Management Of Carotid Body Tumors Research Articles

The "INT-EX Technique": Internal to External Approach in Carotid Body Tumour Surgery.

Carotid body tumours are rare and mostly benign neoplasm. They are slow growing but can evade or exert pressure on neighbouring important neurovascular structures. Hence, surgical resection remains the treatment modality of choice for large tumours partially or completely encasing the carotid arteries. But the surgical resection of these tumours with minimum morbidity is challenging because of their highly vascular nature. Earlier literature has dealt with various aspects of management of carotid body tumours including classification, morbidity, work-up, embolisation and extent of resection. However, the options in techniques of dissection for carotid body tumours have not been elaborated much. Here, we describe a stepwise dissection technique of carotid body tumours from the internal carotid towards the external carotid artery. This surgical technique, named as "the internal to external (INT-EX) technique", provides better control of bleeding during the surgery, ease of dissection and lesser post-operative morbidity.

Current surgical management of carotid body tumors

BackgroundCarotid body tumors (CBTs) are rare. Management guidelines may include genetic testing for succinate dehydrogenase (SDH) mutations. We performed an institutional review of the surgical management of CBT. MethodsA retrospective analysis (1994-2015) of CBT excisions at our institution was performed. Data obtained included demographics, genetic testing (if performed), intraoperative details, postoperative morbidity, and long-term outcomes. Data from the first CBT excision were included in patients with bilateral tumors. Genetic testing was routinely offered in patients with a family history of CBT or multiple paragangliomas. ResultsA total of 183 CBTs (124 female [67.7%]) were excised. A neck mass was present in 106 patients (57.9%), 24 patients (12.1%) presented with tenderness or neck pain, and 3 (1.6%) presented with cranial nerve dysfunction. Computed tomography (57.9%) or magnetic resonance imaging (51.3%) were the most commonly used imaging modalities. Preoperative angiography was performed in 73 patients (39.8%), and 62 of them (84.5%) underwent embolization or internal carotid balloon occlusion testing, or both. Mean tumor diameter was 3.2 cm (range, 0.6-7.2 cm). There were 71 (38.8%), 75 (41%), and 37 (20.2%) Shamblin type 1, 2, and 3 tumors, respectively. Average operating time was 224 minutes (range, 52-696 minutes). Average blood loss was 143.9 mL (range, 10-2000 mL). Arterial reconstruction with an interposition graft was required in 10, and patch angioplasty was performed in four. Cranial nerve injury was permanent in 10 (5.5%), and the rate of stroke was 1% (n = 2). A total of 382 lymph nodes were excised, and all were benign. There were no deaths ≤30 days. Only one patient presented with malignant disease 2 years after CBT excision, and this patient did not undergo genetic testing. Thirty-four (18.6%) had a family history of CBT. SDH testing was performed in 18 patients, and 17 tested positive. Positive genetic testing had a correlation with earlier age at operation (P < .0001). Mean age at diagnosis of patients with SDH mutations was 38.0 years, and patients without known SDH mutations presented at a mean age of 50.3 years. In patients with SDH mutations, tumor diameter, operating time, blood loss, and distribution of Shamblin type 1, 2, and 3 lesions were not significantly different compared with the control group. ConclusionsCBT can be treated with minimal morbidity and mortality; however, the subgroup of patients with positive SDH mutations may represent a variant group of younger patients. Vascular surgeons should be aware of genetic testing to identify patients and family members who should undergo additional preoperative testing and monitoring for other paragangliomas. Concomitant lymph node dissection does not appear to add value in absence of clinic suspicion for malignancy.

Surgical management of carotid body tumor - Is Shamblin classification sufficient to predict surgical outcome?

Background The study aims to conduct a review of the surgical management of carotid body tumor. Methods Consecutive patients with CBT who received surgical interventions from January 1994 to January 2014 at our institution were reviewed. Clinical, operative, pathological and follow up information were reported. Results Twenty patients (four males; median age was 36) with 21 CBT operations were recorded during the period. One patient undertook sequential operations for bilateral CBTs. Patients had 19 neck mass, 1 incidental finding and 1 facial nerve palsy. Six CBTs (28.6%) were Shamblin class I, ten (47.6%) were class II and five (23.8%) were class III. Nine CBTs had preoperative conjunctive embolization. Two operations required internal carotid artery resection and reconstruction. Four patients received subtotal resections, while 17 achieved complete resection. Complications included two major strokes, three hoarse voice and two Horner's syndrome. Shamblin class was significant predictor of operative time, blood loss, and whether complete resection accomplished, but could not predict postoperative complication. With median follow up period of 94 months, there was no tumor recurrence found in those had complete resection. Conclusions This small cohort showed that Shamblin class was significant in predicting technical difficulties but could not predict occurrence of complications.

