Abstract:
An endoscopic system comprises an endoscope having a fibreoptic cable bundle, an elongate insertion member for insertion into a patient and an operating port. Endoscopic tools, such as cytology brushes, may be inserted into the port. A piece of absorbent material is attached to a cytology brush which acts as a scaffold for the membrane allowing its controlled placement on internal body surfaces after it is inserted into the patient via the port and elongate insertion member. The material absorbs neat fluid from inside the patient. The cytology brush and SAM material are removed and the fluid extracted from the material. The SAM material is discarded, however the cytology brush may be reused on the same patient.

Description:
CROSS-REFERENCE TO RELATED APPLICATION 
       [0001]    This application is a national phase filing, under 35 U.S.C. §371(c), of International Application No. PCT/EP2010/063742, filed on Sep. 17, 2010, the disclosure of which is incorporated herein by reference in its entirety. 
     
    
     FIELD OF THE INVENTION 
       [0002]    This invention relates to an endoscopic system and particularly, although not exclusively, to a bronchoscopic system. 
       BACKGROUND 
       [0003]    Endoscopy is widely used as a diagnostic and clinical monitoring method for the visual inspection of the interior of the body, allowing tissue, cells and fluid samples to be removed for testing, as well as for minimally invasive surgery. An endoscope generally comprises a tube for insertion into a body cavity or small incision. The tube contains an optical system that conveys light from a light source into the body cavity and returns light to allow a practitioner to observe the interior of the cavity. A camera may be fitted to the tube. The optical system may be in the form of a fibre optic system, allowing the tube to be flexible. The tube may include a longitudinal passageway (or catheter insertion channel) to allow insertion of tools such as probes, brushes or like instruments into the cavity from the exterior of the patient. 
       SUMMARY OF THE INVENTION 
       [0004]    Bronchoscopy is a procedure which utilises a specific endoscope designed for insertion into the lung. There are several existing sampling techniques which attempt to detect robust biomarkers, seek accurate phenotyping of respiratory diseases and which can potentially track inflammatory changes in response to disease activity. Bronchoscopy is routinely performed on patients with respiratory disease in order to carry out bronchoalveolar lavage (BAL), endobronchial mucosal biopsy and brushings. BAL is the most common way in which to sample the components of the epithelial lining fluid (ELF) and to determine the inflammatory mediator composition of the pulmonary airways, and it is often used in immunological research as a means of sampling cells or pathogen levels in the lung. The procedure involves advancing a bronchoscope until it is wedged in a subsegmental bronchus at the desired location within the lung. Approximately 20 mL of saline is injected with a syringe via an operating port and longitudinal passageway of the bronchoscope. The flow of saline from the distal end of the bronchoscope is observed via the bronchoscope&#39;s optical system. Maintaining the wedge position, gentle suction is applied, collecting the lavage specimen in a collection trap, but at a high and unknown dilution. This process is repeated up to 5 times (with a total amount of introduced slaine of 100-120 mL) as needed to obtain an adequate specimen of about 40-60 mL. There is usually a 40-70% recovery of total instillate. 
         [0005]    The unknown dilution and range in the volume of fluid retrieved can make the accurate evaluation of the severity or progress of a disease difficult and many sensitive markers of inflammation may remain below the limits of detection. 
         [0006]    Another major clinical limitation for the utility of examining bronchoalveolar lavage fluid (BALf) is the large range of normal values for each parameter, which makes BALf insensitive in detecting disease. Furthermore, abnormalities in BALf are rarely specific for any of the lung diseases. There are some patients who have normal BALf constituents despite a definite disease and some without any evidence of disease despite abnormal BALf findings. There is large interindividual variation which may not be related to the disease, and the airspace cells and secretions may not reflect interstitial processes. Also, the removal of BALf may preferentially select, activate or injure some cells, and the composition of the epithelial lining fluid may change during the bronchoalveolar lavage. 
         [0007]    Mucosal biopsy involves the removal of inner lung tissue fragments and bronchial brushing similarly involves the removal of endobronchial superficial cells. However, none of the existing techniques allow for accurate measurement of inflammatory mediators and biomarkers present in the lining fluid of the lung. Biomarkers and inflammatory mediators in the ELF reflect inflammation in the underlying tissue; hence it is important that they are accurately quantified. 
