1990-12-18 Assigned to HEALTHSCAN PRODUCTS INC., A CORP. OF NJ reassignment HEALTHSCAN PRODUCTS INC., A CORP. OF NJ ASSIGNMENT OF ASSIGNORS INTEREST. Assignors: DANOWKI, THOMAS J., LARSON, DOUGLAS A.
An apparatus for dispensing a measured amount of a spray-entrapped product, typically dispensed by a metered dose inhaler device, includes an elongated passageway having a mouthpiece portion and a main chamber portion. The metered dose inhaler is mounted between the mouthpiece and main chamber portions such that upon operation its spray is directed away from the mouthpiece. A two-position valve is provided to allow a first, low-level flow to be developed through the unit, followed by a higher flow rate as the metered dose inhaler unit is operated. This increased flow, passing through the device in the direction opposite to that of the MDI spray, contacts the spray plume to cause a high level of mixing and a decrease in spray particle size which results in an efficient draw of the spray medication into the lungs of the user.
Many ailments and conditions of the human body require the administration of medication into the lungs of the patient. Typically, medication is provided by way of a metered dose inhalation (MDI) apparatus, comprising a pressurized container of the medication with appropriate valving to dispense a fixed amount of medication upon activation of the valve unit. The medication is inhaled to deliver the dispensed dose to the lungs.
While the amount of medication released per MDI cycle is accurately metered, the amount of medication actually reaching the lungs is far from consistent. To direct the medication to the lungs, the user must create an inspiratory flow of air, and must further time the flow to capture and engage the flow of medication, normally in the form of a mist, as it is released by the MDI. In addition, the high velocity of the emitted spray often results in a large portion of the drug being deposited in the mouth and oropharyngeal area, causing an unpleasant aftertaste, drug loss, and on occasion candidiasis.
To assist the user, a variety of devices have been developed to channel the MDI output. These devices, called "spacers", typically create a residence volume to accept the atomized spray until a breath is taken. Often, however, these devices introduce additional problems and complications, including awkwardness of use and the creation of complicated mechanisms which can defeat the inherent simplicity of the MDI system. The devices also often fail to gain user acceptance, as they are not small enough to provide the chronic respiratory disease patient with the ability to use the unit inconspicuously.
The present invention provides a MDI spacer unit which couples the actuation of the unit with inhalation. The medication spray is directed away from the mouth and teeth, and contacts and mixes with an oppositely directed flow of inspiratory air. As a result of this mixing, the length of the medication plume is reduced, allowing the patient to inhale the plume in a full breath. Accordingly, the proper dose of medication can be effectively administered within a unit that has a relatively small resident volume. This allows a compact unit to be produced.
Reversal of the medication spray causes the spray droplets to be diffused and evaporated. Remaining large drops will have the tendency to settle into the spacer chamber, rather than being drawn into the mouth of the user and being deposited on the mouth and teeth. Thus, a greater volume of medication capable of reaching the lungs is delivered to the user.
These and other benefits are achieved in the present invention by providing an elongated chamber divided into a mouthpiece section and a main chamber section. A transverse aperture adapted to accept the valve-bearing end of a metered dose inhalation dispenser unit is provided between the mouthpiece and main chamber portion. Nozzle means direct the MDI spray into the main chamber in a direction away from the mouthpiece when the metered dose inhalation dispenser is operated.
The open end of the main chamber portion of the unit is provided with first and second air-inlet aperture means, the first aperture being continuously open while the second aperture means has cover means coupled to the MDI dispenser whereby upon operation of the dispenser to release a dose of the medication, the cover means is displaced from a first position closing the aperture means to a second position whereby the aperture means are opened.
In operation, the patient inspires through the mouthpiece of the unit, the first aperture means allowing only a relatively small flow of air through the unit and into the mouth and lungs. Upon operation of the MDI dispenser, causing a metered dose of medication to enter the main chamber, the cover means is simultaneously opened, allowing a relatively large volume inrush of air to travel through the chamber in the direction opposite to that of the medication, as a result of the suction applied by the user. This rush impinges upon the MDI medication plume, reversing the plume's direction, and carrying it into the lungs of the user. Releasing the MDI dispenser to return to its normal closed position closes the cover means, resealing the second aperture means and resetting the apparatus for a subsequent dispensation. During periods of non-use, the MDI dispenser may be stored within the main chamber, providing a compact unit.
FIG. 7 is a side elevation view, in section, taken along line 7--7 of FIG. 6 showing the positioning of the dispenser within the spacer body.
Referring to FIGS. 1 and 2, spacer unit 10 comprises an elongated, generally tubular member 12 forming a mouthpiece section 14 and a main chamber portion 16, connected by an intermediate portion 18 which supports metered dose inhaler dispenser 20.
As known in the art, the MDI dispenser 20 includes a nozzle 22 projecting from an end of the unit. Depression of the nozzle with respect to the body of the MDI unit causes a measured and metered dose of the contained medication to exit, in the form of a spray, through the nozzle. To accommodate the dispenser 20, the intermediate portion 18 of the spacer unit is provided with a circular bore in the chamber wall surrounded by peripheral upstanding lip 24. The lip 24 may be of varying height about its circumference, due to the difference in diameter between main chamber portion 16 and mouthpiece portion 14. In a preferred embodiment, the inner diameter of the main chamber portion may be on the order of 1.2 inches with the mouthpiece inner diameter being approximately 0.74 inches, with a small outward flare along its length.
An internal pedestal 26, located directly below the MDI-accepting aperture, extends upwardly within intermediate portion 18, and is provided with a right angle bore 28, the vertical portion of which is dimensioned to accept and support the MDI nozzle 22. The lower end of the vertical portion may include a seat portion beveled at a 45 degree angle to accept various diameter MDI valve stems. The horizontal portion of the bore terminates in a flared portion 30, causing the MDI medication to be sprayed into the main chamber portion 16 in a direction away from the mouthpiece 14. It is to be appreciated that downward pressure applied to the MDI dispenser with the spacer unit 10 held rigidly will depress the nozzle 22 with respect to the dispenser, activating the dispenser spray.
Positioned within the main chamber portion 16 is tubular slide element 32, whose exterior diameter is chosen to interfit with the internal diameter of the main chamber portion. Slide unit 32 is of elongated configuration, having a lipped first end 34 which serves as a stop against the distal end 36 of main chamber portion 16, and an integral nozzle 38 at its second end.
In particular, nozzle portion 38 comprises a reduced diameter central passageway portion 40, whose center line is aligned with the horizontal portion of right angle bore 28, and which is joined to proximal end 42 of slide unit 32 by intermediate angular transition portion 44, which creates a tapered entrance into passageway 40. The angular transition portion 44 includes inwardly-angled wall 46, against which the lower edge 48 of the MDI dispenser rests. The angle between the wall 46 and the horizontally-extending portion of the slide is preferably about 135 degrees. With the slide fully inserted into main chamber portion 16, wall 46 just clears lower edge 48 with the MDI nozzle fully inserted into the bore 28. The passageway 40 maintains the velocity of the inspiratory air flow to insure reversal of the spray plume from the dispenser 20 before it transverses the full length of the slide element. The passageway diameter is preferably 0.50 inches.
The distal, lipped end 34 of slide unit 32 is covered by a cap or cover 50 of generally circular configuration having a peripheral lip 52 which overlies the lipped end portion 34. A bore 54 extends centrally through the cover, and may preferably be surrounded by a collar 56. The bore provides a first air-inlet aperture means into the slide unit and main chamber portion 16. An elastic band 58 may be affixed about the reduced diameter neck 60 of the collar, the ends of the band being attached to approximately-dimensioned projections 62 on the exterior of main chamber portion 16 to removably retain the cover against the end of the slide unit. The band, installed in a tensioned state, further biases the slide and cover into the position depicted in FIG. 2, providing a restoring force against rightward motion of the slide, which occurs due to the force exerted against angled wall 46 by the edge 48 of the dispenser 20 as the dispenser is depressed.
A series of apertures 64 are located and spaced about the periphery of the slide unit 32 proximate the capped end thereof, and are so positioned to be normally overlaid and covered by the distal end of main chamber portion 36, but exposed as the slide unit moves rightwardly with respect to the main chamber portion. These apertures provide a second air-inlet aperture means into the slide and main chamber portion 16 and, in conjunction with the first air inlet aperture means 54, form a variable sized air inlet means for the main chamber. In a preferred form, the apertures 64 are 4 in number and are in the form of 0.031 by 0.222 inch slots. The aperture 54 in cap 50 is 0.062 inch in diameter.
