[ANAPLASTIC TRANSFORMATION OF METASTATIC PAPILLARY THYROID CARCINOMA IN A CERVICAL LYMPH NODE - A TIMELINE].

INTRODUCTION: Anaplastic thyroid cancer (ATC) is accepted as transformation of a pre-existing glandular papillary thyroid carcinoma (PTC). Anaplastic transformation within a neck PTC metastasis is extraordinary. We present a patient with an exceptional timeline of an untreated neck PTC recurrence and its rare anaplastic transformation. In 2010, a 68-year-old patient with PTC and neck metastasis, (Stage III/Stage II 7th/8th AJCC, respectively) underwent thyroidectomy and neck dissection followed with radioiodine treatment (150 mCi). In 2012, he received an additional 150 mCi following an iodine scan suggested right neck recurrence. In late 2013, ultrasound revealed a 2.3 cm, suspicious right neck lymph node (level II-III). Only in 2017, after growing to 2.7 cm, the patient consented to undergoing a fine needle aspiration. PTC was verified, yet intervention was declined. In June 2018, he presented with a rapid growing neck mass occupying right levels II,III, carotid artery encasement and jugular vein involvement. A large bore needle biopsy revealed a highly malignant tumor, surrounded by necrosis, positive for cytokeratin (CK MNF 116), thyroid lineage marker (PAX8), negative for TTF-1 and thyroglobulin, i.e., ATC. The patient passed away in November 2018. In comparison, a patient with an identical primary staging received equivalent primary treatment. Yet, among the PTC nodular metastasis found in the neck specimen, one had ATC transformation. Over a 12-year follow-up there was no recurrence. To conclude, untreated PTC neck recurrence may have long-term consequences, such as rare anaplastic transformation. Although a case study, it advocates treating PTC neck recurrence.

Reversible conductive hearing impediments among patients with severe brain injury.

Purpose: Rehabilitation of patients with severe traumatic brain injury may include auditory stimuli. Hampering the function of the external, middle ear or Eustachian tube generates a conductive auditory deficit up to 35 dB that may potentially hinder auditory rehabilitation. The objective was to evaluate the incidence of conductive hearing impediments among patients with severe brain injury.Methods: The cross-section study included adults with severe brain injury hospitalized in a rehabilitation center. The patients presented with a prolonged vegetative state, were dependent on mechanical ventilation and gastrostomy tube feeding. Assessment of external, middle ear and Eustachian tube included otoscopy, tympanometry, nasopharyngoscopy, gag reflex and soft palate evaluations.Results: Nineteen patients (38 ears) were evaluated: 14 males and 5 females, aged 18-93 years (average 59). All patients had a normal nasopharynx, lacked a gag reflex, palatal movements or supraglottic sensation. Eighteen ears (47%) had middle ear effusion, 26 (68%) ears had cerumen impaction, and 14 (37%) had both.Conclusions: Many patients with severe brain injury have reversible and treatable impairments that cause potential conductive hearing loss. Routine otoscopic examination and treatment if required, that is, removal of impacted cerumen or middle ear drainage, have rehabilitating and general health benefits.Implications for rehabilitationAuditory stimulation was suggested for rehabilitation in patients with severe traumatic brain injury.Many patients have cerumen and/or otitis media with effusion causing conductive hearing impairment as well as general health issues.Both aural impediments are diagnosed by routine otoscopy, are easily treated, and may affect rehabilitation.

Tinnitus Perspectives among Israeli Ear, Nose and Throat Physicians: A Nationwide Survey.

OBJECTIVES: To study the compliance of ear, nose, and throat (ENT) physicians to the American Association Otolaryngology-Head - Neck Surgery (AAO-HNS) clinical practice guidelines (CPG) for tinnitus and to identify the disparity of both diagnosis and management options in the absence of a local protocol for the management of adult tinnitus. MATERIALS AND METHODS: A voluntary and anonymous questionnaire was emailed in a Google spread-out sheet format to all practicing ENT physicians across the country (n=370). Overall, 126 ENT physicians responded to the questionnaire (34% of the physicians to whom the questionnaire was sent). RESULTS: Medical history focuses on tinnitus characteristics and otological signs, and symptoms are often queried (80%-98%). Physicians routinely perform an otoscopic examination, whereas other relevant possible physical findings, such as temporomandibular joint disorders or neck trauma, are less frequently examined. Treating physicians have the most frequent recourse to sound therapy and cognitive behavioral therapy in accordance with AAO-HNS CPG. CONCLUSION: The publication of the AAO-HNS CPG for tinnitus is important, permitting a common approach for the diagnosis and management of primary tinnitus (PT). A diagnosis and management scheme that takes into consideration both the AAO-HNS CPG for tinnitus as well as physician diagnosis and management paradigms is suggested.

