Abstract
Background
Vascular malformations are rare diseases that are best managed in multidisciplinary vascular anomaly centers (VAC). So far, there are few published data on the logistic structure, patient allotment, and internal workflow in an interdisciplinary VAC.
Purpose
To demonstrate the referral structure and patient allotment in a European VAC.
Material and Methods
A retrospective cohort study was conducted. All patients treated in the VAC since its establishment in April 2014 until June 2020 were identified. A total of 461 patients were included in this study.
Results
Most often, a venous malformation was diagnosed (49.9%), followed by arteriovenous malformations (8.7%) and syndromal vascular malformations (8.2%). Only 45.1% of referral diagnoses were correct. Of referrals, 35.1% were internal on-campus references, 28.0% were external references through physicians in private practice, and 19.7% came via external cooperating hospitals. Of the patients, 17.1% were self-admissions without a referral.
Conclusion
The most important referring clinics are internal medicine, pediatric, and vascular surgery. A substantial proportion of referrals came from private practices. Recruiting these cooperation partners should be considered a high priority when establishing a new VAC. The rate of misdiagnosis is high, and more education of fellow clinicians is urgently needed. Therefore, patients with vascular malformations should be referred to and treated in dedicated centers for vascular anomalies.
Keywords
Introduction
Vascular anomalies are a rare disease, classified into vascular tumors and vascular malformations according to the ISSVA nomenclature (1,2). Vascular malformations are highly heterogenic and characterized by complex clinical phenotypes and can range from small non-symptomatic lesions to large debilitating malformations. These congenital disorders can be symptomatic at a young age or remain quiescent until adulthood. In consequence, patients of all ages may be affected with various manifestations.
The complex treatment needed for these patients is best provided in an interdisciplinary center with clinicians from many fields (3), including diagnostic and interventional radiologists, hematologists, plastic surgeons, vascular surgeons, craniomaxillofacial surgeons, pediatric surgeons, angiologists, pediatricians, and so on. Patients with vascular anomalies should be referred to dedicated centers for diagnostics and therapy. Yet, awareness for these centers must be intensified to provide time-sensitive patient care and avoid deterioration of the clinical condition.
So far there is only few published data on the logistic structure, patient allotment, and internal workflow in an interdisciplinary vascular anomaly center (VAC). For Germany, in particular, no data related to these subjects are available. Being familiar with our multidisciplinary approach to vascular anomalies, we aim to publish our seven years of experience in Germany in this study. The aim of the present study was to analyze potential changes of the spectrum of diagnoses, referral characteristics, and treatment modalities over time since the establishment of the VAC. This may aid in raising awareness for VACs and thus help to improve quality of diagnostic and therapeutic patient care. The German healthcare system may be compared to most healthcare systems in high-income countries. Consequently, the presented findings may be of interest to a broad audience.
Material and Methods
Based on a retrospective chart review, all patients referred to and treated at the Anomaly Center of the Mannheim University Medical Center since its establishment in April 2014 until June 2020 were identified. The patients were allocated to groups according to the year of their first physical outpatient consultation.
A retrospective cohort study was designed to investigate changes in the referral structure since establishment of the VAC. In total, 461 patients were identified and included in this study. All reported data in this manuscript are based on medical information that has been derived from clinical consultation and treatment of patients. In the University Medical Center of Mannheim, the interdisciplinary center for vascular anomalies comprises interventional radiologists, reconstructive plastic surgeons, gynecologists, vascular, pediatric and orthopedic surgeons, angiologists, otorhinolaryngologists, dermatologists, and pathologists. Specialists of other fields, for example human genetics and paramedical disciplines such as physiotherapy, are regularly consulted, if needed. Patients are presented from departments within the Mannheim University Medical Center, but are frequently referred from external hospitals and, in increasing number, by physicians in private practice. In addition, an increasing number of patient self-referral can be observed, meaning patients that book appointments directly with our institution without referral from another physician. There are monthly meetings, where patient cases are discussed and treatment plans are formulated. The results of these team meetings are protocolized and sent to all cooperation partners. The follow-up is then organized by the referring or best suited specialty.