Color Doppler Ultrasound in Diagnosis and Assessment of Carotid Body Tumors: Comparison with Computed Tomography Angiography

A carotid body tumor (CBT) is a rare, non-chromaffin paraganglioma, and its diagnosis mainly depends on imaging modalities. The aim of this study was to investigate the ability of color Doppler ultrasound (CDU) in the diagnosis and assessment of CBT based on computed tomography (CT). We retrospectively reviewed the CDU and CT features of 49 consecutive CBTs and 23 schwannomas from 67 patients and compared these findings with surgical resection specimens. The mean size of CBT lesions on ultrasound scans and CT angiography (CTA) was 3.24 cm ± 0.82 cm (range, 1.6–5.2 cm) and 3.84 cm ± 1.08 cm (range, 1.8–6.8 cm), respectively, which had statistically significant difference (t = 9.815, p = 0.000). The vascularity of CBT lesions was richer than that of schwannoma lesions (p < 0.05). Intra-lesional vascularities feeding CBT mostly arose from the external carotid artery and had spectrum characteristics including low velocity and resistance. Peak systolic velocity (PSV) and resistance index (RI) of the vasa vasorum were 39.8 cm/s ± 19.8 cm/s and 0.54 ± 0.06, respectively. There was the correlation between CTA and CDU in identifying Shamblin type I CBT lesions, while CTA technique was superior for CDU, identifying Shamblin type II and III CBT lesions. Accuracy, specificity and sensitivity of CDU in diagnosing CBTs were 87.5% (63 of 72), 82.6% (19 of 23) and 89.8% (44 of 49), respectively. Both accuracy and sensitivity of CTA in diagnosing CBTs were 100%. CDU can be useful for assessment of Shamblin's type and intra-lesional blood flow of CBTs before its metastases, while CT imaging can reveal the relationship between lesions and adjacent arteries, as well as the involvement of the skull base. CDU combined with CT imaging can be used as an optimal detection modality for the assessment and management of CBT.

Surgical Management of Carotid Body Tumors: A 15-Year Single Institution Experience Employing an Interdisciplinary Approach

Cervical paragangliomas are rare neoplasms that arise from extraadrenal paraganglia in close association with the cranial nerves and extracranial arterial system of the head and neck, and therefore surgical extirpation can be challenging. A retrospective study was conducted of all patients undergoing surgical excision of a cervical paraganglioma between 2000 and 2015. The demographic characteristics, clinical features, surgical approach, and outcomes were reviewed. A total of 20 cervical paragangliomas were excised in 17 patients. There were 14 female and 3 male patients with a mean age of 56.6 ± 17.0 at the time of operation. Twelve patients had unilateral tumors and 5 patients had bilateral tumors. Familial involvement was confirmed by history or direct genetic analysis in 8 (47%) of the 17 patients. There were no malignant paragangliomas, and only 3 patients had tumors that were determined to be functional. Tumor size ranged from 1.3 to 6.0 cm. Two patients required combined arterial resection as part of complete excision of the tumor. There were no permanent operative cranial nerve injuries, no recurrences, minimal morbidity, and no mortality. In conclusion, optimal management of cervical paragangliomas should include a thorough preoperative evaluation, accurate definition of the surgical anatomy, and exclusion of synchronous paragangliomas. A combined therapeutic approach by a multidisciplinary team including surgeons and interventional radiologists provides safe and effective management of cervical paragangliomas with very low morbidity and excellent outcomes.