Operation of the unit is as follows: With the MDI dispenser in place, the user embraces the mouthpiece 14 with his or her lips 66, and inhales through the unit. In the start position of FIG. 2, the apertures 64 on the slide 32 are overlaid by the distal end of the main chamber 16, and accordingly a relatively low volume airflow is developed through the unit by ambient air entering the chamber solely through cap bore 54. A flapper or other form of noise generator 68 may be incorporated into collar 56 to provide an oral indication that a proper airflow rate has been developed.
When the airflow is developed, and as the user continues to inhale, the MDI dispenser 20 is depressed, as depicted in FIGS. 3 through 5. As shown therein, depression by the user's hand 70 upon the upper portion of the dispenser against the properly supported spacer unit 10 drives the dispenser body downward through the aperture formed by wall 24 with respect to the nozzle 22, causing the internal valve of the MDI dispenser to open and dispensing the medication spray through the nozzle. The spray is directed into main chamber portion 16 by the directional bore 28.
The downward pressure upon the MDI dispenser also causes its lower edge 48 to further bear against the angled wall 46, driving it and slide unit 32 rightwardly, overcoming the retaining force of the elastic band 58. This relative travel with respect to the main chamber portion 16 positions the second apertures 64 beyond the distal end of the main chamber portion, exposing them to the ambient air and allowing an increased flow of air to enter the main chamber to be drawn into the mouth and lungs of the user. In a preferred embodiment, the apertures 64 are opened prior to the time the medication is released. This relationship may be adjusted by varying the cam action relationship between the angled wall 46 and the lower edge of the MDI dispenser.
As a low-level airflow was previously created through the cap bore 54, the opening of the additional apertures 64 causes a higher flow rate of air to enter and travel through the unit, into which the simultaneously-emitted medication plume is released. This draws the medication back through the unit and into the mouth and lungs of the user. The meeting of the counter-directed flows improves dispersion by mixing the spray with to-be inspired ambient air, reduces the size of the spray droplets by increasing evaporation of the liquid in the droplets and assists in the removal of remaining large droplets from the stream such that the airflow entering the mouth will not deposit the carried medication on the mouth surfaces, but rather allows the medication to reach the lungs of the user. The size of apertures 64 maintains the flow rate of inspiration to approximately 30 liters/minutes at inspiratory vacuum pressure of 10 cm of water. In order to double the flow rate, the inspiratory vacuum would have to be quadrupled.
Because of the small internal volume of the spacer, all the suspended medication will be inhaled into the lungs within approximately 1/4 second after the spray from the MDI dispenser ceases. It is thus not necessary for the MDI dispenser to be held in the depressed position for the duration of the inspiratory breath, but only for the time period necessary to release the measured dose of medication. Release of the downward pressure on the MDI dispenser causes the slide unit to return to the left, rest position as shown in FIG. 2 by the restoring force of the elastic band 58. The angled wall 46 may further provide a secondary drive to raise the MDI dispenser. The second apertures 64 are closed, returning airflow through the unit to the initial, low volume state.
As may be appreciated in connection with consideration of FIGS. 6 and 7, the spacer unit of the present invention may further provide for a convenient storage mechanism for the MDI dispenser 20. In particular, the diameter of the main chamber 16 and slide 32 are such as to allow the dispenser 20 to be placed within the slide by removal of the cap 50 which exposes the open end of the slide. With the MDI dispenser placed within the chamber, the cap may be replaced and retained by the band 58, thus providing a secure location for the dispenser and further insuring that the dispenser and spacer remain together for subsequent use. The projections 62 on the exterior of main chamber portion 16 may be formed with a reduced diameter neck 72 to facilitate connection and removal of the band therefrom.
It will be apparent to one skilled in the art that variations in the details of the embodiments specifically illustrated and described may be made without departing from the true spirit and scope of the invention as defined in the claims.
1. Apparatus for dispensing a measured amount of a spray-entrapped produce for introduction into the lungs of a user, comprising an elongated passageway having a mouthpiece portion terminating at a first end and a main chamber portion terminating at a second end, said mouthpiece and main chamber portions being joined by an intermediate section, said intermediate section comprising means for supporting a metered does inhalation dispenser having a body and an extending nozzle, said intermediate section having means for directing the metered output of said dispenser into said main chamber portion and in a direction away from said first end; first and second air inlet aperture means for the introduction of ambient air into said main chamber portion for inhalation by the user, said first and second aperture means located at said second end; and valve means operatively coupled to said metered does inhalation unit for activation by movement of said metered does inhalation unit and to said second air inlet apertures, said valve means having a first position wherein said second inlet air apertures are closed and a second position wherein said second air inlet apertures are opened as said metered does inhalation dispenser is moved and activated to output into said main chamber portion.
2. The apparatus of claim 1, wherein said valve means comprises a sleeve mounted and slidable within said main chamber.
3. The apparatus of claim 2, wherein said sleeve comprises a tubular member having a first end comprising a reduced diameter passageway proximate the metered dose inhalation dispenser and a second end comprising said valve means proximate said main chamber portion second end.
4. The apparatus of claim 2, wherein said first aperture means are located in a removable cap mounted to said sleeve.
5. The apparatus of claim 4, wherein said valve is biased into said first position.
6. The apparatus of claim 4, wherein said first position is maintained by an elastic band operatively mounted between said sleeve and said main chamber portion.
7. The apparatus of claim 6, wherein said band is operatively connected to said sleeve by mounting to said cap.
8. The apparatus of claim 5, wherein said valve is operatingly coupled to said metered dose inhalation unit and said second air inlet apertures whereby said second air inlet apertures are opened prior to the time said inhalation dispenser is activated to output.
9. The apparatus of claim 5, wherein said second air inlets are adapted to restrict air flow rate to about 30 liters/minute at an inspiratory vacuum pressure of 10 cm of water.
10. The apparatus of claim 3, wherein said tubular member is of a length and diameter sufficient to receive the metered dose inhalation dispenser therein for storage purposes.
11. An apparatus for dispensing a measured amount of a spray-entrapped product for introduction into the lungs of a user, comprising an elongated, hollow passageway having a first mouthpiece end and an opposed second end; a pedestal located within said passageway adapted to receive the nozzle of a metered dose inhaler and having means to direct the spray output thereof within said passageway towards said second end; a variable air inlet means located at said second end adapted to provide a first low-flow rate of inspiratory air through said passageway at a first operative position and second higher flow rate of inspiratory air through said passageway at a second operative position; and means for repositioning said air inlet means from said first to said second position upon the commencement of the release of the spray output of the metered dose inhaler by movement of said metered dose inhaler whereby an increased inspiratory flow is created with the release of the spray whereby the spray is contacted by said flow to cause the inhalation of the spray by the user.
ES2241330T3 (en) 2005-10-16 And improvements in relation to drug delivery devices.


Experiments with photos: I'm learning how to post photos, so let's see if this works. Here's a photo from my New Year's skiing trip to Saalbach, Austria. This is my friend Matthew Coombes, although admittedly not a very good shot. (This one is better and this one is from Obertauern, a few years back.) And here's a photo of Matthew and me in London when I was made a "Freeman of the City of London" in a ceremony at Guildhall in London. Here I am with Peter Derrick, Chamberlain of the City of London.) And, while I'm at it, here's a shot of Matthew and me when visiting the Acropolis. (Visiting Athens was for me the fulfillment of a dream.) And speaking of ancient political systems, here's a photo of me at Thingvellir in Iceland, where the Icelandic Althing met. (I'm in the foreground in hiking pants. My friend Hans Eicholz of Liberty Fund is visible in the photo, and behind him is Prof. Viktor Vanberg of the University of Freiburg.) And last but not least, a photo taken by my friend Philippe Chamy while I was in Aix-en-Provence a couple of years ago. I'm going to create a permanent photo section on the site where I will have photos of various sorts.


text:
The Egyptian Journal of Otolaryngology
Imaging of metastatic cervical nodes: is CT helpful in differentiation of squamous cell carcinoma (SCC) from non-SCC groups?