No further interview or contact was conducted for this study. No third parties had access to any patient-related data during the conduction of this study and all data that were stored were previously anonymized. The study was approved by the local ethics committee (ID-Nr. 2016-522N-MA).
In the review of the patient charts and the electronic inpatient hospital system, we captured the following factors: patient demographics, such as sex, age, duration of travel time and distance to reach the VAC, frequency of pre-VAC medical consultations regarding the vascular anomaly, outpatient referral diagnosis, localization and distribution of the vascular malformation, referring medical specialty, past diagnostic measures and previous therapies, such as screening for coagulopathy, biopsy, ultrasound, CT or MRI scans, intervention, and surgical resection. All diagnostic procedures, interventions for diagnosis and therapy, referral to associated specialties within the VAC, complications during treatment in the VAC, and the final diagnosis were extracted.
Statistical methods
Normally distributed data were analyzed with the Student t-test. For not normally distributed data, the Mann–Whitney U test was applied. The chi-square test was used for categorical variables. Correlation analysis was performed using the Spearman non-parametric correlation test. Categorical variables are presented with frequencies (percentages) and continuous variables with means ± standard deviation (SD) or median (range). Statistical significance was defined as P < 0.05. Data were analyzed using the GraphPad Prism Version 9.0.2 for Mac (GraphPad Software, San Diego, CA, USA).
Results
Patient demographics and spectrum of disease
A total of 461 patients (57.5% female patients, 42.5% male patients; mean age = 26.4 years; age range = 14 days to 82.2 years) were included in this study. The mean travelling distance to reach the VAC was 92.3 ± 254.5 km. The patient demographics are depicted in Table 1, and Fig. 1 illustrates the travelling distances. There were no significant differences in the distance to the VAC destination when comparing the different vascular anomaly entities. Fig. 2 depicts the travelling distances across the years. There was a significant correlation of the number of regional and national patients with the time passed since establishment of the VAC (regional: Spearman correlation coefficient r = 0.91, P < 0.01 and national: r = 0.78, P = 0.04).
Geographical travel distance to the vascular anomaly center. Local: 0–20 km; regional: 21–150 km; national: >150 km; international: patients arriving from countries other than Germany.
Travel distance by year. On the x axis, the years are plotted and on the y axis, the number of patients. Local: 0–20 km; regional: 21–150 km; national: >150 km; international: patients arriving from countries other than Germany.
Patient characteristics.
Values are given as n (%) or median (range).
FAVA, fibro-adipose vascular anomaly; VMCM, multiple cutaneous and mucosal venous malformations.
In most patients, a venous malformation was diagnosed (49.9%), followed by arteriovenous malformations (8.7%) and syndromal vascular malformations (8.2%), such as Klippel-Trénaunay syndrome. Hemangiomas comprised 6.7% of all referrals. The second most common cause for referral to the VAC after venous malformations was the diagnosis “non-vascular anomaly related vessel disorder or soft tissue tumor of unknown etiology” (9.5%). Only 45.1% of referral diagnoses were correct.
Most commonly the lower extremities (52%) were involved, followed by the upper extremities (31.7%), head and neck area (20.6%), trunk (11.3%), thorax (10%), and pelvis (5.4%). The majority of patients had a singular lesion (86.1%).
There was a significant correlation of the yearly number of patients with lymphatic malformations with the elapsed time since the establishment of the VAC (Spearman correlation coefficient = 0.87; P = 0.02). The incidence of other entities did not significantly correlate with the elapsed time since the establishment of the VAC. Fig. 3 demonstrates the diagnoses, listed according to the years.
Yearly incidence in our vascular anomaly center, divided by entity. LM, lymphatic malformation; AVM, arteriovenous malformation; VM, venous malformation.