Current Surgical Management of Carotid Body Tumors

Carotid body tumors (CBT) are rare, and vascular surgeons are frequently involved in their care. Current guidelines for management are varied and may include genetic testing consisting of identification of succinate dehydrogenase (SDH) gene mutations. We performed a review of the surgical management of CBT at our institution to evaluate current outcomes and genetic testing impact. A retrospective analysis of all surgically treated CBTs at our institution was performed on all patients who underwent surgical excision of a CBT from 1996 to 2015. Data were obtained regarding preoperative demographics, intraoperative details, postoperative morbidity, and long-term outcomes. A total of 199 CBT were excised from 183 patients (122 female [66.6%]). A total of 113 patients (56.8%) presented with a neck mass, and 44 patients (22.1%) presented with tenderness or neck pain. Four patients (2%) had dysphagia on presentation, and three patients (1.5%) had cranial nerve dysfunction, CT (118 patients [59.3%]) or MRI (104 patients [52.2%]) were the most commonly used imaging modalities. Ultrasound was used in the diagnosis of 55 (27.6%) tumors. A total of 81 patients (40.7%) underwent preoperative angiography, and 68 of these patients (83.9%) underwent angiographic intervention consisting of embolization and/or internal carotid artery balloon occlusion testing. Mean tumor diameter on preoperative imaging was 3.15 cm (range, 0.4-7.2 cm). There were 81 (40.7%), 77 (38.7%), and 41 (20.6%) Shamblin type 1, 2, and 3 tumors, respectively. Average operating time was 222 minutes (range, 52-696 minutes). Average operative blood loss was 138 mL (range, 10-2000 mL). A total of 30 patients (15.1%) underwent arterial ligation, most commonly the external carotid artery. Arterial reconstruction with an interposition graft was required in 11 patients (5.5%), which consisted of saphenous vein (n = 7) or Dacron (n = 4). Patch angioplasty was performed in 4 cases (2%) with bovine pericardium used in 3 (1.5%) and Dacron used in 1 (0.5%). A total of 110 patients (55%) underwent concurrent lymph node excision (415 total nodes excised), and all were found to be benign. There were no deaths ≤30 days. A total of 37 patients (20.2%) had a family history of carotid body tumors. A total of 18 of 19 patients (9%) had genetic testing positive for a SDH mutation. Positive genetic testing for SDH mutations had a statistically significant correlation with positive family history of CBT (P < .0001), earlier age of presentation (P < .0001), symptomatic presentation of CBT (P < .0001), and postoperative complications after CBT excision (P < .0001). Mean age at diagnosis of patients with SDH mutations was 38.8 years, whereas patients without SDH mutations presented at a mean age of 51.3 years. In patients with SDH mutations, mean tumor diameter, average operating time, average operative blood loss, and distribution of Shamblin type 1, 2, and 3 lesions were not significantly different from patients without SDH mutations. Carotid body tumors can be treated with minimal morbidity and mortality; however, the subgroup of patients with positive SDH mutations may represent a variant group of younger patients with greater postoperative morbidity. Vascular surgeons should be aware of genetic testing to identify patients who may be at greater risk of operative morbidity. Concomitant lymph node excision does not appear to add value in the absence of clinic suspicion for malignancy.

Multidisciplinary Management of Carotid Body Tumors in a Tertiary Urban Institution.

Objective. Aim of this study is to present the experience of our institution in carotid body tumors (CBTs) treatment. Methods. All cases treated in a Vascular Surgery Department within 2.5 years (03/2013–09/2015) were retrospectively evaluated. Demographics, diagnostic, and treatment strategy were recorded. All patients with known CBT underwent ultrasound and magnetic resonance imaging preoperatively. All cases were classified according to the Shamblin type and evaluated by a radiologist, otolaryngologist, and anesthesiologist before and after surgery. Major outcomes included mortality, stroke, cranial nerve injury, and recurrence. Results. Overall, nine patients (mean age: 59.5 ± 16.3 years) with a total of ten CBTs were treated. There was no gender prevalence and most of the cases (55%) were asymptomatic. There were no functional or familial cases. There was only one bilateral case treated in a staged manner. No preoperative embolization of CBTs was performed. Mortality and stroke rates were null. No severe complication was observed in the early and late setting. No malignancy was recorded. Mean follow-up was 15.6 ± 7.8 months. Conclusions. Multidisciplinary management of patients with CBTs is imperative for optimal results, especially in type III tumors, bilateral or functional cases. After careful treatment planning and intraoperative manipulations, complications could be avoided even without preoperative embolization.