Lamya A. Eissa1 &
Ahmed Mohamed Mehanna2
The Egyptian Journal of Otolaryngology volume 36, Article number: 45 (2020) Cite this article
Cervical node metastasis is frequently encountered in CT neck of patients with squamous cell carcinoma (SCC) and non-(SCC). Differentiation between both entities carries its value on prognosis and choice of treatment plans. The purpose of the study was to compare between the SCC and non-SCC metastatic cervical adenopathies according to different imaging parameters with the use of comparative statistical analysis of any of these criteria. This was made by retrospectively studying 157 patients. Imaging analyzed the following parameters: nodal size, laterality, nodal levels, "grouping" of nodes, nodal shape, and "periphery," as well as the presence or absence of nodal "necrosis." Statistics are made to show significant differences between both groups.
The criterion of necrosis had statistical significance, being more prevalent among the SCC groups. Involvement of levels I, II, and supra clavicular was more prevalent among SCC patients. Age and sex had also some statistical significance.
The combination of different imaging parameters could distinguish SCC from non-SCC. Nodal "necrosis"—(excluding "cystic")—combined with involvement of nodal levels II and being in older-aged men were statistically significant in the SCC compared to non-SCC.
Cervical lymph node metastasis is frequently encountered in CT neck examinations of patients with squamous cell carcinoma (SCC) and non-squamous cell carcinoma (non-SCC). The presence of lymph node metastasis is considered as an adverse prognostic factor in patients with head and neck cancers [1]. Dunne et al. [2] showed a near 5-year survival rates between 17 and 55.8% for SCCs with cervical node metastases compared with others between 44.6 and 76% for SCC patients without cervical node metastases [2].
Accurate identification of cervical lymph node metastases is essential for choosing the most appropriate treatment [2,3,4]. Delineation of cervical nodal metastasis is more accurately performed with imaging than with clinical palpation; imaging is widely used in both pre-treatment staging and detection of nodal recurrences.
Cross-sectional imaging, including computed tomography (CT) and magnetic resonance imaging (MRI), is routinely performed to assess the primary tumor and to examine for lymph nodes along the drainage areas of the tumor. Other imaging modalities currently used are ultrasound (US). Recently, some novel imaging techniques have been developed in attempts to improve the accuracy of the detection of nodal metastasis [3,4,5].
Multiple cross-sectional criteria have been developed to diagnose metastatic disease [5]. Nodes (JD) are considered to be metastatic if central necrosis or extracapsular spread is present irrespective of size, or if the shortest axial diameter reaches 11 mm in the jugulodigastric nodes and 10 mm in other cervical regions [6,7,8]. The sign "grouping" or clustering is also used. These signs are applied if there is a group of 3 or more nodes in a drainage region of a certain primary cancer [6,7,8]. The sign of clustering signifies an adverse predictive outcome and appears to be especially prevalent in head and neck cancer, mostly in squamous cell carcinoma SCC deposits [9,10,11]. Regarding the sign of shape, round nodes or those with lost fatty hila are also more likely to harbor metastases than oval bean-shaped nodes [12,13,14,15]. Although shape criteria by imaging were mainly designated for the context of enlarged nodes, nearly 82-86% of metastatic lymph nodes may be round but less than 10 mm Therefore, although roundness alone does not necessarily points out to metastasis [16].
A fourth imaging criterion is Inhomogeneity or central necrosis. Central necrosis is the imaging finding that is most reliably associated with metastasis and is reported to be present in nearly one-third of all metastatic cervical lymph nodes. In the setting of head and neck cancer, a necrotic node is considered pathologic regardless of size and can be seen in sub-centi-metric nodes [11, 12, 15]. Another imaging criterion to be considered is the presence of nodal enhancement. The nodal hyper-enhancement implies an increase in nodal vascularity. These hyper-enhancing nodes can be undermining a variety of hyper-vascular neoplasms as lymphoma, papillary, and medullar thyroid carcinoma, and Kaposi sarcoma. Differentiation from other non-neoplastic hyper-vascular nodes needs constellation of other imaging criteria, which may be similar or not to those implied in SCC nodes. Besides intense enhancement, intra-nodal calcifications, either coarse or punctate (in 50–69%), and cystic changes (20%) may be noted. In larger tumors, a CT scan may show a thyroid mass invading adjacent structures (trachea, esophagus) [16,17,18,19,20].
To the best of our knowledge, our research is only the second in English literature trying to discuss the role of enhanced neck CT in differential diagnosis between SCC and non-SCC using comparative statistical analysis, comparing variables obtained from some of the abovementioned imaging criteria. SCC is the most common pathological type found in cervical lymph node metastasis followed by adenocarcinoma, the latter is the most common histological type in cervical lymph node metastasis from non-SCC. The purpose of our study was to assess the differential imaging findings of metastatic lymph nodes in SCC and non-SCC on neck CT and to facilitate the identification of primary focus before performing a biopsy and tailoring the most appropriate imaging plan when certain occult is suspected.
Description of the retrospective study
All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation "Institutional Review Board (IRB)" on the 14th of February 2017, and with the Helsinki Declaration of 1964 and later versions. The Committee's reference number is unavailable (not applicable). No consent was obtained from the patients since it was a retrospective study.
Selection of patients, inclusion and exclusion criteria
We retrospectively analyzed 157 patients (90 men, 67 women, and mean age 60 of age range between 17-90 years). The study was meant to include the adult ages of both sexes. Primary and recurrent post-operative cases, as well as post-irradiated head and neck cancers (more than 3 months from last radiation session) were included. Also, patients with known suggested primaries of head and neck or any other site of the body were included. The study excluded the following: patients with recent radiation history < 3 months from last radiation session (to avoid masquerading changes of radiation), patients with lymphoma, prior recent FNC or any surgical interventions, and patients with signs of suggestive of inflammatory process. Also, patients with proven or suggested TB of the chest are excluded (refer to Table 1 on distribution of nodal groups with demographic data).
Table 1 Distribution of pathologies among two groups of patients
Sites of primaries
The number of SCC patients was 94 (59.9%), and the number of non-SCC patients was 63 (40.1%). The patients underwent a dedicated neck CT from April 2017 to April 2019. Of those 139 (88.5%) had primary cancers originating from a head and neck sub-site, while 18 (11.5%) had primary cancer outside the head and neck regions. SCC malignancies were distributed as follows: oral cavity = 13 (13.8%), oropharynx = 4 (4.3%), hypopharynx = 37 (39.4%), NPC = 3 (3.2%), larynx = 15 (16%), lung = 8 (8.5%), skin = 8 (8.5%), laryngectomy beds = 4 (4.3%), others = 2 (2.1%) including two SCCs of scalp. The non-SCC carcinomas include the following: oral cavity = 9 (14.3%), including 7 melanomas and 2 adenocarcinomas, thyroid = 36 (57.1%), oropharynx = 5 (7.9%), NPC = 2 (3.2%), made of two adenocarcinomas, sino-nasal = 2 (3.2%), lung small cell cancer = 1 (1.6%), and skin melanoma = 1 (1.6%), 7 (11.1%). These others include one testicular, one ovarian, four breasts, and last one unknown (adenocarcinoma) (please refer to summary of distribution of primary sites as compared to SCC and non-SCC at Table 2).
Table 2 Comparison between the two studied groups according to demographic data
Oral cavity patients had selective neck dissection while others underwent incisional biopsies of most suspicious node (methods included direct FNC or US guided). However, needle biopsies were not correlated to open surgical results.
Imaging examination technique
All CT scans were performed with 128-multi-channel (Toshiba-Aquillion). Scanning parameters were as follows: 1 table pitch, 120 kVp, 140 mAs, and 1.5 mm thickness. A 100 mL of nonionic contrast material (Omnipaque 350 mg/ml) was injected at by a bi-phasic mode of injection followed by a 20 mL saline flush.
Imaging analysis
A head and neck radiologist with 12-year experience in head and neck radiology subspecialty reviewed two sets (SCC and non-SCC) of neck CT. The task was to assess the characteristics of the abnormal lymph nodes (number, margin types, enhancement patterns, size, bilaterality, necrosis, and grouping).
The following imaging criteria were evaluated:
Laterality: unilateral (ipsilateral or contra-lateral) versus "bilateral" versus "midline" disease is reported.
Node size: this is reported in axial plane measuring both short and long-axis diameter encompassing the outer margins.
"Levels" and "groups" of nodes involved: nodal grouping and levels according to known classification, adopted by "site Classification for Lymph Nodes From American Head and Neck Society and American Academy of Otolaryngology-Head and Neck Surgery" [21, 22].
