastases can mimic benign cutaneous neoplasms such as cysts, dermatofibromas, or milia-en-plaque ,5,6. CysA 68-year-old woman presented with eight-firm brown nodules on her upper back that were suspected to be multiple dermatofibromas; her breast cancer had been treated 26 years earlier. A skin biopsy demonstrated cutaneous metastases of breast origin; her cancer antigen (CA) 15-3 tumor marker was elevated at 426 units per milliliter, but the remainder of her malignancy workup was negative. All the skin lesions disappeared, and her CA 15-3 was negative within 12 months after starting treatment with letrozole [Cutaneous metastases of breast cancer presented as milia-en-plaque on the right breast of a 39-year-old woman whose inflammatory-type infiltrating pleomorphic lobular carcinoma of the left breast with bone metastases had been diagnosed during her pregnancy two years earlier. The cancer was treated with chemotherapy , surgery (left mastectomy), and radiotherapy. She was receiving trastuzumab when the new skin lesions appeared; in addition to indurated plaques on her sternum and left chest, milia-like papules that resembled mila-en-plaque developed on the undersurface of her right breast. Skin biopsies from the sternum and right breast both showed islands and microthrombi of tumor cells in the dermis; there were no keratin cysts. The subsequent evaluation did not find metastases in the right breast or viscera; the cutaneous lesions were treated with additional radiation therapy, and she was maintained on the trastuzumab .A collision tumor refers to the pathologic presence of two or more benign neoplasms, malignant cancers, or both either juxtaposed or intermingled in the same skin site. Recently, the collision tumor has been renamed as multiple skin neoplasms at one site (MUSK IN A NEST). Two women had breast cancer cutaneous metastases that presented as multiple skin neoplasms at one site: congenital melanocytic nevus and metastatic breast carcinoma ,4.A 44-year-old woman presented with a right breast 13 x 8-centimeter fungating tumor of one-year duration that had ulcerated three months earlier; adjacent to the tumor, two non-pigmented nodules (of which the larger was six millimeters) were observed. A right modified radical mastectomy was performed, revealing infiltrating poorly differentiated ductal breast carcinoma involving the nipple skin and all breast quadrants. Metastatic adenocarcinoma was present in the axillary lymph nodes; additional workup revealed liver and bone metastases. Biopsy of the skin nodules showed intradermal nevi; one of the nevi also showed nests of adenocarcinoma cells not only amongst the nevus cells but also in other areas of the dermis and dermal lymphatics [The second patient with multiple skin neoplasms at one site consisting of breast cancer cutaneous metastases and intradermal nevus was a 76-year-old woman with a prior history of breast cancer who presented with a left breast ulcerated mass and a pigmented skin nodule of the upper left chest. The ulcerated breast tumor showed an S-100 negative, cytokine-positive atypical anaplastic tumor consistent with metastatic breast adenocarcinoma. The pigmented skin nodule showed a dermal nevus consisting of S-100 positive, cytokeratin-negative melanocytes in the upper dermis that merged into cords and aggregates of metastatic breast cancer in the deeper dermis .Breast cancer cutaneous metastases can also mimic primary cutaneous malignancies. Breast carcinoma of the inframammary crease can masquerade as a primary basal cell carcinoma or squamous cell carcinoma . In addiA 40-year-old woman was diagnosed with infiltrating ductal carcinoma of the right breast; she had a modified radical mastectomy, and there was no tumor in the axillary nodes. Bone metastases of the left seventh rib were discovered six months later; she received chemotherapy for two years, and they disappeared. They again appeared in the same rib six months after stopping therapy, and she was treated with radiotherapy. Subsequently, three and a half years later, a 7-millimeter brown nodule with irregular borders appeared on the left side of her forehead; the clinical differential diagnosis was melanoma and pigmented basal cell carcinoma. An excisional biopsy was performed. Cutaneous metastatic carcinoma of the breast was demonstrated; the cytoplasm of many of the tumor cells contained large amounts of melanin. Additional patients have also been described with pigmented breast cancer cutaneous metastases on their mastectomy scar or scalp that mimicked a melanoma [Cutaneous breast cancer metastases can mimic bacterial and viral infections. In addition to carcinoma erysipelatoides, bacterial infections mimicked by breast cancer skin metastases include folliculitis. Varicella-zoster virus infection can also be mimicked, presenting as zosteriform metastases, by breast carcinoma spreading to the skin -3,9,10.Folliculotropic cutaneous breast cancer metastases can mimic folliculitis. They presented as painless, non-pruritic, the diffuse pustular-like eruption of four months duration on an erythematous base of the deltoid region of a 51-year-old woman’s right arm who five years earlier had an