         [0008]    Existing bronchoscopic procedures can have adverse effects including bleeding, infection or a reactive pyrexia. 
         [0009]    According to the present invention there is provided an endoscopic system comprising: an elongate member for insertion into a body, the elongate member having a longitudinal passage; an elongate tool for insertion into the longitudinal passage; and a piece of absorbent material for attaching to the elongate tool for collecting a sample from inside the body and for subsequently removing the sample. 
         [0010]    Such an endoscopic system allows undiluted and uncontaminated fluid to be removed from the body. The system is simple to construct and can be operated without any significant extra training by a physician with experience of endoscopy. The endoscopic system may include a bronchoscope. The operation of this bronchoscopic system can be performed during a routine bronchoscopy. 
         [0011]    Preferably the piece of absorbent material is an absorptive matrix material having a high wicking rate and a high absorptive capacity such as a fibrous hydoxylated polyester absorptive matrix material. Such a material is less likely to cause damage, bleeding or other adverse effects within the body than existing techniques and can quickly obtain a sample of high volume. 
         [0012]    According to the present invention there is provided a method of operating an endoscopic system comprising: inserting an elongate member into a body, the elongate member having a longitudinal passage; attaching a piece of absorbent material to an elongate tool; inserting the elongate tool into the longitudinal passage; and collecting a sample from inside the body with the absorbent material and subsequently removing the sample. 
         [0013]    The endoscopic system may be a bronchoscopic system which allows other established and routine bronchoscopic procedures to be performed as normal following the inventive sampling method. The sample recovered can comprise undiluted lining fluids which will have improved signal to noise ratios and increased amounts of detectable inflammatory mediators compared with existing methods. 
         [0014]    The invention also provides an absorbent sheet material for taking a sample of bodily fluid, the sheet material adapted to be configured into a structure suitable for attaching to an elongate tool for insertion into an endoscope. Preferably the sheet material is configured into a tubular structure such as a cylinder and held in this form by inert biomedical adhesive. It is suitable to supply such a sheet material separately from the other components of the system and in an individual, sterile packaging. The material is quick and easy to attach to the elongate tool and is a single use item which is discarded after use. 
         [0015]    Preferably the absorbent sheet material will release the absorbed sample when subjected to a centrifuge process. Thus the material does not require any washing to extract the collected sample and neat secretions can be obtained. 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         [0016]    Embodiments of the present invention will now be described, by way of example only, with reference to the accompanying drawings in which: 
           [0017]      FIG. 1  illustrates an endoscope suitable for use in the present invention; 
           [0018]      FIG. 2  illustrates a cytology brush suitable for use in the present invention; 
           [0019]      FIG. 3  is a plan view of a piece of absorbent material with two strips of biomedical adhesive; 
           [0020]      FIG. 4  illustrates the absorbent material of  FIG. 3  formed into a cylinder; 
           [0021]      FIG. 5A  illustrates the absorbent material of  FIGS. 3 and 4  attached to the cytology brush of  FIG. 2 ; 
           [0022]      FIG. 5B  illustrates the absorbent material and brush arrangement of  FIG. 5A  housed inside a guide sheath of the cytology brush. 
           [0023]      FIG. 5C  illustrates the absorbent material and brush arrangement deployed from e guide sheath. 
           [0024]      FIG. 6  is a flow chart describing the method of operation of an endoscopic system of the present invention. 
       
    
    
     DETAILED DESCRIPTION 
       [0025]    Referring firstly to  FIG. 1 , an endoscope  1  is illustrated comprising a housing  2  and an elongate insertion member  3  extending from the housing  2  and having a distal end  4  illustrated in a schematic, enlarged view  5 . The insertion member  3  comprises a fibre optic cable bundle  6  that extends the length of the cord to allow the user to observe a field of view at the distal end  4  for example within a body cavity, a conduit that acts as light source  7  for the field of view under observation and an exit aperture  8 ′ of a channel  8  which extends longitudinally through the insertion member  3 . The endoscope further comprises an eyepiece  9  located at the opposite end of the housing  2  from the insertion member  3  to allow the user to observe the fled of view at the distal end of the insertion member  3  through the fibre optic bundle  6 . The housing  2  also has an associated control mechanism  10 , input/output cable  11 , an insertion channel port  12  and a suction channel port  13 . 