Periphery/margin of nodes: these are reported as "irregular" versus "regular." No comment was made on extra-capsular margins as this hard to correlate with biopsy after operative excision.
Shape of the node: these include rounded, oblong, oval, and oval to oblong. The rounded node is defined as that node having a long-to-short axis ratio of less than 2 mm. The oblong node is having a long-to-short axis ratio of more than 2 mm and more prominent in appearance than oval, while the oval is the normal expected pea-shaped node with or without loss of margin.
Grouping/clustering of drainage nodes: this image criterion is coined to multiple involved nodes; groups of > 3 lymph nodes at any given nodal drainage level. The grouped/clustered nodes are further sub-classified into "conglomerate" versus "non-conglomerated" nodes. Conglomeration of lymph nodes was considered as juxtaposed lymph nodes; nearly sharing stuck-together walls that cannot be clearly delineated from each other with effacement of intervening fat.
Presence or absence of necrosis: necrosis is defined as the presence of intra-nodal identified > 2 mm internal hypo-density, showing a near water attenuation on CT (10-25 HU). Even few small foci in an essentially solid node will make this node termed a necrotic node. As regards the necrosis, the nodes are further sub-classified into (A) "Necrotic", (B) "non-Necrotic," and (C) "Cystic." These are further evaluated as follows:
The necrotic nodes are further analyzed as regards the following imaging criteria related to the necrosis, including the following (summarized in Fig. 1):
The epi-center of necrosis within nodal substance: central versus peripheral.
Thickness of margin of necrosis within the node is defined as thin < 1 mm, thick 1-3 mm; very thick > 3 mm.
The inner margin of necrosis is defined as regular versus irregular.
Heterogeneity versus homogeneity: the necrosis itself is considered as heterogeneous if any of these criteria is seen: septa, debris, globulin, calcifications, or nodules.
The enhancement of this peripheral margin:
Iso-enhancement if near to the attenuation of head and neck muscles
Mild to moderate hyper-enhancement (> muscle and < thyroid)
Very hyper-enhancing: equal to or above thyroid or vessel enhancement
Non-necrotic lymph nodes were further sub-classified according to "Homo/Heterogeneity" of enhancement, as those showing homogeneous or heterogeneous enhancement. "Degree of enhancement" of the node is sub-classified as follows: (1) iso-enhancement if near to the attenuation of head and neck muscles, (2) moderate hyper-enhancement is higher than muscle and less than thyroid, (3) very hyper-enhancing: equal to or above thyroid and vessel enhancement.
Cystic nodes: The term cystic is confined only to near wholly necrotic nodes with near homogenous pure fluid attenuation and thin < 0.1 mm nodal margin or even imperceptible. These are analyzed further into presence or absence of calcification or solid nodules.
A case of retro-molar molar trigone squamous cell carcinoma (yellow arrow in " a"), with associated metastatic necrotic nodes at level II (b), showing thin peripheral margin and is not termed cystic in our study. This shows thin rim with regular margin. Other nodes are more solid with tiny necrotic foci and moderate hyperenhancement (c). The features are all in favor of squamous cell carcinoma node
Statistical analysis of the data
Statistical analysis of the data with comparison of imaging variable between SCC and non-SCC nodal groups: data were fed to the computer and analyzed using the IBM SPSS software package version 20.0 (Armonk, NY: IBM Corp). Qualitative data were described using number and percent. Kolmogorov-Smirnov test was used to verify the normality of distribution. Quantitative data were described using range (minimum and maximum), mean, standard deviation, and median. The significance of the obtained results was judged at 5% level. The used tests were (1) chi-square test for categorical variables, to compare between different groups, (2) Fisher's exact or Monte Carlo correction, (3) Student's t test.
Regarding the laterality of nodes, the majority of 131 (83.4%) had unilateral disease, only two of them had isolated contra-lateral disease in two patients with oral cavity primary. Bilateral disease was seen in 23 (14.6%). Isolated midline disease was seen in only 3 (1.9%), two of them had single Delphian nodes in thyroid cancers, and a single midline sub-mental node was also observed in oral cancer case.
As expected, the jugulodigastric-JGD (level II) nodes had the greatest burden disease being involved in the highest ratio of patients (92 patients IIA and 63 for IIB, representing = 58.6% and 40.1% respectively). These nodes represent the sentinel nodes of head and neck cancer. All involved nodes came from primary head and neck cancers apart from single cases of breast cancer with extensive supra-clavicular and deep cervical nodes. Level I nodes had the second-highest prevalence, counted as 57 (36.3%) for IA and 25 (15.9%) for level IB. Their primaries are prevalent in the oral cavity (oral tongue, gingiva, and alveolar margin). Level III nodes had the third-highest prevalence, 57 (36.3%), usually noted in association with level II nodes, and not in isolation.
Level IVA was seen in 15 cases (9.6%) and level IVB in 30 cases (19.1%). Those were never seen isolated. They were involved in thyroid cancer in combination with levels III and supra clavicular or with level II (JDG) in the oral cavity and oropharynx after crossing the sentinel II nodes. Level V was involved in 12 (7.6%), 4 were in the five cases of NPC, a single case atypically involved in oropharyngeal mass with extensive deep cervical adenopathies, 4 were thyroid cancers, and the remainder are primaries outside the head and neck regions.
Level VI nodes were involved in 12 patients (7.6%), seen exclusively in visceral space malignancies (i.e., thyroid). Parotid nodes were involved in 5 (3.2%), all of which originated from superficial tumors (skin). Isolated para-pharyngeal space adenopathies were seen in 4 (2.5%), all had primary thyroid cancers. Retropharyngeal adenopathies were never seen in isolations. These were involved in 12 (7.6%); they were seen in oropharyngeal, NPC, sino-nasal, and thyroid cancers. The supra clavicular had high prevalence, seen in 26 patients (16.6%): these involved all the 18 patients with primaries outside the heads and neck regions. However, the thyroid gland had the highest prevalence of supra-clavicular metastatic nodes and was always involved with level III or IV nodes in the same patient. Delphian node was involved in 8 patients; all had primary thyroid cancer.
Comparing nodal level and group involvement between SCC and non-SCC revealed: Involvement of JGD, sub-mental, and supra-clavicular nodes had statistically significant difference among SCC and non-SCC groups. This is well expected as JGD represents the nodal sentinel drainage of upper aero-digestive SCC lesions mostly represented by the oral cavity and oropharynx. The involvement of level II was shown in 67 (71.3%) of SCC groups compared to 25 (39.7%) in non-SCC, while level IIB was seen in 41 (43.6%) compared to 22 (24%). A key difference between both groups is that involvement of level IIA/B in SCC could occur solely or in combination with level I or less likely with more caudal nodal levels. On the other hand, involvement of level IIA/B in non-SCC always occurred in combination with other more caudal "sentinel" levels including III, IVA/B, and supra-clavicular nodes. Involvement of supra-clavicular nodal groups also had statistical significance between both groups, being higher in non-SCC groups (15 (23.8%)) as compared to 11 (11.7%) in SCC groups (Table 3 shows laterality, nodal levels, and groups involved).
Table 3 Comparison between the two studied groups according to distribution (laterality and nodal level)
The study showed multiple-nodal involvement in 94 (59.9%) of total 157 cases, as compared to 63 (40.1%) of single-nodal involvement. Out of the "multiple nodal Involvement," the sign of "grouping" was seen in 69 cases: 56 (59.6%) showed grouping without conglomeration, while 13 (13.8%) showing grouping and conglomeration. Six out of conglomerated nodes (total are 13) had primary thyroid cancers while others had primaries of oral cavity, oropharynx, and hypo-pharynx as well as single case of testicular cancer (non-SCC). The non-grouping was seen in 25 (26.6%). The "grouping" of nodes usually points to metastatic nature. However, this sign of grouping plus or minus conglomeration had no statistical significance among the SCC and non-SCC groups (Table 4). Figures 2, 3, 4, 5, and 6 show illustrated cases of SCC and non-SCC metastatic nodal groups and how constellation of described imaging criteria is used in combination to differentiate the two categories on CT basis.
