WO2018087563A1

WO2018087563A1 - Cryoablation

Info

Publication number: WO2018087563A1
Application number: PCT/GB2017/053399
Authority: WO
Inventors: Brian Clarke
Original assignee: Nitro Medical Limited
Priority date: 2016-11-14
Filing date: 2017-11-10
Publication date: 2018-05-17

Abstract

A cryoablation apparatus (100) comprising a primary liquid cryogen chamber (101), a secondary liquid cryogen chamber (102) in selective or free communication with the primary cryogen chamber (101), an endoscopic cryoablation catheter (103) and a vacuum source (104), the endoscopic cryoablation catheter (103) having a first end (103A) and a second end (103B), a cryoablation zone 108 being provided at the second end (103B), an umbilical (105) extending between the first end (103A) and the second end (103B), wherein the secondary liquid cryogen chamber (102) is located at, adjacent or proximate the first end (103A) and, in use, the vacuum source (104) is configured to draw cryogenic vapour from the secondary liquid cryogen chamber (102) along the umbilical (105) to the second end (103B) to cool the cryoablation zone (108) and thence along the umbilical (105) towards the first end 103A.

Description

Cryoablation

This invention relates to cryoablation, specifically the cryoablation of unwanted tissue such as tumours (benign or malignant) and to the apparatus for conducting cryoablation.

Pancreatic cancer is one of the major causes of cancer-related mortality in the world. Long- term survival is dismal with approximately less than 5% of patients alive 5 years after diagnosis. Radical surgical resection represents the main viable opportunity for cure but unfortunately the procedure is only available to less than 25% of patients due to vascular invasion, poor general health or the lack of surgical support. In most of those cases the standard therapy is chemotherapy followed by radiation therapy. The survival rate is typically less than a year. Indeed most patients present with unresectable pancreatic cancer and 40-45% of those patients have metastatic disease, mainly hepatic, which carries a median survival of 3 to 6 months.

Techniques for the treatment of unresectable pancreatic cancer include cryotherapy (CT) and radiofrequency ablation (RFA) with cryosurgery being preferred because of the difficulty in assessing the ablated zone by ultrasound when deploying RFA techniques.

The standard procedure for cryosurgery is performed intraoperatively or percutaneously.

In the former case the patient is anaesthetized and the pancreas exposed by transperitoneal immobilization of the bowel and stomach. When it is determined that the tumour is unresectable cryosurgery is performed in direct vision and under the guidance of ultrasound. A variable number (usually 1 to 3) of fine (e.g. 1 .4 - 1.7 mm) cryoprobes are placed directly into the pancreatic mass and a double cycle of the freeze-thaw procedure is undertaken. In the case of percutaneous cryosurgery, the patient is positioned so that the entire tumour is visible using ultrasound through the abdomen or back and cryoprobes are inserted percutaneously. The probe entry site is determined by ultrasound and is effected transabdominal^ through the stomach or the left lobe of the liver or transdorsally between T12 and L7 about 5cm from the spine. A cryoprobe is advanced to the centre of the tumour mass under real-time ultrasound guidance until the probe is located along its distal inner border. For tumours larger than 3 cm, 2 to 4 cryoprobes (1.7mm diameter) are used. Again a double freeze-thaw cycle is performed.

In both cases, postoperatively the patient is admitted to intensive care for monitoring with a median hospital stay of about 20 days. Whilst there have been no reported deaths from the effects of pancreatic cryoablation the prognosis for patients is not promising with one study showing a median survival time of 8.4 months with the survivability rate at 12 months being 43.2% for those patients without liver metastases and 13.7% for those with liver metastases (Nui et a/.; World Conference on Interventional Oncology (2010); Philadelphia USA; pp27).

It is postulated that one of the reasons for the low survivability rate may be that postoperatively it is not possible to commence chemotherapy and/or radiotherapy due to the surgical procedures deployed. Whilst it has been suggested that cryoablated cancerous tissue has an increased sensitivity to chemo/radiotherapy [Gage et al; Cryobiology, 59, pp 229 -243] it is not possible to commence chemotherapy until the surgical wounds and the patient have sufficiently recovered. In the circumstances of intraoperative or percutaneous cryoablation the surgical recovery may take 2 to 3 weeks which represents a window for remaining, mobile or nascent cancer cells to metastasize. Accordingly, there is a need for surgical procedures and equipment which can significantly reduce postoperative recovery time to enable conventional therapies to be deployed sooner after cryoablation.