         [0026]    The insertion member  3  may be flexible or rigid or may have both rigid and flexible portions. The length of the insertion member  3  may be anything from a few centimetres to over 230 centimetres depending on the intended use. 
         [0027]    The insertion channel port  12  is used for introducing and withdrawing sampling devices and fluid and for the introduction of medication. The channel  8  extends longitudinally through the insertion member  3  from the insertion channel port  12  to the exit aperture  8 ′. This channel branches inside the housing  2  such that it is also connected to the suction channel port  13 . The suction channel port is configured to have a suction device attached to it and is used for removing fluid. The fibre optic cable bundle  6  extends between the distal end  4  of the insertion member  3  and the eyepiece  9 . The light source conduit  7  is fed with light from an external source (not shown) through the input/output cable  11  The fibre optic cable bundle  6  transmits an image from the distal end  4  to the eyepiece  9 , where it may be viewed by an operator of the endoscope  1 . The image may also be output to a screen, recording unit or transmission means (not shown) through the input/output cable  11 . 
         [0028]    The control mechanism  10  allows the distal end portion  4  of the insertion member  3  to be dynamically bent and rotated. This is achieved via a system of longitudinally running Bowden cables that extend from within the member  3  near the distal end  4  to levers within the housing  2 , forming part of the control mechanism  10 . The flexible distal end of the member  3  allows the operator of the endoscope  1  to navigate the instrument and to change the view direction within a body cavity. 
         [0029]    As well as providing the light source and an output for the fibre optic cable bundle  6 . the input/output cable  11  may also provide electrical power to any other components of the endoscope requiring such power. 
         [0030]    A tool which is often used during endoscopic procedures is a cytology brush and an example is shown in  FIG. 2 . The cytology brush  14  has a handle  15  comprising a grip portion  16 , a ring portion  17  and a flexible elongate portion  18 . The flexible elongate portion  18  is generally constructed of an inner wire  19  slidably received with a sheath  20  of plastics material. A brush portion  21  is located at the distal end of the cytology brush. The diameter of the inner wire  19  portion is 1 mm and the brush portion  21  diameter ranges from 1.2 mm to 5 mm depending on the intended use. 
         [0031]    The ring portion  17  of the handle  15  is moveable with respect to the grip portion  16 . When the ring portion  17  is pulled, it moves away from the grip portion  16  and causes the inner wire  19  to move within the sheath  20 . This action causes the brush portion  21  to be retracted into the plastic sheath  20  of the flexible elongate portion  18 . When the ring portion  17  is pushed back towards the grip portion  16 , the brush portion  21  protrudes from the sheath  20 . 
         [0032]    The cytology brush  14  is designed to be inserted into the endoscope  1  through the insertion channel port  12  for example to perform a brushing within the lung to take a sample. The ability to retract and deploy the brush portion  21  facilitates the protection of any sample the brush has collected from contamination as the cytology brush  14  is withdrawn from the endoscope  1 . 
         [0033]    Preferably the sheath  20  has a 2.6 mm inner diameter channel and the endoscope insertion channel has an inner diameter of 2.8 mm. 
         [0034]      FIGS. 3 and 4  illustrate a piece of absorbent sheet material  22  such as an analytical membrane for use in the present invention. The material  22  is configured to be attached to or scaffolded over an endoscopic tool such as the cytology brush of  FIG. 2 . The piece of material  22  may be of any dimensions suitable for attachment to an endoscope tool. The piece may, for example, be approximately 7 mm wide and 50 mm long. 
         [0035]    The material  22  may be any substance suitable for benign introduction into the human body and for absorbing fluid. The material  22  may be constructed from a number of quality controlled base materials, for example, graded 100% cellulose fibre, cellulose and rayon blend, borosilicate glass fiber with PVA binder, cellulose and synthetic blend with PVA binder or a fibrous hydoxylated polyester. The material  22  may be provided in various thicknesses, absorbencies and wick rates to meet the specific sampling needs. The piece of absorbent material  22  may preferably have a fast wicking rate (&lt;20 s/3 cm) and a high absorption capacity (&gt;100 μL/cm 2 ) to allow for rapid absorption of a high volume of bronchial epithelial lining fluid. 