Table 4 Comparison between the two studied groups according to different imaging parameters
A case of 82-year-old male patient with hypopharyngeal squamous cell carcinoma. This is associated with right-sided necrotic nodes at IIB and III. They show central necrosis at the largest node with a very thick irregular margin showing slight "hyper-enhancement," and grouping non-conglomerated appearance. (a) Shows the main tumor and nodal disease at two levels, while (b) image shows the longitudinal tumor. The features of "necrosis" are consistent with squamous cell carcinoma metastatic node according to our study
A 34-years-old man with cystic node on right side: (a) showing homogenous cystic node as coined in our study (b) showing moderately hyper-enhancing nodules (yellow arrow). Both nodal components are shown in the coronal image in (c) and a necrotic node is seen at level IV at (d). Imaging suggested non-squamous cell carcinoma metastatic node and thyroid primary highly suspected though not shown at all on computed tomography. Ultrasound-guided biopsy confirmed papillary thyroid carcinoma
A case of 63-year-woman of prior old (10 years ago) of operated thyroid cancer with multiple questionable cervical nodal swellings. (a) Shows clear thyroidectomy bed. (a and b) Shows grouped bilateral markedly necrotic nodes with smooth regular iso to mild hyper-enhancing smooth and thin margin, at levels II mainly with grouping and near conglomeration. A right-sided retropharyngeal node is seen (c). Features are in favor of being squamous cell carcinoma metastatic nodes over the non-squamous cell cancer nodes, putting down the possibility of thyroid recurrence. (d) Shows the primary oropharyngeal primary squamous cell carcinoma proved later. The signs helped to differentiate a new squamous cell carcinoma metastatic node and not a non-squamous cell "thyroid" metastatic node regarding the history of operated thyroid cancer
A case of 67 years old of nodal recurrence from previous de-differentiated thyroid carcinoma. A very huge invasive node on right side with marked necrosis (a); essentially not central and very thick hyper-enhancing irregular margin and small non-necrotic IV node on left side (b), showing moderate to very hyper-enhancement
A 25 years old female with asymmetric thickening of nasopharyngeal recess in a proven NPC (a) and necrotic SSC node at nodal level II on the left side (b)
Necrotic nodes as defined in our study showed higher prevalence among metastatic nodes in both groups constituting a total of 107 (68.2%) of the total case toll, as compared to "non-necrotic" solid nodes 31 (19.7%), and "cystic" nodes 19 (12.1%). The necrosis was almost central in the highest majority of cases (95.3%). Margins of necrosis with different thickness and regularities were evaluated: combination of thick and irregular margin had the highest incidence of 49 (45.8%) among the total number of cases, followed by thick regular margin (29.9%). Heterogeneity of necrosis itself had prevalence over homogenous ones (72%). Statistical comparison between SCC and non-SCC groups showed that the criterion of necrosis itself was statistically significant in SCC as compared to non-SCC (n = 74: 78.7%) in SCCs compared to (n = 33: 52.4%) in non-SCC. The rim of enhancement around the necrosis was mostly iso-enhancing in SCC nodes, as compared to non-SCC (hyper to very hyper). This sign also had some statistically significant difference (Table 5).
Table 5 Comparison between the two studied groups according to different parameters: margins and shape
Cystic nodes had a very good statistical significance among both groups: They were found in 3 (3.2%) of SCC patients, and in 16 (25.4%) of non-SCC patients. The SCC cystic nodes had prevalence in oral cavity nodes while non-SCC cystic nodes were mainly from thyroid primaries, apart from single testicular cases. However, intrinsic imaging details of a cystic node can adequately separate thyroid form non-thyroid metastatic adenopathies. Thyroid papillary nodes show with cystic nodes showed combination with one of two: calcification and/or moderate or very hyper-enhancement in mural nodules or peripheral perceptible rims. The medullary and anaplastic metastatic nodes in our study showed mainly non-necrotic solid adenopathies with variable degrees of mild to very hyper-enchantment.
Non-necrotic nodes had no statistical significance between the two groups, counted as 17 (18.1%) in SCC nodes compared to 14 (22.2%) in non-SCC nodes. Still, intrinsic imaging criteria of solid non-necrotic nodes have not been detailed in our study. Still, solid metastases of thyroid primaries had variable degrees of hyper-enhancement (mild to very hyper-enhancement). The periphery of nodes was mostly regular (73 (77.7%)) of SCC and 48 (76.2%) in non-SCC. This shows that marginal irregularity is not highly prevalent in metastatic nodes altogether, in contra-distinction to non-neoplastic inflammatory nodes where peri-nodal inflammation and peri-adenitis is usually prevailing (Table 6).
Table 6 Comparison between the two studied groups according to grouping
To the best of our knowledge, only a single previous published research has discussed the role of enhanced neck CT in differentiation between SCC and non-SCC metastatic nodes. This was made by Lee NY et al. [23] who performed a similar retrospective study on a slightly smaller sample of patients including a total of 105 patients, encompassing both SCC and non-SCC groups. In their study, the SCC patients constituted a smaller percentage of 46 patients compared to 50 SCC patients. In contrary, our study had much higher SCC patients 94 (59.9%), as compared to non-SCC 63 (40.1%). This was nicely expected in view of the common incidence of head and neck SCC, being the most common histopathological subtypes. They included sites outside the head and neck (breast, cervix, gall bladder, prostate and colon, and single case of unknown primary). Our patients with distant sites included primaries of lung, breast, ovaries, testes, esophagus, and a neuro-ectodermal tumor as well as a single unknown primary adenocarcinoma. These constituted 18 (11.5%) of the total study cases [23].
In their study, patients in the SCC group (36–89 years, mean: 63.0 years) were significantly older than those in the non-SCC group (16–81 years, mean: 56.1 years). This was in good correlation with our study: the SCC patients were older (64 (21–90 years), compared to non-SCC group 47 (17–86 years). In their study, Lee et al. [23] stated that various primary cancers were included in this study with a high proportion of young thyroid cancer cases in the non-SCC group (22/50) correlated to this result. However, in our study, this was not the case since our thyroid cases include old-onset papillary carcinomas and anaplastic variant. Still, the oldest of patients of SCC occupied primaries of lung, oropharynx, hypopharynx, and larynx (> 60 years of age) [23].
In their study, Lee et al. [23] stated that SCC was more frequent in men than in women (female to male ratio, 11:35) and non-SCC was relatively more frequent in women than in men (female to male ratio, 29:21). Our study also showed similar results, SCCs had prevalence in males (76.6%), while the non-SCC had prevalence in females (60.3%). Thyroid cancer was noted in 22 patients out of 50 non-SCCs in their study, as compared to 36 out of 36 non-SCCs in our study. Thyroid cancer was much more frequent in females than in males (female to male ratio, 18:4). In our study, thyroid cancer was also much more frequent in females than in males (female to male ratio, 19:7). In the previous reports by Muir et al. [24] and Voutilainen et al. [25] stated that the female-to-male ratio of thyroid cancer ranged from 2:1 to 5:1 in most populations [23,24,25].
In the study by Lee et al. [23], the number of lymph nodes in the non-SCC group and the number of lymph nodes smaller than 3 cm were greater than those in the SCC group. They reported a statistically significant difference between the SCC group and the non-SCC group except for cases of thyroid cancer. In our study, the measurement of nodal size was made only as part of routine work and not meant for being part of statistical analysis. However, a total of 39 patients had nodes greater than 3 cm in maximum axial diameter, 20 of them were SCC patients. The four cases in our study having > 6 cm longest axial diameter was seen in 3 non-SCC compared to single SCC. Evaluation of nodal size as part of characterization of nodal metastases or differentiation of SCC from non-SCC needs larger patient samples with trial to separate thyroid patients [23].
The nodal levels of IA and IB had statistical significance between the two groups. These are nearly solely involved in oral cavity and oropharyngeal cancers with or without upper deep cervical nodes (jugulodigastric-JDG nodes). These would not show isolated involvement in cases of thyroid cancers without more caudal deep cervical nodes. Also, levels IVB and supra-clavicular nodes showed statistical difference, being involved in most of thyroid cancers with variable involvement of level VI, Delphian, or III. Isolated Delphian node involvement is nearly pathognomonic in thyroid cancers. Unexpectedly, the involvement of level VI had no statistical significance between the SCC and non-SCC. This could be attributed to the fact that the study included primary and post-operative cases. The operated cases as laryngectomies (SCC) may have non-regional nodal deposits at level VI due to altered and inter-mixed lymphatics following surgical dissections. However, the exclusive involvement of VI in the primary presentation of cervical nodal metastasis points to visceral space, non-SCC malignancy mostly of thyroid cancer.