Referring specialties
The majority of referrals were from the department of internal medicine (n = 90, 23.6%), followed by pediatric surgery (n = 74, 19.4%) and vascular surgery (n = 45, 11.8%). The pediatric department (n = 36, 9.4%) and the clinic for trauma and orthopedic surgery (n = 33, 8.6%) also contributed to the patient referral. Patient allotment was also managed by general surgery (n = 25, 6.5%), diagnostic radiology (n = 19, 4.9%), dermatology (n = 15, 3.9%), plastic surgery (n = 14, 3.7%), and otorhinolaryngology (n = 13, 3.4%). Other referring specialties accounted for the remaining 18 (4.7%) referrals. The referring specialties are illustrated in Fig. 4. The origin of all the above-mentioned referrals was as follows: 35.1% were internal on campus references from our institution; 28.0% were external references through physicians in private practice; and 19.7% were via external cooperating hospitals. In addition, 79 (17.1%) patients visited the VAC independently, without being actively referred from an inpatient or outpatient institution.
Total number of referrals divided by specialty. Not shown are 79 patients who self-administered themselves without prior referral.
Spectrum of patient allotment over the seven-year period
The development of the patient allotment structure to our VAC in Germany shows an increase of referrals from external clinically cooperating partners, from hospitals as well as private practices. The number of referrals from external sources correlated strongly with the time passed since the establishment of the VAC (correlation coefficients: external hospitals: 0.93, P < 0.01; private practices: 0.82, P = 0.03). These correlations were statistically significant. A correlation was also to be seen for the number of self-referrals of patients without involvement of referring clinics or hospitals from the time since the establishment of the VAC (correlation coefficient: 0.75), although no significance could be achieved here statistically (P = 0.06). The number of internal referrals did not correlate with the period of establishment of the VAC (correlation coefficient: 0.11, P = 0.84). The results are depicted in Fig. 5.
Yearly referrals divided by referring origin.
Discussion
The dedicated vascular anomaly center at the Mannheim University Medical Center was established in April 2014. This hospital is a center of tertiary care for a major population in Germany.
Multidisciplinary team meetings (MDTM) have been successfully implemented for many types of cancer and are likely to improve the oncological outcome, for example in colorectal cancer (4,5). They have also been established for rare types of cancer or rare diseases (6,7). In our opinion, MDTMs with their well-established workflows play a crucial role in high-quality care for patients experiencing rare diseases. This is especially true for vascular anomalies that have numerous interdisciplinary overlaps. These MDTMs require interdisciplinary cooperation with experienced partners. The often-frequented arduous patient odysseys with multiple appointments with different doctors and specialties, leading to a delay of correct diagnostics and treatment, may be averted by such MDTMs. Therefore, regular MDTMs with postprocedural care should be demanded for patients experiencing vascular anomalies.
In the present study, we have outlined the referral characteristics to a dedicated VAC in Germany since its establishment in 2014. In total, 461 patients have been treated from April 2014 until June 2020.
Compared to the current literature, we had a rather small number of vascular tumors in our cohort (8,9). Simple congenital and occasionally infantile hemangiomas had initially been monitored and treated in the VAC. However, as a consequence of an increasing case load, patients with potential hemangiomas, commonly affecting neonates and infants, were reviewed in the VAC but then referred back to the pediatric department for treatment and follow-up, especially in cases with infantile hemangiomas, requiring weight adapted propranolol therapy (10). As hemangiomas represent the most frequent and best-known vascular tumors (11) among many clinical disciplines, including pediatrics and dermatology, they can indeed be well monitored outside a VAC. The VAC should provide council in complex cases or offer dedicated interventional or surgical therapy in patients that cannot be managed conservatively. These findings might explain the comparatively low number and proportion of hemangiomas in our cohort.
The number of patients presenting with capillary and lymphatic malformations is rather low in our study, but comparable to the results presented by Ng et al., who reported data from a Hongkong VAC (12). This may be related to the fact that these vascular anomalies are not as frequent as venous malformations and have fewer indications for immediate interventional or surgical therapy compared to symptomatic, debilitating venous or arteriovenous malformations.