Effect of general anesthesia and intubation on parathyroid levels in normal patients and those with hyperparathyroidism.

BACKGROUND: Induction of general anesthesia and endotracheal intubation may precipitate parathyroid hormone (PTH) elevation in patients with primary hyperparathyroidism (HPT). The purposes of this study were to revisit this observation and to study its impact in healthy patients. METHODS: Patients with primary HPT who underwent parathyroidectomy were retrospectively studied. The PTH was sampled and compared: before, immediately after general anesthesia and endotracheal intubation, and 15 minutes after parathyroidectomy. Healthy adults who underwent elective operations were prospectively studied. The PTH was sampled before general anesthesia and endotracheal intubation, immediately after, and 15 minutes later. RESULTS: Thirty-one patients, aged 28-89 years (mean 60.1 ± 13 years), were retrospectively studied. The PTH was significantly elevated after general anesthesia and endotracheal intubation (P = .014). Fifty patients, aged 21-86 years (mean 54 ± 15 years), were prospectively studied. The PTH elevation after general anesthesia and endotracheal intubation was not significant. CONCLUSION: General anesthesia and endotracheal intubation causes an immediate, steep, and significant PTH elevation in patients with primary HPT but only a minor change in healthy adults. The difference may be attributed to an impaired adrenergic response in patients with primary HPT.

The Middle Ear Cleft Status in a "Natural" Cohort With Eustachian Tube Dysfunction.

BACKGROUND: The Eustachian tube (ET) has a major role in the middle ear (ME) pressure homeostasis. ET dysfunction is the accepted paradigm for pressure-related ME disorders. We studied the ME status in patients with severely diminished ET opening abilities, and anticipated to find ME disorders in most of them. PATIENTS AND METHODS: ME status was evaluated in unconscious adults, who were hospitalized in a rehabilitation center with severe brain damage, requiring tracheotomy and gastrostomy. These patients were unable to swallow, produce valsalva, yawn, and needed oral suctioning. Examination included fiberoptic nasopharyngoscopy, gag reflex and soft palate assessments, otoscopy, and tympanometry. RESULTS: Nineteen patients (38 ears) were evaluated: 14 men and 5 women, aged 18 to 93 years (average 59). Duration of gastrostomy and tracheotomy were between 3 months and 18 years. All the patients lacked gag reflex, palatal movements, or supraglottic sensation. Eighteen ears (47%) had otitis media with effusion (OME) (versus ∼3% in the general population, p = 0.00001), none had significant tympanic membrane atelectasis, but 20 (53%) ears were normal. Twenty-two ears (59%) had tympanometry types B/C and 16 (41%) had type A. Cerumen impaction incidence (26 ears, 68%) was significantly higher than in normal adults (10%), mentally retarded (36%), and nursing homes residents (57%). CONCLUSIONS: A dysfunctional ET predisposed ME disorders. Yet, ∼50% of the ears were normal, in contrast to the current paradigm. This implies that ME pressure homeostasis is maintained by factors that can compensate for ET dysfunction. Treating cerumen impaction and OME may be beneficial for rehabilitation.

Cardiovascular Risk Factors Among Patients With Vestibular Neuritis.

OBJECTIVE: To investigate the correlation between cardiovascular risk factors (CVRFs) and vestibular neuritis (VN) in hospitalized adult patients. METHODS: A cross-sectional retrospective study was conducted in a tertiary hospital setting. The medical records of patients (aged over 18 years old) who were hospitalized between the years 2005 and 2014 with the diagnosis of VN were retrieved. Inclusion criteria were: (1) acute vertigo lasting for at least 24 hours, (2) absence of auditory complaints, (3) horizontal unidirectional nystagmus present during physical examination, and (4) absence of neurological symptoms or signs. The ratio of CVRFs among VN patients was compared to the ratio of those among the general Israeli population. RESULTS: A significantly higher prevalence of CVRFs was found among VN hospitalized patients in comparison to the general population ( P < .05). Furthermore, a significant correlation ( P < .001) was found between the patients' age and the number of CVRFs (r = .387). A positive correlation (r = .643) was found between the number of CVRFs and VN in each age group ( P = .119). CONCLUSION: There may be a possible interrelation between CVRFs and VN. This correlation can be caused by occlusion of small blood vessels leading to labyrinthine ischemia and apparition of symptoms of VN.