A 10-year Experience on Surgical Management of Carotid Body Tumors

Background: Carotid body is a highly-specialized organ located at the bifurcation of the common carotid artery and responsible for acute adaptation to hypoxia. The most common disease state of carotid body is its enlargement. Carotid body tumors (CBTs) are infrequent and slow growing tumors that must be considered in lateral neck mass evaluations. Objectives: In this study we aimed to review the clinical characteristics and management of CBTs in Shohadaye Tajrish Center during the last ten years (2002 - 2012). Materials and Methods: This was a retrospective study in which the medical records of patients diagnosed with CBT during the past ten years (from April 1st 2002 to April 1st 2012) were reviewed. The hospital ethics committee approved the extraction of data. For data collection we used a structured questionnaire, designed in six categories: demographic data, life style and predisposing factors, symptoms upon presentation, imaging results, treatment, complications, and follow up. Selected junior residents were responsible for extracting the data from the medical records and fulfilling the forms. Results: Overall, 48 patients with 51 CBTs were included in the study. The CBTs were bilateral in 3 (6.25%) cases. The cardinal presentations of these cervical masses were unanimous in all patients; 6 (12.5%) had symptoms of cranial nerve palsy. All cases had surgeries, while 3 patients with UN resectable tumors regarding massive invasion to CCA, ICA, and ECA, were treated with radiation simultaneously. The follow-up period in surgically resected CBTs did not elucidate any cause for the recurrencies. Conclusions: This study provided clinico-epidemiological data on patients with CBT, which could be useful for prompt diagnosis and appropriate work-up for patients and families with CBTs.

Management of Carotid Body Tumors: A Report of First 8 Cases

Management of Carotid Body Tumors: A Report of First 8 Cases

Management of Carotid Body Tumors: A Report of First 8 Cases

Management of Carotid Body Tumors: A Report of First 8 Cases

Diagnosis and management of carotid body tumor: a report of seven cases

Paragangliomas are rare asymptomatic painless tumors, originating from paraganglionic bodies of autonomous nerve system of the embriological neural crest and increasing gradually. Despite their gradual developing nature, it is critical to reach early diagnosis and tailor surgical plan for carotid body tumors due to their potential of being malignant and local aggressive development, as well as invasion or pressure on the adjacent vascular and neural tissues. In this article, we present seven cases who were admitted with the complaints of pain and swelling in the neck and were diagnosed with carotid body tumor based on the further investigations and were surgically treated in the light of literature review and different surgical modalities were discussed.

Perioperative Approach in the Surgical Management of Carotid Body Tumors

Now, surgical resection still remains the gold standard for the treatment of carotid body tumors (CBTs). Although advances in surgical techniques and the introduction of sensitive imaging modalities have significantly reduced mortality, the incidence of perioperative neurovascular complications, especially cranial nerve deficit and intraoperative hemorrhage, remains considerable. To solve these problems, preoperative embolization has been suggested; the reported benefits of preoperative embolization performed <48 hours before surgery include a reduction in tumor size, decreased blood loss, and improved visualization, theoretically reducing neurologic morbidity by lessening the risk of stroke and damage to cranial nerves. The purpose of this study was to review our experience in the surgical management of CBTs with preoperative embolization and evaluate the outcomes and complications according to the Shamblin classification. Thirty-two patients who had been diagnosed with and surgically treated for CBTs were enrolled from January 2005 till July 2010. All perioperative scans were evaluated by computed tomography angiography. We reviewed patient demographics, radiographic findings, and surgical outcomes collected from medical records. Thirty-two patients underwent surgical excision without mortality. Angiography with selective preoperative tumor embolization was performed on 21 patients. The median blood loss, operation time, and hospital stay for these patients were significantly reduced compared with those without embolization. There were no recurrences or delayed complications at the median follow-up of 20 months. Embolization as an adjunctive tool was beneficial for CBT surgery outcomes. Embolization should only be undertaken in those vessels that can be subselectively catheterized and determined not to allow free reflux of contrast medium into the internal carotid artery. Tumor embolization was performed on patients with Cook detachable coils, which are highly effective for supply artery closure if properly selected, and complications can be minimized by proper selection and positioning of the coil. Operation within 48 hours after embolization is recommended to minimize revascularization edema or a local inflammatory response.