The study of the criterion of grouping as a sign of malignancy in nodes revealed no statistical significance between the two groups. Grouping with conglomeration was seen in 30 (58.8%) of SCC patients, compared to 26 (60.5%) of non-SC groups. While grouping without conglomeration was seen in 6 (11.8%), compared to 7 (16.3%) of the non-SCC. This was attributed to the fact that conglomeration was seen in oral cavity SCC metastatic nodes and some types of thyroid cancer nodal metastases. This was in disagreement with results by Lee et al.; they coined the term of conglomeration to be equivalent to the description of simple grouping in our stud. They show statistical significance, being more commonly and more frequently observed in the SCC group (55.6%) than in the non-SCC group (44.4%). Conglomeration and grouping are used synonymously in literature; it is described as grouping of at least three lymph nodes and has been used as a morphologic criterion for the diagnosis of SCC of the head and neck region [26].
Previous reports have demonstrated that the detection of intra-nodal necrosis in patients with primary head and neck tumors is the most reliable sign of being a metastatic node [24, 27]. Necrosis is frequently seen in nodal metastases from SCC of the head and neck, and it was used for differentiation form in non-metastatic nodes [8, 28, 29]. In the study by Lee NY et al. [23], they revealed no significant difference in the presence of necrosis between the two groups. In disagreement with their study, ours revealed good statistical significance of the sign of necrosis between the two groups, showing high prevalence between the two groups, occurring in 74 (78.7%) of the SCC patients compared to 33 (52.4%) of non-SCC. A good explanation for this disagreement is that their study did not separate the cystic form necrotic nodes. In our study, cystic nodes are considered as a separate group and are further sub-classified according to combination with fine calcifications and hyper-enhancing wall or nodules. Please refer to Figs. 2, 3, 4, 5, and 6 for comparison of nodal groups.
When analyzing the intrinsic details of nodal morphology regarding nodal necrosis, our study tried to analyze different combinations of marginal thickness and smoothness versus regularities. The combination of thick margin with either regularity or irregularities had the highest prevalence between the two groups. Similarly, Lee et al. [23] pointed out that there was no significant difference in the ratio of lymph nodes with thick irregular wall enhancement to total lymph nodes between the SCC group and the non-SC group except for cases of thyroid cancer.
Our study had several limitations. First, the total sample size, though larger than our preceding example made by Lee et al. [23], still larger group of patients could give more significant statistical results. Second, this is a retrospective review of patients who underwent imaging investigations as part of the assessment for head and neck metastasis. Third, pathological confirmation by operative biopsy was not achieved in all patients. Fourth, thyroid cancer metastatic nodes are supposed to have distinct features among the non-SCC and these are recommended for further evaluation in separate consideration and in larger group of patients.
In conclusion, a combination of metastatic-looking adenopathies in certain nodal groups could suggest underlying squamous cell carcinoma or non-squamous cell carcinoma. Nodal necrosis, separating the "cystic" group, and involvement of nodal levels II and I in isolation from caudal deep cervical nodes in older aged men; both were statistically significant in the SCC compared to non-SCC. Though not showing statistical difference, the grouping +/− conglomeration and multiple or non-single nodal group/level involvement could show statistical significance with larger study size and separation of thyroid metastatic group.
The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
SCC:
Non-SCC:
Non-squamous cell carcinoma
MRI:
Hounsfield unit
NPC:
Naso-pharyngeal carcinoma
Seethala RR (2009) Current state of neck dissection in the United States. Head Neck Pathology 3:238–245
Dunne A, Muller HH, Eisele DW, Kebel K, Moll R, Werner JA (2006) Meta-analysis of the prognostic significance of per nodal spread in head and neck squamous cell carcinomas (HNSCC) patients. Eur J Cancer 42(12):1863–1868
Snow GB, Patel P, Leemans CR, Tiwari R (1992) Management of cervical lymph nodes in patients with head and neck cancer. Eur Arch Otorhinolaryngol 249:187–194
Brown AE, Langdon JD (1995) Management of oral cancer. Ann R Coll Surg Engl 77:404–408
Miller JE, Al-Attar NC, Brown OH, Shaughness GG, Rosculet NP, Avram AM, Hughes DT (2018) Location and causation of residual lymph node metastases after surgical treatment of regionally advanced differentiated thyroid cancer. Thyroid 28:593–600
Johnson J (1990) A surgeon looks at cervical lymph nodes. Radiology 175:607–610
Ng SH, Ko SH, Toh CH, Chen YL (2006) Imaging of neck metastases. Med J 29(2):119–126
Brekel MW, Stel HV, Castelijns JA, Nauta JJ, van der Waal I, Valk J, Meyer CJ, Snow GB (1990) Cervical lymph node metastasis: assessment of radiologic criteria. Radiology 177:379–384
Imhof H, Czerny C, Dirisamer A (2003) Head and neck imaging with MDCT. Eur J Radiol 45:23–31
Curtin HD, Ishwaran H, Mancuso AA, Dalley RW, Caudry DJ, McNeil BJ (1998) Comparison of CT and MR imaging in staging of neck metastases. Radiology 207:123–130
Som PM (1992) Detection of metastasis in cervical lymph nodes: CT and MR criteria and differential diagnosis. AJR Am J Roentgenol 158:961–969
Lee KJ, Kirsch C, Sayre J (2008) Lymph node clustering in head and neck squamous cell cancer. Otolaryngol Head Neck Surgery 139:38–40
Stoeckli SJ, Pfaltz M, Steinert H (2002) Histopathological features of occult metastasis detected by sentinel lymph node biopsy in oral and oropharyngeal squamous cell carcinoma. Laryngoscope 112:111–115
Xu C, Liu Y, Wang P (2010) Integrative analysis of DNA copy number and gene expression in metastatic oral squamous cell carcinoma identifies genes associated with poor survival. Mol Cancer 9:143
Kuna SK, Bracic I, Tesic V (2006) Ultrasonographic differentiation of benign from malignant neck lymphadenopathy in thyroid cancer. J Ultrasound Med 25:1531–1537
Dmytriw AA, El Beltagi A, Bartlett E, Sahgal A, Poon CS, MD FR, Fatterpekar G, Yu E (2014) CRISPS: a pictorial essay of an acronym to interpreting metastatic head and neck lymphadenopathy. Can Assoc Radiol J 65:232–241
Som PM, Brandwein M, Lidov M (1994) The varied presentations of papillary thyroid-carcinoma cervical nodal disease: CT and MR findings. Am J Radiol Neuroradiol 15:1123–1128
Cheng F, Yanyan C, Zhu L, Zhou B, Younghong Y, Chen Y, Wen C, Chen S (2019) Risk factors for cervical lymph node metastasis of papillary thyroid microcarcinoma: a single-center retrospective study. Int J Endocrinol 8:1–6
Karandikar A, Gummalla KM, Loke SC, Goh J, Tan TY (2016) Approach to intensely enhancing neck nodes. Diagn Interv Radiol 22:168–172
King AD (2008) Imaging for staging and management of thyroid cancer. Cancer Imaging 8:57–69
Hoang J, Benjamin JV, Ludwig J, Glastonbury CM (2013) Evaluation of cervical lymph nodes in head and neck cancer with CT and MRI: tips, traps, and a systematic approach. Am J Radiology 200:17–25
Som P, Curtin H, Mancuso A (2000) Imaging-based nodal classification for evaluation of neck metastatic adenopathy. Am J Radiol 174:837–844
Lee NY, Han JK, Kim HW, Shin HC, Kim YK, Jou SS (2015) Comparative study of lymph node metastasis from squamous cell carcinoma and non-squamous cell carcinoma on neck CT. J Korean Soc Radiol 72(4):271–281
Parkin DM, Muir CS (1992) Cancer incidence in five continents. Comparability and quality of data. IARC Sci Publ 120:45–173
Voutilainen PE, Multanen MM, Leppäniemi AK, Haglund CH, Haapiainen RK, Franssila KO (2001) Prognosis after lymph node recurrence in papillary thyroid carcinoma depends on age. Thyroid 11:953–957
Dammann F, Horger M, Mueller-Berg M, Schlemmer H, Claussen CD, Hoffman J (2005) Rational diagnosis of squamous cell carcinoma of the head and neck region: comparative evaluation of CT, MRI, and 18 FDG PET. Am J Roentgenol 184:1326–1331
Mancuso AA, Harnsberger HR, Muraki AS, Stevens MH (1983) Computed tomography of cervical and retropharyngeal lymph nodes: normal anatomy, variants of normal, and applications in staging head and neck cancer. Part II: pathology. Radiology 148:715–723
Yousem DM, Som PM, Hackney DB, Schwaibold F, Hendrix RA (1992) Central nodal necrosis and extracapsular neoplastic spread in cervical lymph nodes: MR imaging versus CT. Radiology 182:753–759
King AD, Tse GM, Ahuja AT, Yuen EH, Vlantis AC, Te EW (2004) Necrosis in metastatic neck nodes: diagnostic accuracy of CT, MR imaging, and US. Radiology 230:720–726
This study had no funding from any resource (none).