The Impact of Tobacco Smoking Upon Chronic/ Recurrent Tonsillitis and Post Tonsillectomy Bleeding

Abstract Introduction Smoking has many adverse effects on the oral and pharyngeal mucosa. Outcomes may be developing tonsillar infections and predisposing for post tonsillectomy bleeding (PTB). Objective The objective of our study was to determine whether smokers have more chronic/recurrent tonsillitis indicating for tonsillectomy or develop more PTB episodes. Methods We conducted a retrospective study on two groups of adults (age ≥18 years). Cohort 1: Smoking among patients who underwent tonsillectomy for recurrent/ chronic tonsillitis. Cohort 2: Smoking among patients requiring control of PTB that were operated primarily for recurrent/chronic tonsillitis. Cohort 1 served as a populationreference for the second. We retrieved the data from medical records. Results Cohort 1: 206 adults aged 18-50 years (mean 26 ± 7.6). 28% (57 patients) were smokers, versus 24% and 20% in the general population (in the years 2000 and 2010; p = 0.5, p = 0.18, respectively). Cohort 2: 114 adults aged 18-73 years (mean 26 ± 7.6). 43% were smokers, double the incidence in the general population (p = 0.004, p = 0.0004, in 2000 and 2010, respectively), and 1.5 times cohort 1 (p = 0.02). Smoking rates among bleeders on post-operative days 8-10 and later than day 10 were 53% and 60% (p = 0.0005 and p < 0.0001, respectively). Five of ten patients presenting a second PTB were smokers. Timing of re-bleedings was similar to their first PTB and dated similarly as first PTB of the entire group, mean 5.6 days (SD ± 3.2). Conclusion Smokers may encounter more chronic/recurrent tonsillitis episodes, indicating tonsillectomy and significantly are more prone for PTB. Smoking cessation may perhaps diminish recurrent/chronic tonsillitis.Whether pre-operative abstinence or its length would reduce PTB incidence is yet to be determined.

The Impact of Tobacco Smoking Upon Chronic/Recurrent Tonsillitis and Post Tonsillectomy Bleeding.

Introduction Smoking has many adverse effects on the oral and pharyngeal mucosa. Outcomes may be developing tonsillar infections and predisposing for post tonsillectomy bleeding (PTB). Objective The objective of our study was to determine whether smokers have more chronic/recurrent tonsillitis indicating for tonsillectomy or develop more PTB episodes. Methods We conducted a retrospective study on two groups of adults (age ≥18 years). Cohort 1: Smoking among patients who underwent tonsillectomy for recurrent/chronic tonsillitis. Cohort 2: Smoking among patients requiring control of PTB that were operated primarily for recurrent/chronic tonsillitis. Cohort 1 served as a population-reference for the second. We retrieved the data from medical records. Results Cohort 1: 206 adults aged 18-50 years (mean 26 ± 7.6). 28% (57 patients) were smokers, versus 24% and 20% in the general population (in the years 2000 and 2010; p = 0.5, p = 0.18, respectively). Cohort 2: 114 adults aged 18-73 years (mean 26 ± 7.6). 43% were smokers, double the incidence in the general population (p = 0.004, p = 0.0004, in 2000 and 2010, respectively), and 1.5 times cohort 1 (p = 0.02). Smoking rates among bleeders on post-operative days 8-10 and later than day 10 were 53% and 60% (p = 0.0005 and p < 0.0001, respectively). Five of ten patients presenting a second PTB were smokers. Timing of re-bleedings was similar to their first PTB and dated similarly as first PTB of the entire group, mean 5.6 days (SD ± 3.2). Conclusion Smokers may encounter more chronic/recurrent tonsillitis episodes, indicating tonsillectomy and significantly are more prone for PTB. Smoking cessation may perhaps diminish recurrent/chronic tonsillitis. Whether pre-operative abstinence or its length would reduce PTB incidence is yet to be determined.