Endoscopic cryoablation catheters are known. For example, US2014275767 A1 describes a cryoablation catheter for use in the ablation of unwanted tissue in the treatment of pancreatic cancer. The method of cooling the ablation zone of the catheter is not described.

Cryoablation catheters, particularly endoscopic cryoablation catheters, are advantageous because these can be inserted into the body to reach the site of use, without the need for abdominal incision.

Catheters for cryoablation are distinct from probes for cryoablation in that probes are generally rigid, comprising rigid handles and/or bodies, and generally comprise a probe tip with a larger diameter than the tip of a catheter (say, greater than 1.4 or 1.7 mm, and preferably greater than 4mm). Their size and rigidity means that open, or laparoscopic, surgery is required. This precludes their use in procedures, e.g. endoscopic procedures, which do not require abdominal incision. In contrast, catheters for cryoablation are generally flexible, and may comprise a relatively smaller diameter at the tip of the catheter (say, less than 2mm). Advantageously, this enables their use in procedures such as endoscopies, which reduces postoperative recovery time because no incision has been made in the patient.

A first aspect of the invention provides a cryoablation apparatus comprising a primary liquid cryogen chamber, a secondary liquid cryogen chamber in selective or free communication with the primary cryogen chamber, an endoscopic cryoablation catheter and a vacuum source, the endoscopic cryoablation catheter having a first end and a second end, a cryoablation zone being provided at the second end, an umbilical extending between the first end and the second end, wherein the secondary liquid cryogen chamber is located at, adjacent or proximate the first end and in use, the vacuum source is configured to draw cryogenic vapour from the secondary liquid cryogen chamber along the umbilical to the second end to cool the cryoablation zone and thence along the umbilical towards the first end.

The apparatus may comprise a throttle, e.g. for controlling, in use, the flow of cryogenic vapour drawn from the secondary liquid cryogen chamber along the umbilical to the second end of the endoscopic cryoablation catheter. The throttle may be adjustable and/or may comprise a valve means.

The vacuum source may be connected to or in communication with the endoscopic cryoablation catheter, for example by or via an exhaust line.

The endoscopic cryoablation catheter may be between 1 to 6 meters in length, e.g. 1 to 4 meters, say 1 to 2 meters in length. The endoscopic cryoablation catheter may comprise a handle. The distance between the midpoint of the handle and the first end may be between 1 to 4 meters, e.g. between 1 to 2 meters, say 1 meter. The handle may have a length of between 10 to 20 cm, e.g. 15cm.

The endoscopic cryoablation catheter may comprise a needle tip at its second end. The umbilical may comprise a tri-axial line, e.g. comprising a delivery conduit, an exhaust conduit and an insulating conduit. The delivery conduit, exhaust conduit and insulating conduit may be concentric. The delivery conduit, exhaust conduit and/or insulating conduit may comprise one or more spacing members therewithin.

The endoscopic cryoablation catheter may have a diameter at its second end of between 1 and 5mm, preferably of between 1 and 3mm.

The secondary liquid cryogen chamber may comprise a heater or heating element or a dispersive medium, e.g. configured to aid with boiling of liquid cryogen.

A further aspect of the invention provides a method of cooling the end of an endoscopic catheter to cryoablation temperatures, the method comprising providing a chamber containing a liquid cryogen at, adjacent or proximate a first end of an endoscopic catheter, the endoscopic catheter having a second end providing a cryoablation zone and an umbilical extending between the first end and the second end, and using a low pressure to draw cryogenic vapour from the chamber along the umbilical to the second end to cool the cryoablation zone and thence from the second end towards the first end. The method may comprise boiling a portion of the liquid cryogen contained in the chamber into cryogenic vapour.

The method may comprise supplying liquid cryogen from a further chamber to the chamber. The method may comprise drawing cryogenic vapour under the influence of negative pressure provided by a vacuum source.