Department of Diagnostic and Interventional Radiology, Alexandria Faculty of Medicine, Alexandria, 21131, Egypt
Lamya A. Eissa
Department of Oto-rhino-laryngology, Alexandria Faculty of Medicine, Alexandria, Egypt
Ahmed Mohamed Mehanna
AM provided the cases and final diagnoses, with detailed description of results. LE gave the idea, wrote the section of introduction, and provided the whole references for introduction and discussion with making of figure legends. "All authors read and approved the final manuscript."
Correspondence to Lamya A. Eissa.
All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation "Institutional Review Board (IRB)" of Alexandria General Hospital on the 14th of February 2017, and with the Helsinki Declaration of 1964 and later versions. The committee's reference number is unavailable (not applicable). No consent was obtained from the patients since it was a retrospective study.
All patients included in this research gave written informed consent to publish the data contained within this study.
Eissa, L.A., Mehanna, A.M. Imaging of metastatic cervical nodes: is CT helpful in differentiation of squamous cell carcinoma (SCC) from non-SCC groups?. Egypt J Otolaryngol 36, 45 (2020). https://doi.org/10.1186/s43163-020-00045-x
Received: 27 March 2020
DOI: https://doi.org/10.1186/s43163-020-00045-x

redpajama_set_name: RedPajamaCommonCrawl


text:
Good vibrations (Musings on new research on idiopathic pulmonary fibrosis)
Updated: 27 Dec. 2014
This new blog is to relate what I discovered
When generous friends wrote Alberta's then Health Minister, Fred Horne asking for Esbriet to be funded for idiopathic pulmonary fibrosis (IPF), including Minister Horne's response when I contacted him directly.
Interesting tidbits from additional medical research on IPF.
How physicians vary in their approach to patients with IPF.
*** Plus - and it's a huge plus - a surprising update in early December (see blog's new ending).
In 2013 my spouse was diagnosed with IPF, a deadly disease with no known cure and a median life expectancy after diagnosis of ~3 years.
Besides the diagnosis, it was a shock to learn that the one known treatment at the time (pirfenidone / Esbriet) was approved for use by Health Canada, but not funded by provincial governments.
I subsequently read many scientific papers on the issue and wrote 4 blogs that examined what it's like to get an IPF diagnosis and why Esbriet is covered by public funding in the UK but not Canada. In brief, reasons include
The Canadian Drug Expert Committee (CDEC), under the auspices of CADTH, decided that Canada should not fund Esbriet (18 April, 2013).
The clinical trial results at the time were equivocal and CDEC opted for seeing the glass half empty, no doubt partly because Esbriet is expensive ($40,000 - $50,000/yr). Provinces would prefer not to pay for a drug that slows, but does not cure IPF, a disease affecting mainly the elderly.
To access the 4 earlier blogs on IPF: 'While my guitar gently weeps' (Musings on idiopathic pulmonary fibrosis).
Although we are fortunate to have great health insurance, it did not cover a drug as expensive as Esbriet. We understand why our drug maximum is $2000/yr, otherwise the plan would be unsustainable.
HOW GOVERNMENT RESPONDS
Many friends kindly wrote the Alberta government, usually the Health Minister, Premier, or their MLA, using a variation of the Canadian Pulmonary Fibrosis Foundations' provincial advocacy packages. Regardless of how personalized they made their appeals - including that they knew the UK but not Canada funded Esbriet - in return all, including me, received what amounted to a government form letter, which totally ignored the content of our letters.
In return I wrote Minister Horne and asked him to cut the crap and reply to 3 simple questions.
To his credit, Fred Horne replied to my direct questions. If I interpret Minister Horne's reply correctly:
Unless CDEC recommends Esbriet funding, Alberta won't fund it.
Alberta's expert committee (ECDET) accepts (rubber stamps) CDEC's decisions.
Forget about Alberta's Short Term Exceptional Drug Therapy (STEDT), unless a drug is approved for public funding by CDEC OR Canada's provinces negotiate what they deem a reasonable cost for Esbriet.
Alberta Health's replies were as expected. I just wish the government would be more transparent and upfront, instead of giving citizens the hope that maybe you can get your expensive drug, with unknown or iffy efficacy, under special funding.
Maybe you can, but only if you are a cute child with a rare disease or if your disease is more common (e,g., cancer), thereby involving more voters. Cynicism or reality? You judge.
WHAT RESEARCH SAYS
Since I wrote the prior blogs, new research has emerged on Esbriet's value in treating IPF, notably,
IPF now a treatable disease (CMAJ)
Two drugs reduce the progression of IPF
In 2014 The Journal of the American Medical Association (JAMA) reported that pirfenidone (Esbriet) reduced the relative risk of death or disease progression by 43% compared with placebo.
Accordingly, CADTH is looking at another submission on pirfenidone (Esbriet) and seeks input.
In the meantime, Esbriet's maker, Intermune was bought by Big Pharma's Roche for $8.3 billion, likely in the hope that the U.S. FDA will approve Esbriet for use in the USA. Effects of the takeover on Esbriet's public funding in Canada remain to be seen.
A TALE OF TWO PHYSICIANS
My spouse's initial lung specialist (pulmonologist / respirologist) is a physician with much experience, who gave Peter hope that he could get funding for Esbriet, which might significantly help, although not cure, his IPF. The doc patiently spent much time explaining IPF and its possible clinical courses.
He put us in touch with Esbriet's maker to investigate if our insurance would pay. He submitted Peter's name to Alberta's Short Term Exceptional Drug Therapy program (STEDT).
But he soon moved his practice outside our city to what is often called a 'bedroom community'. Although relatively close, driving is a challenge and I could not see travelling there for continuing care.
Unfortunately, we quickly learned that Esbriet funding was a no-go (as explained above in correspondence with Fred Horne). The original respirologist was hopeful that it would eventually be funded, especially if enough people drew the Minister's attention to the issue of IPF and Esbriet / pirfenidone. Thus, we asked friends to write the Health Minister.
In a pulmonary care exercise program with an Edmonton primary care network, we were told that IPF could deteriorate quickly at any time (acute exacerbation), and we needed a physician to manage it. We opted for a respirologist who was younger and therefore the wait time to see her was less and was affiliated with the University of Alberta Hospital, the facility closest to us.
Her approach was caring but more or less 'all business' and straight forward.
She reassured Peter not to worry about no Esbriet funding. The drug is not a cure for IPF and has significant side effects.
Her approach was, Let's take a few key tests (lung function, echocardiogram, CT scan, 6 minute walking test, review earlier sleep apnea test results) so that she could assess his current medical condition.
Then she would discuss where he was at and treatment options.
We appreciated this approach: Let's assess the current state of the disease. What can we do, if anything?
LEARNING POINTS
Some of the key things we've learned:
1. Public advocacy programs for government funding of expensive drugs to treat incurable diseases are worthwhile but work better under certain circumstances.
Many voters are mobilized to advocate the cause.
Helps, but does not guarantee success, if
Celebrities participate
Disease is common
Victims pull at heart strings
2. Government funding of drugs is shrouded in smoke and mirrors.
Health Canada approval does not equal provincial funding.
Governments seem content to let advocates 'piss in the wind' and only fess up to reality when pressed.
Provincial exceptional drug therapy programs to fund high cost drugs for rare conditions do not apply to drugs unapproved for funding by CADTH's CDEC. [Except perhaps for children with heart-wrenching diseases like this little girl.]