The effect of immunization with pneumococcal conjugated vaccines on Streptococcus pneumoniae resistance patterns in acute otitis media.

Following the introduction of 7- and 13-pneumococcal conjugate vaccines (PCVs) in Israel, we demonstrated that within Streptococcus pneumoniae (Sp) positive middle ear cultures, obtained from young children with severe acute otitis media (AOM) episodes, there were more penicillin-susceptible and less multi-drug resistant Sp isolates in PCV immunized children.

Laryngeal Side Effects of Tyrosine Kinase Inhibitors.

OBJECTIVES: Tyrosine kinase inhibitors (TKIs) are common targeted drugs, used in the treatment of hematological and solid malignancies. These drugs present a multitude of potential adverse effects. Laryngeal manifestations, including laryngeal edema, secondary to TKIs treatment have not been well studied, despite their potential lethality. METHODS: This cross-sectional study included adult patients (>18 years) treated with TKIs who were followed in a secondary medical center and underwent a voluntary otolaryngological examination, which included laryngeal fiber-optic laryngoscopy (FOL). FOL was independently performed by two senior otolaryngologists, and results were recorded and evaluated by two grading systems, to assess the degree of laryngeal edema. In addition, medical files were reviewed, and data collected included past medical history, signs and symptoms, physical examination, laboratory results, treatment type, and duration. RESULTS: Sixteen patients, aged 68.2 ± 13.6 years, were examined during October 2014 to December 2014. Of them, three (19%) were males. Eleven (68%) patients presented with varying degrees of laryngeal edema. A significant correlation was found between gastroesophageal reflux symptoms and laryngeal edema (P = 0.02). TKI treatment was stopped in one patient, because of symptomatic laryngeal edema, which completely resolved within 2 weeks. CONCLUSIONS: Laryngeal edema was common in our study group. This edema was most often not life threatening. Yet, because of the potential severity of this side effect, we propose a routine FOL examination of patients before commencing TKI treatment and a reevaluation performed during treatment.

Is primary hyperparathyroidism a risk factor for papillary thyroid cancer? An exemplar study and literature review.

Introduction Primary hyperparathyroidism (PHPT) is associated with several cancer types, including papillary thyroid carcinoma (PTC). Objective To explore further the relation between PHPT and PTC. Methods By considering patients with PHPT as extra-suspicious for PTC, we studied an exemplar group of patients with PHPT with a small (≤1 cm) thyroid nodule, which was negative in preoperative cytologic examination. During parathyroidectomy, a frozen section biopsy of the thyroid nodule confirmed PTC, as did the final surgical specimen, revealing that the preoperative cytology was false-negative. Additionally, relevant reports retrieved from the English literature addressing thyroid cancer and hyperparathyroidism were reviewed and processed. Results Four patients with PHPT were studied. Three had a multifocal thyroid disease, and three had neck lymph node metastasis. Processing previous report data supported an association between PHPT and PTC. Although thyroid nodularity among patients with PHPT was similar to the general population, PTC incidence was higher. This was true also for patients with secondary hyperparathyroidism. Conclusions This study emphasized that PHPT should be considered as a noteworthy risk factor for PTC. Fine needle aspiration of a thyroid nodule is the most valuable diagnostic procedure for thyroid cancer. Yet, false-negative results were reported in up to 10% of cases, especially in small, subcentimeter nodules. In line with our data and the literature, patients with PHPT should have both a detailed ultrasound addressing the thyroid and cytology of any thyroid nodule, including small subcentimeter lesions. Moreover, surgical flexibility, allowing intraoperative thyroid nodule sampling, should be considered even for "innocent" nodules.