As will be appreciated, endoscopic catheters need to be thin and flexible to allow them to be located at the desired site of use within the body. To date, cryoablation catheters have relied, principally, on effecting cryoablation using the Joule-Thomson (JT) effect whereby a high-pressure gas (for example N2O, CO2, Ar, He) is forced through a throttle to expand adiabatically and thereby cool. In thin conduits high pressure gas is obviously a concern because failure of the conduit may lead to leakage of the high pressure gas into the body, which clearly would be dangerous. Moreover, because endoscopic catheters may be long (the umbilical may be long to enable to the catheter to arrive at the desired site) and thin the pressures required to force the gas along the catheter can be considerable.

An alternative to deploying the JT effect in cryosurgery is to use liquid nitrogen as the cryogen. However, forcing liquid nitrogen along a thin and long conduit which would be required for an endoscopic catheter is difficult due to the frictional losses experienced by the liquid as it traverses the conduit. We have found that using suction to draw cryogenic vapour along the umbilical successfully mitigates the above issues. A yet further aspect of the invention provides a method of treating a tumour, the method comprises inserting a catheter endoscopically into a patient and guiding it to a site of use, locating the end of the catheter in the tumour, utilising a source of low pressure to draw cryogenic vapour from an upstream store of liquid cryogen through and along the catheter to the end of the catheter, thereby to cool the end of the catheter and cryogenically treat the tumour, and thence back along the catheter in an exhaust conduit.

Because the catheter is inserted endoscopically there is no trauma to the abdomen of the patient. This means that postoperative recovery can be significantly shorter than for conventional surgical interventions when, for example, treating pancreatic cancer.

We have found that using cryogenic vapour it is easily possible to generate the required cooling capacity at the cryoablation zone to effect cryoablation of tissue, specifically tumour tissue. As will be appreciated, the cooling capacity (Q/kW) is the capacity to remove heat from a system and is proportional to the mass rate of refrigerant (m/kgs^"1) and the change in temperature (ΔΤ/Κ). We prefer to use a cryogen vapour, preferably comprising cryogen gas (e.g. nitrogen) in which is suspended small particles or globules of cryogenic liquid (e.g. liquid nitrogen).

In order that the invention may be more fully understood, it will now be described, by way of example only, and with reference to the accompanying drawings, in which:

Figure 1 is a schematic view of a cryoablation apparatus according to the invention;

Figure 2A is a cross-sectional view of a part of a catheter of the apparatus of Figure 1 ; Figure 2B is a perspective view of the catheter along the line 105A;

Figure 2C is a cross-sectional view of a further part of the catheter in Figure 2A; Figures 3A and 3B are cross-sectional views of a second embodiment of a cryoablation catheter of invention;

Figures 4A and 4B are cross-sectional views of a third embodiment of a catheter for use with the invention; and

Figure 5 is a schematic view of the secondary liquid cryogen chamber and a portion of the delivery line of the apparatus of Figure 1.

Referring first to Figure 1 there is shown a cryoablation apparatus 100 which comprises a primary liquid cryogen chamber 101 , a secondary liquid cryogen chamber 102, an endoscopic cryoablation catheter 103, and a vacuum source 104. The endoscopic cryoablation catheter 103 comprises a first proximal end 103A, a second distal end 103B, an umbilical 105, a needle tip 106 and a handle 107. The umbilical 105 extends between the first end 103A and the second end 103B of the endoscopic cryoablation catheter 103. It should be noted that the umbilical 105 is not drawn to scale. The length (not shown) of the umbilical 105 is schematically represented with 'breaks'. The umbilical 105 is continuously connected from the first end 103A to the second end 103B. The handle 107 may be located at or towards the middle of the umbilical 105. A cryoablation zone 108 is provided at the second end 103B, in the region of the needle tip 106, the end of which terminates at the second end 103B of the endoscopic cryoablation catheter 103. The secondary liquid cryogen chamber 102 is located at, adjacent or proximate the first end 103A of the endoscopic cryoablation catheter 103. The secondary liquid cryogen chamber 102 is connected to the umbilical 104 by means of a connector 109. The endoscopic cryoablation catheter 103 is connected to, or in communication with, the vacuum source 104 by, or via, an exhaust line 1 10.