adenocarcinoma of the breast excised. The lesions, during the patient’s initial evaluation, were determined to be folliculitis. She was treated with topical and systemic antibiotics. When there was no improvement, a biopsy was performed that established the correct diagnosis of folliculotropic metastatic breast carcinoma .Zosteriform metastases describe breast cancer-related skin lesions that are indurated, flesh-colored to red to violaceous, papular, nodular, or pseudo-vesicular and appear in a dermatomal distribution. Similar to the woman in this report, the zosteriform cutaneous metastases can also be crusted or ulcerated. The most common sites affected are the chest and abdominal wall. Although the lesions may be asymptomatic, they can also be painful and thereby result in the patient being treated for herpes zoster virus infection with antiviral therapy before establishing the correct diagnosis ,3,10.The cutaneous metastases occur in previously normal skin for some of the patients. However, in other individuals, a prior herpes zoster infection at the location created an immunocompromised cutaneous district that became more susceptible to the subsequent development of lesions at that site. In contrast to varicella-zoster virus-associated lesions, the zosteriform skin metastases may not only occupy more than two to three adjacent dermatomes but also be bilateral ,3,10.Several miscellaneous presentations of breast cancer cutaneous metastases have been observed. Similar to the woman with carcinoma en curiasse and zosteriform metastases in this report, the erosive skin metastases can be localized; however, other women have presented with erosive cutaneous metastatic breast cancer that was extensive . NodularRarely, women with breast cancer develop clown nose-like cutaneous metastases. This was initially described as diffuse infiltration of the nasal tip; however, the presentation of clown nose skin metastasis has expanded to include exophytic lesions on the tip of the nose. Subsequently, clown nose-like lesions have been observed not only in metastatic visceral tumors (most commonly lung cancer) but also in genetic syndromes  and primary diseases involving the nasal tip .A 74-year-old woman presented with reddish infiltration of the distal part of her nose of three months duration. Five months earlier, she had the removal of her left breast because of cancer. Two months later, she developed a sharply demarcated red infiltration of the nasal tip; palpation of the affected area was painless but very coarse. Biopsy showed metastatic breast carcinoma in the deep dermis and subcutaneous fat extending to the cartilage. Workup did not reveal visceral metastases, and the solitary nasal tip metastasis was excised; however, six months later, she developed brain metastases and died. The investigators emphasized that the coarse consistency of their patient’s nose might be an important indicator of the underlying neoplastic process .Paget’s disease is a primary intraductal mammary carcinoma. However, metastatic breast cancer can also mimic Paget’s disease. In some of these patients, the lesions are pigmented and mimic melanoma . In addiPapillomatosis cutis lymphostatica  is an uncommon asymptomatic manifestation of either primary (hereditary) lymphedema or secondary (acquired) lymphedema; the latter is associated with damaged lymphatics, such as in patients with diabetes. Albeit uncommon, papillomatosis cutis lymphostatica has been observed following iatrogenic secondary lymphedema. Clinically, hyperkeratotic, verrucous, and papillomatous lesions typically develop on the distal aspect of the lymphedematous extremity .Breast cancer cutaneous metastases masquerading as papillomatosis cutis lymphostatica were the initial presentation of recurrent neoplastic disease. A 60-year-old woman developed multiple painless non-confluent oval red nodules that mimicked papillomatosis cutis lymphostatica on the volar aspect of her lymphedematous left arm and forearm. She had a complete mastectomy (without reconstruction) and axillary lymph node dissection one year earlier as the initial treatment of invasive lobular left breast carcinoma; this was followed by local radiotherapy, adjuvant chemotherapy, and currently letrozole hormonal therapy. A skin biopsy was performed since the cutaneous lesions had increased in diffusion and redness during two months of physiotherapy with bandages and plastic devices. The biopsy showed metastasis of invasive breast carcinoma in the dermis and subcutaneous fat .Targetoid breast cancer cutaneous metastases have also been observed. The 54-year-old woman with skin metastases in her radiation therapy port had a targetoid metastasis of her left breast carcinoma. The macular metastasis on the ipsilateral chest presented as an erythematous ring with a white central area Figures .Metastatic breast cancer presented with targetoid-appearing cutaneous lesions appearing as annular plaques that had depressed hyperpigmented centers in a 40-year-old woman; six months earlier, she had surgery for right breast carcinoma. Examination demonstrated not only a lump on the right breast under the postoperative scar but also papulonodules