Is Primary Hyperparathyroidism a Risk Factor for Papillary Thyroid Cancer? An Exemplar Study and Literature Review

Introduction Primary hyperparathyroidism (PHPT) is associated with several cancer types, including papillary thyroid carcinoma (PTC). Objective To explore further the relation between PHPT and PTC. Methods By considering patients with PHPT as extra-suspicious for PTC, we studied an exemplar group of patients with PHPT with a small (1 cm) thyroid nodule, which was negative in preoperative cytologic examination. During parathyroidectomy, a frozen section biopsy of the thyroid nodule confirmed PTC, as did the final surgical specimen, revealing that the preoperative cytology was false-negative. Additionally, relevant reports retrieved from the English literature addressing thyroid cancer and hyperparathyroidism were reviewed and processed. Results Four patients with PHPT were studied. Three had a multifocal thyroid disease, and three had neck lymph node metastasis. Processing previous report data supported an association between PHPT and PTC. Although thyroid nodularity among patients with PHPTwas similar to the general population, PTC incidence was higher. This was true also for patients with secondary hyperparathyroidism. Conclusions This study emphasized that PHPT should be considered as a noteworthy risk factor for PTC. Fine needle aspiration of a thyroid nodule is the most valuable diagnostic procedure for thyroid cancer. Yet, false-negative results were reported in up to 10% of cases, especially in small, subcentimeter nodules. In line with our data and the literature, patients with PHPT should have both a detailed ultrasound addressing the thyroid and cytology of any thyroid nodule, including small subcentimeter lesions. Moreover, surgical flexibility, allowing intraoperative thyroid nodule sampling, should be considered even for "innocent" nodules. .

Otolaryngological aspects of sudden infant death syndrome.

INTRODUCTION: Sudden infant death syndrome (SIDS) is characterized by the sudden death of an apparently otherwise healthy infant, typically during sleep, and with no obvious case after a thorough post-mortem and scene death examination. OBJECTIVE: To address the problem from the otolaryngologist's perspective, describe relevant pathologies, discuss controversies and suggest preventive measures in high-risk populations. METHODOLOGY: A MEDLINE search and hand search were conducted to identify reports published between 1969 and 2011 in the English language on the pathophysiology of SIDS related to the head and neck organs. Search terms included SIDS (MeSH term), SIDS and pathophysiology (text words), and SIDS and autopsy (text words). DISCUSSION: A growing number of reports suggested head and neck organs involvement in SIDS autopsies. Laryngeal, oropharyngeal, maxillofacial, otologic, cervical vascular abnormalities and infectious etiologies, were recognized and discussed. CONCLUSIONS: Otolaryngologists should be aware of relevant pathologies, as some are treatable, if identified early enough in infancy. A proactive risk-management approach is warranted in infants presenting with certain abnormalities reviewed here.

Head and neck manifestations of 22q11.2 deletion syndromes.

The allelic loss of 22q11.2 results in various developmental failures of pharyngeal pouch derivatives ("22q11.2 deletion syndromes", 22q.11DS), consequently affecting the anatomy and physiology of head and neck (H&N) organs. The objective of this paper was to describe those manifestations. Two 22q11.2DS patients with H&N manifestations were studied along with a comprehensive review of the English literature, from 1975 to 2010 regarding the associated H&N malformations among 22q11.2DS. A 24-year-old mentally disabled 22q11.2DS male presented with right hemithyroid enlargement, causing significant compressive signs. Sonography revealed a homogeneous 8 × 3 cm lesion, replacing almost the entire thyroid lobe. Fine needle aspiration revealed colloid material and abundant eosinophils. The hemithyroidectomy specimen confirmed follicular adenoma. A 19-year-old mentally disabled 22q11.2DS female underwent CT-angiography due to an upper GI bleeding. The study revealed a vascular malformation in the infratemporal fossa. Reviewing the reported data regarding 22q11.2DS-associated H&N malformations revealed abnormalities and malfunctions of the thyroid gland, parathyroid glands, thymus agenesis, cleft palate, carotid artery aberrations, malformations of the larynx and trachea and esophageal dysmotility. 22q11.DS patients may present with H&N anatomical abnormalities, along with hormonal dysfunctions, which require special awareness once treatment is offered, especially when concerning anesthetic and surgical aspects. In addition, hSNF5/INI1, a tumor suppressor gene, detected at location 22q11.2 was described to be "knocked out" in some patients. This may be associated with H&N tumors reported in these patients.

Laryngocele: a rare long-term complication following neck surgery?