Impact of preoperative embolization on outcomes of carotid body tumor resections

This study assessed neurovascular complications in the surgical management of carotid body tumors (CBTs), with emphasis on those treated with and without preoperative embolization. We reviewed the clinical data of all consecutive patients with CBTs treated by surgical resection at our institution from 1985 to 2010. Outcomes were compared between Shamblin class II and III CBTs treated with preoperative embolization (EMB group) and with no preoperative embolization (NEMB group). A total of 131 patients (80 women, 51 men), who were aged 48 years (range, 16-84 years), had resection of 144 CBTs and 12 concurrent cervical paragangliomas. This included 18 patients who had bilateral resections and 29 with familial CBTs. Succinate dehydrogenase (SDHx) mutations were confirmed in 17 patients. Mean tumor volume was 20.5 cm(3) (range, 0.8-101.3 cm(3)), and there were two biochemically active CBTs (1%). There were 71 Shamblin II and 33 Shamblin III. The EMB group underwent 33 CBT resections, and the NEMB group underwent 71. There were more patients in the EMB group with bilateral (48% vs 22%; P = .01) and familial (34% vs 14%; P = .01) CBT; otherwise, patient demographics, Shamblin class, and tumor diameter and volumes were similar. No strokes or other major complications occurred after preoperative embolization with polyvinyl alcohol particles 1 day before surgery. The EMB group required less extensive procedures (simple excision in 97% vs 82%, P = .03; internal carotid artery clamping in 15% vs 37%, P = .04) and had less blood loss (mean estimated blood loss, 263 vs 599 mL; P = .002) than the NEMB group. However, there were no significant differences in operative time (250 vs 265 minutes; P = .49), temporary cranial nerve injury (52% vs 38%; P = .21), clinically apparent cranial nerve deficits after 1 year (12% vs 7%; P = .46), deaths (0% vs 0%; P > .99), stroke (0% vs 1%; P > .99), or postoperative length of stay (4.1 vs 4.2 days; P = .91). Large CBTs can be resected safely with or without preoperative embolization. Preoperative embolization may simplify the conduct of the operation and reduce blood loss but does not decrease rates of cranial nerve injury, although most are temporary.

Carotid body tumour - an experience of 8 years at SSKM Hospital, IPGME&amp; R, Kolkata, India

Objective To review our experience of management of carotid body tumours at SSKM hospital, IPGME&R, Kolkata, India.

Advances in assessment and management of carotid body tumors

Evolving technology has the potential to alter the overall management of carotid body tumors (CBTs). We review our 35-year experience emphasizing on novel modalities available in the evaluation and treatment of CBTs. Medical records of 27 CBT patients between 1975 and 2009 were retrospectively reviewed. The study cohort has been arbitrarily divided into two groups: the early years' group A (18 patients, 1975-1998) and the later years' group B (9 patients, 1999-2009). The most common presenting symptom was a painless lateral neck mass (89%). Octreotide scintigraphy and genetic testing were routinely used for group B. In two cases, octreotide scintigraphy was coupled with intraoperative radiolocalization of the lesion. Preoperative embolization was performed in four CBTs. Among group B patients, five were pretreated via a covered stent placement in the external carotid artery (ECA). Twenty-three patients (24 CBTs) were eventually operated upon. One cardiovascular death, one permanent vocal cord paralysis and six transient cranial nerve injuries account for a 4.4% 30-day mortality and a 30.4% morbidity with no significant differences among groups. In conclusion, appropriate use of new techniques in CBT management has improved diagnostic accuracy and early detection without clearly affecting overall outcome in our study cohort.

Surgical management of carotid body tumors: Govt. Medical College Jammu experience

Background A retrospective study of patients with carotid body tumors which is a rare clinical entity is being presented.

Preoperative Angiography and Transarterial Embolization in the Management of Carotid Body Tumor: A Single-Center, 10-year Experience