The primary cryogen chamber 101 is connected to the secondary liquid cryogen chamber 102 by a delivery line 111. The secondary liquid cryogen chamber 102 is in selective or free communication with the primary liquid cryogen chamber 101. By selective communication, we mean that the connection between the secondary liquid cryogen chamber 102 and the primary liquid cryogen chamber 101 may comprise means to control the flow of liquid cryogen between the primary liquid cryogen chamber 101 and the secondary liquid cryogen chamber 102. For example, these may be provided by a valve or stopcock to control and partially or completely arrest the flow of liquid cryogen from the primary liquid cryogen chamber 101 to the secondary liquid cryogen chamber 102. By free communication we mean that, in use, liquid cryogen is able to flow freely from the primary liquid cryogen chamber 101 to the secondary liquid cryogen chamber 102 as the cryogen is spent during operation of the cryoablation apparatus 100.

The apparatus for the supply of liquid cryogen and the vacuum source 104 may be located within a common housing.

The endoscopic cryoablation catheter 103 may be between 1 to 6 metres in length, e.g. 1 to 4 metres, or say 1 to 2 metres in length. The distance from the connector 109, at the first end 103A, to the mid-point of the handle 107 may be between 1 to 4 metres, e.g. between 1 to 2 metres or 1 metre. The length of the handle may be 10 to 20 cm, e.g. 15 cm. The distance between the mid-point of the handle 107 and the needle tip 106, at the second end 103B, is between 0.5 to 2 metres, e.g. between 0.5 to 1.5 metres, or say 1 metre.

Referring now to Figure 2A there is shown a cross-sectional view of the second end 103B of the endoscopic cryoablation catheter 103. The second end 103B comprises the umbilical 105, the cryoablation zone 108, the needle tip 106, and a sheath 1 12. In this embodiment, the umbilical 105 is a tri-axial line comprising a delivery conduit 113, an exhaust conduit 1 14, and an insulating conduit 1 15, which are concentric. The exhaust conduit 1 14 may contain spacers 116, and the insulating conduit 1 15 may also contain spacers 1 19.

The cryoablation zone 108, which begins at the needle tip 106, is preferably 10 to 15mm in length and extends circumferentially around the umbilical 105. The diameter of the endoscopic cryoablation catheter 103 at the second end 103B is between 1 mm and 5mm, preferably between 1 mm and 3mm.

Referring now to Figure 2B there is shown a cross-sectional view of the tri-axial umbilical 105, along the line 105A of Figure 2A. The delivery conduit 1 13 is located within the exhaust conduit 114, which in turn is located within the insulating conduit 1 15. In the cryoablation apparatus 100, the delivery conduit 1 13 is connected to the connector 109, and is in free communication with the secondary liquid cryogen chamber 102. The exhaust conduit 114 is connected to the exhaust line 1 10 and is in free communication with the vacuum source 104. In use, cryogenic vapour is drawn along the delivery conduit 113 towards the needle tip 106 to cool the cryoablation zone 108, after which the spent cryogenic vapour is drawn along the exhaust conduit 1 14 toward the first end 103A under vacuum. The direction of flow of cryogenic vapour is indicated with the arrows 117 in the delivery conduit 113 and the arrows 1 18 in the exhaust conduit 1 14.

The exhaust conduit 114 may contain spacers 116, which support the walls of the conduit to prevent collapse when the cryoablation apparatus 100 is in use. The spacers 1 16 may be provided along the entire length of the exhaust line 114, and may be any shape so long as the passage of cryogenic fluid is not occluded. The spacers 116 are thermally insulating and may be fabricated from glass, ceramics, plastics or other materials resistant to damage from thermal cycling and cleaning regimes.

The insulating conduit 1 15 may also contain spacers 119. The spacers 119 in the insulating conduit 1 15 may be made of an insulating material such as glass or ceramic, or may be printed onto inner surface 115A of the insulating conduit 1 15. The spacers 119 may be present along the entire length of the insulating conduit 115. The spacers 119 act to support the walls of the conduit and prevent collapse of the insulating conduit 1 15, and also prevent the exhaust conduit 1 14 from contacting the insulating conduit 115. In this way, the efficiency of the cryoablation apparatus 100 is increased.

The sheath 1 12 is provided on a portion of the umbilical 105. The sheath 1 12 extends circumferentially around the outer surface of umbilical 105, and longitudinally extends from the handle 107 along the umbilical 105 towards the needle tip 106, terminating approximately 1 to 20mm from the cryoablation zone 108.