and targetoid plaques over the right breast and inframammary regions. Fine needle aspiration cytology of a lymph node was suggestive of metastatic breast carcinoma, and biopsy of a skin lesion showed nests of tumor cells .Erythematous breast cancer cutaneous metastases can also masquerade as reactive erythema. Similar to the 54-year-old woman in this report whose skin lesions of metastatic breast carcinoma were in the radiation therapy port, skin metastases can present as confluent erythematous macules that are annular or have irregular-shaped borders. In addition, they can mimic urticaria or erythema annulare centrifugum ,14,15.Breast cancer cutaneous metastases--the initial presentation in a previously cancer-free woman--appeared as urticaria on the upper half of the body of a 75-year-old woman. Three months earlier, she had noted the sudden onset of numerous painless, non-pruritic, firm, red, five-millimeter, dermal plaques that were initially considered to be wheals; however, in contrast to bona fide urticaria, the asymptomatic lesions were stable in size and location. A biopsy of the skin lesions showed tumor cells, suggestive of breast cancer, infiltrating the dermis. Subsequent work-up discovered invasive lobular right breast carcinoma--positive for estrogen receptor, progesterone receptor, and HER2--with metastases to bilateral axillary lymph nodes, liver, and bones .Erythema annulare centrifugum is gyrate erythema that typically presents on the trunk and proximal extremities as annular or arcuate patches with an advancing peripheral border and central clearing; at the trailing edge of the erythema, scaling is often present. Erythema annulare centrifugum can be idiopathic; however, it has been associated with multiple conditions including bullous dermatoses (such as pemphigus vulgaris), foods, endocrine disorders (such as Graves’ disease), infections , and medications . Cancer -associated variant of this reactive erythema has been observed as a malignancy-related condition in patients with breast carcinoma who develop paraneoplastic erythema annulare centrifugum eruption (PEACE). Although the skin lesion of PEACE does not demonstrate cutaneous metastases of breast cancer in the dermis, the appearance of erythema annulare centrifugum correlates with the discovery or recurrence of breast cancer in these oncology patients .Cutaneous metastases of inflammatory breast cancer mimicking erythema annulare centrifugum were the presentation of locally recurrent breast carcinoma in a 38-year-old woman. She presented with several enlarging, annular, erythematous macules with central clearing on the back for which the clinical diagnoses of erythema annulare centrifugum and subacute cutaneous lupus erythematosus were considered. Five years earlier, she had been diagnosed with metastatic invasive ductal right breast carcinoma  involving the dermal lymphatics and lymph nodes. She was treated with chemotherapy, surgery, and radiotherapy. However, 40 months later, she developed inflammatory carcinoma of the left breast with dermal lymphatic and lymph node metastases; surgery was followed by additional chemotherapy and localized radiotherapy. Her new back lesions appeared after completing treatment. Biopsy of the skin lesions showed invasive ductal carcinoma not only in the superficial dermis but also within the lymphatic vessels. At least five additional patients whose locally recurrent cancer presented with metastasis of inflammatory breast carcinoma mimicking erythema annular centrifugum have also been described .Several skin conditions can be mimicked by breast cancer cutaneous metastases. Carcinoma en cuirasse skin metastases from breast cancer can masquerade as scleroderma. In addition, metastatic breast cancer can mimic alopecia areata, dermatitis, and hidradenitis suppurativa -4,16,17.Scalp hair loss caused by cancer is referred to as alopecia neoplastic; it can be primary  or secondary . Alopecia-associated with breast cancer cutaneous metastases typically presents as patches of absent hair; however, in some individuals, nodules may also be present in the area of alopecia. In some of the breast cancer patients, the cancer-associated hair loss mimics alopecia areata; in other patients with carcinoma of the breast, the neoplasm-related alopecia appears similar to that observed in either discoid lupus erythematosus, lichen planopilaris, morpheaform basal cell carcinoma, or pseudopelade ,3,16.Breast cancer cutaneous metastases can mimic dermatitis. Cutaneous metastases located in the skin fold beneath the breasts can masquerade as eczema ,3,4. TheA breast cancer cutaneous metastasis that masqueraded as dermatitis and vasculitis was the initial presentation of unsuspected breast carcinoma in a 66-year-old man. The skin lesion, on his left leg for the prior one year, had been clinically diagnosed as dermatitis and vasculitis; he had been unsuccessfully treated with radix salviae miltiorrhizae , other oral medications  and topical corticosteroids. Cutaneous examination of the affected site demonstrated a large solitary erythematous area of nonpitting edema occupying the left buttock and posterior thigh; biopsy of presumptive dermatitis