Conclusion: Preoperative embolization of carotid body tumors (CBTs) is safe and effective to facilitate surgical resection. Summary: Larger CBTs, classified as Shamblin class II (those that partially surround the internal and external carotid arteries) and Shamblin class III (those that completely surround the carotid bifurcation and/or the internal carotid artery) can be difficult to remove, and excessive blood loss is possible. Some surgeons therefore advocate preoperative embolization of larger, Shamblin class II and III CBTs. Others believe preoperative embolization is unnecessary and has the added risk of neurologic complication. The authors present a series of 62 patients with Shamblin class II or III tumors that were operated on during a 10-year period in their institution. They divided the patients into two groups. The first group (group I) had preoperative embolization and included 33 patients with 11 class II and 25 class III lesions. Group II had surgery without preoperative embolization and included 29 patients with 9 class II lesions, and 21 class III lesions. The two groups were compared with respect to mean intraoperative blood loss, operation time, postoperative hospital stay, and clinical complications. The authors felt that angiography after embolization demonstrated complete CBT devascularization in 76% of the lesions and partial devascularization in 24%. Mean intraoperative blood loss was 354 ± 334 mL in group I vs 656 ± 498 mL in group II (P = .008). The mean operation time was 170 ± 75 minutes in group I vs 224 ± 114 minutes in group II (P = .034). Hospital stay was prolonged in both groups, but was still less in group I (8.0 ± 2 days) than group II (9.5 ± 3.5 days; P = .042). Transient ischemic attacks occurred in 10.3% of patients in group II vs in 3% of patients in group I. Cranial nerve injuries occurred in 13.8% of patients in group II and were not observed in group I. Comment: This is the largest published series of CBTs operated on with preoperative embolization. Apparently, although not specifically mentioned, there were no significant complications associated with the preoperative embolization, and the procedure was successful most of the time. It is unclear how the patients were allocated to group I or group II, with allocation likely on the basis of surgeon preference. It is also unclear whether inclusion into group I or group II changed over time and whether the same proportion were operated by the same surgeons in group I and group II. Therefore, the benefits of preoperative embolization in terms of operative time and blood loss, although potentially ascribed to the procedure, may also be surgeon-specific. Nevertheless, it does appear that preoperative embolization of larger CBTs can be done with technical success and minimal complications.

Preoperative Angiography and Transarterial Embolization in the Management of Carotid Body Tumor: A Single-Center, 10-Year Experience

Preoperative Angiography and Transarterial Embolization in the Management of Carotid Body Tumor: A Single-Center, 10-Year Experience

Preoperative Angiography and Transarterial Embolization in the Management of Carotid Body Tumor: A Single-Center, 10-Year Experience

Sixty percent of paragangliomas are located unilaterally at the carotid bifurcation. These are referred to as carotid body tumors (CBTs). To present our 10-year experience in the management of patients with CBTs, and to evaluate the efficacy of angiography and preoperative embolization technique in this retrospective study. Sixty-two patients with surgically removed CBTs (Shamblin class II and III), were divided into two groups. Group I, the preoperative embolization group, included 33 patients with 11 class II lesions and 25 class III lesions. Group II, the group that had surgery only, without preoperative embolization, included 29 patients with 9 class II lesions and 21 class III lesions. Comparisons were made between the groups in terms of mean intraoperative blood loss, mean operation time, mean postoperative hospital stay, and clinical complications. In group I, post-embolization angiography demonstrated complete tumor devascularization in 25 (76%) lesions and partial devascularization in 11 (24%) lesions. All but 1 (2%) lesion were completely excised. Mean intraoperative blood loss, mean operation time, and mean hospital stay were 354.8 ± 334.4 mL, 170.3 ± 75.4 min, 8.0 ± 2.1 days in group I and 656.4 ± 497.4 mL, 224.6 ± 114.0 min, 9.5 ± 3.5 days in group II, respectively. In group II, 27 lesions (91%) were completely removed. The transient ischemic attack (TIA) and cranial nerve injury incidence rates were 10.3% and 13.8% in group II and only 3% for TIA in group I. These results suggest angiography is highly valuable for the diagnosis of CBT. Preoperative selective embolization of CBT is an effective and safe adjunct for surgical resection, especially for Shamblin class II and III tumors.

A rare case of familial carotid body tumor in a patient with bilateral fibromuscular dysplasia

Carotid body tumors (CBTs) are neuroendocrine tumors that arise due to mutations of respiratory cycle enzymes. Fibromuscular dysplasia (FMD) is a disease that causes narrowing of medium-sized arteries. There is no documented link between CBT and FMD. In this article, we report a case of a patient with bilateral carotid FMD and familial CBT, including one in an identical twin who underwent successful surgical excision of the CBT. We describe specific considerations in the management of CBT in patients with concomitant carotid FMD. Also, we review the literature about the genetics of familial CBT and its possible relationship to the etiology of FMD.