3. Lung specialists vary in their approaches to dealing with patients with life-threatening, incurable diseases.
One approach does not fit all because communication involves a communicator (Dr.) and a recipient (patient), and recipients vary greatly in their ability to accept harsh facts.
In our case a reality-based approach is okay.
4. Evidence-based medicine is highly touted and used to denigrate or justify many treatments. But often the evidence is not there or is conflicting or flawed or tainted by private interest and politics.
Canada's CDEC clearly puts cost-effectiveness first. No doubt cash-strapped provinces prefer this.
Otherwise, why would the UK's NICE committee recommend funding Esbriet to treat IPF, and Canada's CDEC recommend the opposite, based on the same evidence?
For the record, NICE's 64-page report is transparent and discusses all issues in detail. CDEC's report is 5 pages.
UK experts noted that it was unlikely that clinical trials for IPF treatments can ever have enough statistical power to detect a difference in mortality. They recognized this limitation.
Yet new studies show Esbriet reduced the relative risk of death or disease progression by 43% compared with placebo.
Canada's experts chose to ignore statistical power.
Statistical power: Ability of a study to detect a real difference, if one exists. Power is affected by how big the difference is and sample size. If a difference is big, it's easier to detect. And large sample sizes make a real difference easier to detect.
5. Autopsies show that IPF coexists with many serious conditions, making diagnosis and treatment options difficult. As an example,
In discussing why spouse's lung biopsy showed evidence of pulmonary hemorrhage, not one specialist could explain it.
Seems medicine remains both a science and an art.
Miracle of miracles, early in Dec. 2014 we learned that the Alberta government would fund Esbriet under the STEDT program. For this we thank Peter's initial respirologist, Dr. Lyle Melenka. See
Expensive drug for deadly, rare lung disease funded by Alberta government (24 Dec. 2014)
As Peter and I deal with a diagnosis of an incurable disease, idiopathic pulmonary fibrosis, we focus on the glass half full. Every day, every month, every year is a blessing.
Which brings me to an old but fabulous Beach Boys ditty.
Good vibrations (Love this song)
Autopsies in acute exacerbation of idiopathic pulmonary fibrosis (Interesting findings. Perhaps they can be of use in treating IPF.)
Acute exacerbation in idiopathic pulmonary fibrosis.
Clear diagram of the 3 types of disease progression in IPF.
Drugs for rare diseases. Evolving trends in regulatory and health technology assessment perspectives (CADTH, Aug. 2013)
Quote in Summary on Alberta: 'A Short Term Exceptional Drug Therapy program for funding high-cost non-formulary drugs for rare conditions is available for both in-patients and outpatients.' [In theory, not in practice.]
As always, comment are welcome.
Labels: Alberta health, CADTH, Canadian Drug Expert Committee, Canadian Pulmonary Fibrosis Foundation, CDEC, Esbriet, idiopathic pulmonary fibrosis, interstitial lung disease, NICE, pirfenidone
Searching for a heart of gold (Musings on Alberta'...
Good vibrations (Musings on new research on idiopa...


text:
Armchair GM
Dany Heatley Buyout: A Study In Offseason Irrationality
By Mr. Plank Jun 7, 2011, 11:41am PDT
Share All sharing options for: Dany Heatley Buyout: A Study In Offseason Irrationality
For hockey fans slogging their way through the sleepy summer months, no website is trusted more than CapGeek.com. It is the go-to place for salary information, hypothetical roster building, and potential lineups. It is the Rosetta Stone when it comes to the common fan's attempt to understand the monetary side of the game.
Matthew Weust, who runs the website from his home in Nova Scotia, has accrued so many sources over the years that it has become commonplace for him to break signings before the MSM does. He's even been brought on to write for TSN during the high profile contract months (free agency and the trade deadline), offering his perspective on where a specific team stand in regards to their salary structure and ability to acquire talent.
Think of CapGeek as EA's NHL 2011 Be A GM Mode. Every conceivable roster at your fingertips, with buyouts, trades, free agents, and offer sheets all at your disposal. For some it's a tool to use for the greater good-- tweaks here and there to improve your favorite team, a trade here or there that makes sense for both clubs partaking in the festivities.
For others it's a highway to hedonism, as an analysis of the most popular buyouts over the last week will tell you.
The list of names here makes a lot of sense. Wojitek Wolski, Chris Drury, and Sean Avery all play for the New York Rangers-- with the Brad Richards sweepstakes in full swing since Dallas announced they would not re-sign him, the majority of Rangers fans are trying to find a way to break free of the shackles known as Glen Sather's contracts. Godspeed folks. Godspeed.
Sheldon Souray of the Edmonton Oilers is buried in minors and likely won't play in Edmonton ever again. Scott Gomez had a horrible season, posting 38 points and a -15 with three years left on a contract that pays him $7.3 MM per year. Komisarek, who has three years left at $4.5 MM per year, is a product of Toronto wanting to be active in the Free Agent market.
But wait, Dany Heatley? Former 50 goal scorer Dany Heatley of the San Jose Sharks, a player who finished fourth on the team in points this season, scored 39 goals in his first year with the team, and sees a healthy amount of time in the Sharks top six forward group?
Yes, that Dany Heatley. Buoyed by the fact that Heatley was largely ineffective for much of the Sharks 2011 postseason, posting three goals and six assists in eighteen games, the hounds have come out of the woodwork. Sporting a contract that has three years left and accounts for $7.5 MM of cap space per year, San Jose's ability to improve their blueline and shore up their penalty kill is slightly hampered by what some have called an albatross of a contract.
However, with Heatley on the books the Sharks still have a lot of flexibility heading into the offseason. At the very least they're looking at $10.175 MM in cap space to sign six skaters, four of which will be of the bottom line variety.
There's no doubt that Heatley has been a disappointment in the postseason during his two years with the Sharks. Brought in for his ability to score goals, Heatley has amassed a grand total of five in thirty two games played, an average of 12.8 when applied to an 82 game season. That production (or lack thereof) is what is fueling these buyout fires.
Further kindling is provided by the fact that Heatley's contract contains a No Movement Clause. The clause caused a deal sending him to the Edmonton Oilers in the summer of 2009 to be nullified after Heatley denied the trade, and makes moving him for the best return an unlikely possibility considering the organization would not be able to negotiate with all 29 potential trade partners.
But a buyout? Throwing in the towel that quickly despite the news that Heatley was playing with a broken left hand and a high-ankle injury during the 2011 postseason, dealt with a torn groin during the 2010 postseason, and underwent surgery this past offseason which caused rehabilitation issues during the entirety of this year?
It doesn't make any sense. For starters, this practice enact a cap hit against the team who engages in a buyout. According to CapGeek's buyout calculator, the San Jose Sharks would have a penalty of $1.6 MM next year, $3.6 MM in 12-13, $4.6 MM in 13-14, and $2.1 MM for the three years following. That is cap space being eaten up by a player who is not on the current roster-- in other words, you're allocating valuable salary resources to a player that is not helping you win hockey games.
Buyouts are used for players who have dropped off severely in talent level. They're for players who have no market value. They're not for your fourth highest scorer, and certainly not for a player who has fallen victim to injuries over the last two playoff runs.
Secondly, Heatley is still an effective player when he is healthy. While it's clear that his $7.5 MM contract is one that could shed a few unsightly pounds, he's a former 50 goal scorer who has a dangerous shot and has improved immensely on the defensive side of the ice. There is still immense value here, and even though his contract contains a No Movement Clause that would hamper San Jose's ability to get the best return for his services, there are numerous teams out there who would be willing to part with talent in order to acquire him.
Cap space is cap space. You use that cap space in order to acquire talented players. You don't shed cap space in order to acquire more cap space if it means your team would be worse off for it. Buying out Heatley would send tremors down the Sharks lines, pushing Pavelski up to the top six and leaving the bottom six forward group lacking a legitimate scoring threat. Coupled with the fact that the free agent class is a weak one, as well as the fact that San Jose has historically acquired players via trade, it sets up a situation where you would have to move more players (Pavelski, Setoguchi etc.) in order to capitalize on that cap space. Which would exponentially increase the issues of finding the ability to ice a competitive team.
The San Jose Sharks window of opportunity to win is right now. Dany Heatley, either through his play or in the unlikely event he is traded this offseason (which would bring in players that would help the team win), is going to be a big part of that.
A buyout makes little sense.
Which is unfortunately par for the course during the sleepy summer months that comprise the NHL offseason.