and vasculitis lesion showed metastatic carcinoma in the lymphatic vessels. Subsequently, a thorough clinical evaluation detected not only a previously undiagnosed two-centimeter left breast subareolar mass, but also a swollen lymph node in both the axilla and the groin; lumpectomy of the left breast showed an intraductal carcinoma .Hidradenitis suppurativa is a chronic inflammatory condition that typically presents in the axilla, groin, buttocks, and body fold such as the inframammary creases and chest; lesions appear as tender red nodules and abscesses with fistulas and sinuses. Cutaneous metastatic right breast adenocarcinoma masquerading as hidradenitis suppurativa was the initial manifestation of undiagnosed cancer; it presented as an enlarging red nodule that did not respond to oral and topical therapy for hidradenitis suppurativa in a 30-year-old woman. The woman had draining sinus tracts and skin nodules of seven months duration affecting her axilla, groin, chest, and breasts; a clinical diagnosis of hidradenitis suppurativa was established, and she was treated daily with oral minocycline (100 milligrams) and topical five percent benzoyl peroxide wash and one percent clindamycin solution. At her three-month follow-up visit, all of the skin lesions had resolved except a right breast nodule that had become larger; a biopsy of the nodule showed breast adenocarcinoma .The ipsilateral chest wall and breast  are the most frequent sites of cutaneous breast carcinoma metastases -3. HowevIn addition to carcinoma telangiectoides (mimicking lymphangioma circumscripta) and carcinoma hemorrhagiectoides (mimicking angiokeratomas), breast cancer skin lesions can also masquerade as other vascular lesions. This includes purpura mimicking vasculitis. It also includes skin metastases that appear similar in morphology to benign and malignant vascular neoplasms, such as pyogenic granuloma and angiosarcoma ,3,18-20.A 67-year-old man presented with an easily bleeding, centrally eroded, reddish nodule adjacent to the mastectomy scar on his right chest of four months duration; dermoscopy suggested that the nodule was a hypervascular lesion and the clinical impression was a pyogenic granuloma. Seven years earlier, he had been diagnosed with T2N0M0 papillary right breast carcinoma that was positive for estrogen receptor and progesterone receptor and negative for HER2. He achieved a complete remission following surgery and five years of tamoxifen. The new nodule was excised; pathology showed tubular-glandular structures and aggregates of papillary breast carcinoma that diffusely infiltrated the dermis and subcutaneous fat .Women with either carcinoma erysipelatoides or carcinoma telangiectoides have developed breast cancer cutaneous metastases that mimic primary cutaneous angiosarcoma. A 64-year-old woman presented with a large, indurated, red-purplish plaque--clinically suggestive of angiosarcoma--on the left side of her face, neck, and upper back of four years duration; nine years previously, she had been diagnosed with invasive ductal and lobular left breast carcinoma with bilateral axillary metastases that were treated--resulting in a complete clinical response--with surgery, radiation therapy, and chemotherapy. Biopsy of her skin lesion showed breast carcinoma cell emboli only occupying the dermal lymphatic vessel lumen, without any extravasation of tumor cells into the dermis, consistent with carcinoma erysipelatoides .A 53-year-old woman presented with painful erythema and accompanying pronounced telangiectasia--clinically suggestive of angiosarcoma--extending from the vertex of her scalp  onto the forehead, nose, and cheeks of one-month duration; eight years previously, she had been diagnosed with ductal right breast carcinoma with metastasis in one of eight axillary lymph nodes and was treated--without subsequent clinical or mammographic recurrence until five months earlier--with wide local excision, radiotherapy, chemotherapy, and five years of tamoxifen. Biopsy of the skin lesion showed breast carcinoma tumor aggregates admixed with thrombus cell emboli plugging ectatic blood vessels throughout the dermis, without any extravasation of tumor cells into the dermis, consistent with carcinoma telangiectoides .Breast cancer cutaneous metastasis most often occurs in oncology patients as a manifestation of persistent or recurrent neoplastic disease. However, less often, they can be the first indication of extranodal metastases in a person with established cancer or the initial presentation of breast carcinoma in a previously undiagnosed individual. The morphology of metastatic breast cancer skin lesions is variable. The pleomorphic skin lesions can have unique locations, and they can mimic benign cutaneous lesions and tumors, cutaneous malignancies, infections, reactive erythema, skin conditions, vascular lesions, and other miscellaneous conditions. A skin biopsy is necessary to confirm the diagnosis of breast cancer cutaneous metastasis. Therefore, especially in a patient with breast cancer and possibly in a cancer-free individual, biopsy should be considered for the evaluation of a new and/or a treatment-unresponsive cutaneous lesion.