         [0036]    An example of a material suitable for use in the present invention is “Accuwick Ultra”, manufactured by Pall Corporation (Europa House, Havant Street, Portsmouth, Hampshire, PO1 3PD). The material may be provided in a pre-sized, individual form as shown in  FIG. 3  by Parafix Tapes &amp; Conversions Ltd (Spencer Road, Lancing Business Park, Lancing, West Sussex. BN15 8UA). Alternatively, the material may be provided as several units which require manual detachment or may come as a roll of many units. The material may be further sterilised with gamma radiation after being attached to an endoscope tool. The individual material pieces may come in a sterile packaging for opening immediately prior to use. 
         [0037]    The piece of absorbent material  22  may have an absorbent sink (not shown) located at one end of the material  22 . This sink acts as a reservoir for the fluid sample after it has travelled through the material via a wicking process. The absorbent sink is typically constructed of either glass fibre or cellulose materials and helps to control the flow rate of fluid into the absorbent material  22 . The absorbent sink preferably has the same thickness as the absorbent material  22 , and is provided pre-fabricated with the absorbent material  22 . 
         [0038]    The absorbent material  22  has strips  23  of adhesive, for example a double sided inert sticking tape as manufactured by Parafix Tapes &amp; Conversions Ltd. The adhesive may alternatively be an inert biomedical glue. The strips  23  of adhesive do not contain a residual solvent and are safe for introduction into the human body. The adhesive may be applied by a technician or physician after removing the material  22  from any packaging or may be pre-applied prior to any packaging of the material  22 . The adhesive strips  23  may have a peel-off covering to prevent the strips sticking to any packaging. The adhesive substance may be arranged in one or more longitudinal strips  23  which may extend the entire length of the absorbent material  22 , or over only a portion of its length. The adhesive substance may alternatively be arranged in one or more curved strips or in patches and may be located along one or both sides of the piece of absorbent material  14 . Tests with the Accuwick Ultra absorptive matrix material have shown that a piece of the material of dimensions 7 mm by 50 mm can absorb in excess of 250 μl of fluid. 
         [0039]      FIG. 4  shows the piece of absorbent sheet material  22  of  FIG. 3  formed into a cylinder. The material is preferably formed into a cylinder manually by a medical technician or a physician. The dashed line illustrates the edge position of the side of the absorbent material  22  which does not include the adhesive strips  23  and which may be hidden from view when the cylinder is formed. 
         [0040]    The absorbent material  22  is preferably formed into a cylinder around the brush portion  21  of the cytology brush as shown in  FIG. 5A . The cylinder of absorbent material is affixed to the brush portion  21  by the friction between the bristles  24  and the inner surface of the cylinder. By forming the cylinder around the brush  21 , a secure fit and strong attachment is provided. Preliminary tests have shown that a friction based attachment is sufficient to prevent detachment of the absorbent material  22  during an endoscopic procedure. However should the material become detached, it can be removed by endoscopic forceps. 
         [0041]      FIG. 5B  shows the absorbent material  22  formed into a cylinder around the brush portion  21 , the brush portion  21  being located inside the sheath  20  of the elongate portion  18  of cytology brush  14 . While in this position the elongate portion  18  of the cytology brush  14  is inserted into the endoscope  1  via the insertion channel port  12  without damaging the brush head or the affixed absorbent material  22  or dislodging the absorbent material  22 . 
         [0042]      FIG. 5C  shows the brush portion  21  of the cytology brush  14  and affixed absorbent material  22  after being deployed from the sheath  20 . While in this position the absorbent material  22  is able to collect a sample. The brush portion  21  is withdrawn into the sheath  20  in order to withdraw the cytology brush  14  from the endoscope  1 . 
         [0043]    A preferred method of operating the endoscopic system will now be described with reference to  FIG. 6 . In step S 1  the absorbent material  22  is formed into a cylinder as shown in  FIG. 4  and in step S 2  the cylinder of absorbent material is attached to the cytology brush  14 . In practice these two steps may be performed simultaneously, with the absorbent material being fashioned around the brush portion  21  so that a secure fit results. In order to allow steps S 1  and S 2  to be performed, the brush portion  21  of cytology brush  14  is deployed from the sheath  20  by pushing the ring portion  17  of the handle  15  towards the grip portion  16 . This exposes the brush portion  21  and allows the absorbent material  22  to be easily attached. Once the absorbent material  22  is attached to the brush portion  21 , the brush portion  21  is retracted into the sheath  20 . 
         [0044]    At step S 3  the insertion member  3  of the endoscope  1  is inserted into a body cavity. In bronschoscopy the elongate member is inserted through the nasal or oral cavity and down the trachea into the lung. 