INTRODUCTION: Laryngocele is an abnormal dilatation of the laryngeal saccule. Suggested etiologies include congenital enlargement of the saccule, weakness of laryngeal tissues, and increased intralaryngeal pressure. Only a few reports have described the late evolution of laryngocele following neck surgery. CASE PRESENTATION: Two heavy smoking patients presented with hoarseness in voice because of laryngocele, which has evolved many years following ipsilateral neck surgery: hemithyroidectomy 20 years earlier and frontolateral hemilaringectomy 12 years earlier. Both patients were treated similarly by an endoscopic laser-assisted resection of the laryngocele. No other risk factor could have been attributed to its development. Follow-up was unremarkable. DISCUSSION: Laryngeal locus minoris violation may result in the development of laryngocele in the long run following neck surgery and may be considered as a late rare surgical complication. In addition, heavy smoking or its sequelae may predispose this condition.

Changing trends of peritonsillar abscess.

OBJECTIVE: This retrospective, cohort study aims to assess the changing characteristics of peritonsillar abscess (PTA). METHOD: Data were obtained from PTA patient records admitted to a secondary hospital over a 10-year period. RESULTS: A total of 427 patients, aged 31.6 +/- 15.2 years (range, 3-91), were treated for PTA, reflecting an incidence of 0.9/10 000/y. Forty-seven (11%) patients had more than one episode. There was no sex, seasonal, or side predominance. Thirteen (3%) patients developed complications. One hundred four (24.4%) patients were 40 years or older, had a longer hospital stay, and were prone to complications. One hundred two (23.8%) patients did not have an anteceding pharyngotonsillitis. Smoking was more common among patients with PTA as compared with the general population and was associated with more complications. A total of 283 (66.2%) patients developed PTA in spite of prior antibiotic therapy; 51.1% of smokers that received prior antibiotics had a higher incidence of Streptococcus viridans isolates. CONCLUSION: Peritonsillar abscess may have changed its characteristics: affecting more older patients having a worse and longer course and PTA evolvement without anteceding tonsillitis or in spite of a prior adequate antibiotic therapy. Smoking may be a predisposing factor.

The growth rate and size of the mastoid air cell system and mastoid bone: a review and reference.

This review suggests a reference to the postnatal growth of mastoid air cells and bone. Information was retrieved from studies having large consecutive age groups, in order to reveal a development pattern. Data regarding origin, gender, and antibiotic treatment was investigated as well. Most measurements were obtained by planimetry. Assessment of the various data sources suggested the antrum to be well developed at birth (1-1.5 cm2), the mastoid cells to be about 3.5-4 cm2 at 1 year, followed by a linear growth till the age of 6 (1-1.2 cm2/year), having a slower increment up to adult size at puberty (approximately 12 cm2). The mastoid bone expansion is about 0.6-0.9 cm/year in length and width and 0.4 cm/year in depth in the first year, followed by half that rate until the age of 6-7. At puberty there was a slower sprout reaching adult size. Different ethnic groups share similar mastoid aeration and bone growth patterns. There were no differences between mastoid aeration measured at the pre-antibiotic era and after its widespread use. In conclusion, there are three distinguishable phases of mastoid pneumatization from birth till reaching final size. Bone and air cell compartments share a similar growth pattern; bone expansion lags behind aeration. Antibiotic treatment for otitis may have no impact upon mastoid aeration.

Middle ear pressure change as a function of body position.

OBJECTIVE: To verify and assess immediate middle ear (ME) pressure changes as a function of body position. STUDY DESIGN: A prospective clinical trail. PATIENTS AND METHODS: Twenty-six adult volunteers having 52 normal, healthy ears had tympanometric ME pressures measured in an upright and recumbent positions. Recordings were obtained immediately after positioning and after 3 minutes. The main outcome measure was the pressure difference between upright and recumbent measurements, that is, positional ME pressure change. RESULTS: All ME pressure recordings were within (-)100 to (+)55 mmH(2)O. An instant and significant (P < .001) pressure elevation was recorded in all ears once position changed from upright to recumbent. The average pressure increment was 19 mmH(2)O. Once a recumbent ear was repositioned upright it demonstrated an immediate pressure drop and regaining the initial ME pressure. Assuming the volume of a normal ME cleft as 8 mL and following Boyle's law, an ME volume alteration of about 17 microL was required to induce such pressure change. CONCLUSIONS: Positional pressure changes were within the range of normal daily ME pressure variations. The instantaneous pressure changes and reversibility may be explained by filling and emptying of blood vessels within the ME cleft, following gravity causing an alteration of the aerated volume. Individual differences of pressure change may follow variability of ME cleft volume, its surface, and vessel density.