The low frequency of correct referral diagnosis (45.1%) is consistent with previous studies. Greene et al. reported a rate of correct diagnosis of 53% in a large series of 5621 patients, Mattila et al. stated that only 38% of patients with vascular malformations had a correct referral diagnosis (8,9). Ng et al. stated that only 32% of patients were referred to a VAC with a correct diagnosis (12). In a further publication, Mathes et al. presented a rate of correct referral diagnosis in 22% (13). These results underline the persistent difficulties of physicians to correctly diagnose a rare disease like vascular malformations and tumors. Hassanein et al. confirmed this finding in 2010, reporting that even in the scientific literature with expected technical terms and classification system, the word “hemangioma” was used for the description of any kind of vascular malformation (14). Moreover, in cases where clinical, radiological, and pathology reports were present, Pahl et al. realized that only 9% of the diagnoses were in agreement in the final diagnosis determined in their interdisciplinary VAC (15).
The responsibilities of the VAC include confirmation of diagnosis in cases of vascular anomalies and detection of other entities like vascular tumors with borderline and malignant findings that require other therapeutic options (16). In addition, the assessment of soft tissue tumors in, for example vasculitis, has to be considered (17,18). One out of ten patients referred to our VAC did not suffer from a vascular malformation or tumor, but from an unrelated disease. Similar numbers have been reported by the scientific community.
Over the years, the number of patients being referred to our VAC from external institutions has increased significantly (P < 0.01). This is to be expected, as patient recruitment, precise diagnosis as well as therapy and transfer of interdisciplinary knowledge for the sake of dedicated patient care, require time. In this process, the regional clinical and scientific reputation of a dedicated VAC may achieve national and international acceptance. This process is also shown in the significant correlation of travel distance (regional P < 0.01 and national P = 0.04) and the elapsed time since establishing the VAC.
In total, 64.8% of patients were referred to us from external, off-campus clinical facilities. In a comparable analysis, Mathes et al. described that 58% of their patients were referred from external clinical sources (13).
There was a substantial number of referrals from private practices (28.0%), underlying the importance of close cooperations not only with other hospitals, but also with general practitioners and other physicians in private practice. The most referrals from within our campus came from the departments of internal medicine, pediatric surgery, and vascular surgery. There were only slight changes in the referral characteristics when examining the development over a seven-year period.
The findings presented in this retrospective study may provide guidance for emerging VACs. Besides information on the initially most relevant clinical disciplines to join the interdisciplinary team, the process of patient recruitment and surveillance is described and the need for specialized clinicians to take care of a rare disease. This process requires solid funding. Dedicated treatment and patient care in the long term will benefit from increasing growth of the VAC and financial sustainability at an early stage. Straughan et al. have published data that a financially sustainable management of a VAC is feasible (19). There is a vast number of patients with vascular anomalies. Yet, the existing number of VACs worldwide is not sufficient to attend to all patients affected and seeking therapy. Since more dedicated centers for the treatment of vascular anomalies are needed, the above-mentioned factors might prove useful for fellow clinicians seeking to open a new or expand an existing VAC.
The present study has some limitations. First, there is the retrospective nature of our study design. Furthermore, many laboratory findings have not been documented initially and are thus not available for analysis. Naturally, the patient cohort is very heterogenous with many different affected sites and a large spectrum of disease. However, this is inherent to vascular malformations and even in this very large collective, these issues cannot be circumvented.
In conclusion, we have shown that the most important referrals clinics are internal medicine, pediatric surgery, and vascular surgery. A substantial proportion of referrals came from private practices. Recruiting these cooperation partners should be considered as a high priority, when establishing a new vascular anomalies center. The rate of misdiagnosis among the referred patients is still very high and more education of fellow clinicians is urgently needed. Therefore, patients with vascular malformations should be referred to and treated in dedicated centers for vascular anomalies.
Footnotes
Declaration of conflicting interests
The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding
The author(s) received no financial support for the research, authorship, and/or publication of this article.