         [0045]    Once the endoscope has been inserted, the cytology brush  14  is inserted into the insertion channel port  12  at step S 4 . During insertion, the brush portion  21  remains inside the sheath  20  of the flexible elongate portion  18  so as not to cause contamination of the absorbent material. 
         [0046]    The brush portion  21  with the absorbent material  22  attached is then deployed from the sheath  20  at step S 5 . This is achieved by the operator of the endoscope  1  pushing the ring portion  17  of the handle  15  towards the grip portion  16 , causing the inner wire  19  to move within the sheath  20 . The brush portion  21  need not necessarily be fully extended from the sheath  20 , and some of the length of the absorbent material  22  may remain inside the sheath  20 . The deployment of the brush portion  21  is observed by the endoscope operator through the eyepiece  9  or on a screen which the image is output to through the input/output cable  11 . This allows the operator to carefully select the place within the body to which the brush portion  21  will be deployed and from which the absorbent material  22  will collect a sample. Such control is important to reduce the chance of the brush portion  21  causing damage. 
         [0047]    A sample of fluid is absorbed by the absorbent material  22  at step S 6 . This is achieved by the absorbent material  22  coming into contact with an inner surface of the body cavity. The absorbent material  22  may typically be deployed for approximately 60 seconds. 
         [0048]    Once a sample has been successfully collected, the brush portion  21  is retracted into the sheath  20  at step S 7 . This is achieved by the operator of the endoscope  1  pulling the ring portion  17  of the handle  15  away from the grip portion  16 , causing the inner wire  19  to move within the sheath  20 . This ensures that the absorbent material  22  does not become dislodged from the brush portion  21  as the brush is withdrawn and also prevents contamination of the sample. The cytology brush  14  may have a relatively large sheath of 2.6 mm inner diameter. This allows the absorbent material  22  to be easily accommodated within the sheath  20 . The absorbent material  22  becomes engorged when it absorbs a sample of fluid and the large diameter sheath  20  ensures that the absorbent material  22  can be easily retracted while retaining a sample. 
         [0049]    The cytology brush  14  is removed from the endoscope  1  at step S 8 . During this step the insertion member  3  of the endoscope  1  remains inside the body cavity. The endoscope operator pulls on the handle portion  15  of the cytology brush  14  to slide the elongate portion  18  out of the insertion channel of the endoscope  1 . 
         [0050]    At step S 9  the absorbent material  22  is detached from the brush portion  21 . In order to perform tests on the fluid sample, it is extracted from the absorbent material  22 ; this may be achieved by centrifuge. 
         [0051]    At step S 10  the absorbent material  22  is placed in a suitable container, such as an Eppendorf tube and then placed in a spin filter. Centrifugation is performed to obtain the neat fluid. The absorbent material  22  is preferably low protein binding in nature, allowing for an easy recovery of the protein mediators by centrifugation. Thus the absorbent material  22  does not require any elution or washing to extract the collected neat samples. The sample is therefore obtained in an undiluted form. 
         [0052]    The absorbent material may be weighed at a time before step S 1  and again after step S 9 . The increase in weight can then be compared with the volume of fluid collected. The piece of absorbent sheet material  22  is a single use item and should be discarded in a safe manner after use. The cytology brush may be used again during the same endoscopic procedure to collect cell samples; it is then discarded. 
         [0053]    Preferably the method of the invention relates to a bronchoscope and bronchoscopic procedure. This method may be the sole procedure or may be performed in combination with other bronchoscopic procedures. Preferably the method described is the first procedure to be performed as it does not affect in any way the subsequent implementation of routine bronchoscopic procedures, such as endobronchial washing, brushing and biopsy. The undiluted fluid which is collected may be analysed using existing techniques to detect biomarkers. The neat samples obtained by this method may have greater than 10 times the level of detectable inflammatory mediators than samples obtained with existing procedures. 
         [0054]    While the invention has been described with reference to a specific embodiment, variations be apparent to the person skilled in the art and these variations are intended to fall within the scope of the appended claims. For example, although the endoscopic system of the present invention has been described in terms of a bronchoscopic system, the invention may also be applied to thoroscopy, laparoscopy, nasendoscopy, colonoscopy, gastroscopy, cystoscopy and arthroscopy.