The sheath 112 encases the insulating conduit 1 15, which provides a region of insulation to the endoscopic cryoablation catheter 103. Advantageously, the sheath 1 12 and the insulating conduit 1 15 prevent injury to the surrounding tissue not intended to be contacted with parts of the cryogenic temperatures. The sheath 1 12 and the insulating conduit 115 also provide insulation along the endoscopic path.

The umbilical 105 and the sheath 1 12 are composed of a flexible material, for example, a polymeric material. Advantageously, the umbilical 105 and the sheath 1 12 may be fabricated from a suitable material to allow for easy sterilisation. Sterilisation is generally accomplished by autoclaving, which typically deploys a high pressure and/or high temperature steam treatment. The sheath 112 may be removable or alternatively made from materials resistant to cleaning products in chemical sterilisation. Advantageously, this allows for multiple uses of the endoscopic cryoablation catheter 103.

The delivery conduit 113, the exhaust conduit 114, and the insulating conduit 1 15 are composed of material that is rigid but flexible. For example, the delivery conduit 1 13 may be composed of stainless steel, and the exhaust conduit 1 14 may be composed of polyamide. Advantageously, the composition and material choices of the umbilical 105 confer appropriate flexibility, rigidity, and durability properties to the endoscopic cryoablation catheter 103, for use in combination with endoscopic instrumentation.

Referring now to Figure 2C, there is shown a cross-sectional view of the first end 103A of the endoscopic cryoablation catheter 103 of Figure 1. The umbilical 105 comprises the delivery conduit 113, the exhaust conduit 114, and the insulating conduit 115.

A fitting 120 connects the connector 109 to the umbilical 105. In this example, the fitting 120 provides an inlet for the delivery conduit 1 13, an outlet for the exhaust conduit 1 14, and additionally an outlet for the insulating conduit 115.

A vacuum may be applied to the insulating conduit 1 15, preferably from the vacuum source 104, to the insulating conduit 115, which may be provided via a split or controllable flow using the fitting 120. In this way, a greater vacuum may be applied to one or other of the exhaust conduit 1 14 and the insulating conduit 115.

Advantageously, the triaxial line of umbilical 105 described in Figures 2A-2C provides an efficient method of insulation. The spent cryogenic gas within the exhaust conduit 1 14 is at a temperature between the temperature of the liquid cryogen and the temperature within the endoscope, which provides a layer of insulation between the delivery conduit 113 and the insulating conduit 1 15. In this way, the exhaust conduit 1 14 and insulating conduit 115 act together to reduce undesirable condensation on the outside of the triaxial umbilical 105.

Referring now to Figure 3A there is shown a cross-sectional view of a second embodiment of the second end 203B of the endoscopic cryoablation catheter 103 of Figure 1. The second end 203B comprises an umbilical 205, a cryoablation zone 208, a needle tip 206, and a sheath 212. The umbilical 205 comprises a delivery conduit 213, an exhaust conduit 214, and an insulating conduit 215. The exhaust conduit 214 may contain spacers 216. The arrows 217 indicate the flow of cryogenic vapour from the first end 203A to the second end 203B along the delivery conduit 213. The opposing arrows 218 indicate the flow of cryogenic vapour away from the second end 203B towards the first end 203A along the exhaust conduit 214.

In this example, the insulating conduit 215 is provided by a material with low thermal conductivity, such as an insulating material with a polymeric composition. In use, the insulating conduit 215 reduces undesirable condensation on the outside of the tri-axial line caused by low temperature cryogenic vapour in the exhaust conduit 214.

Referring now to Figure 3B there is shown a cross-sectional view of a second embodiment of the first end 203A of the endoscopic cryoablation catheter 103 of Figure 3A. A fitting 220 connects the connector 109 to the umbilical 205, which comprises the delivery conduit 213, the exhaust conduit 214, and the insulating conduit 215. The fitting 220 comprises an inlet for the delivery conduit 213 and an outlet for the exhaust conduit 214 only. The insulating conduit 215 is composed of a material of low conductivity and is sealed. Referring now to Figure 4A there is shown a cross-sectional view of a third embodiment of the second end 303B of the endoscopic cryoablation catheter 103 of Figure 1. The second end 303B comprises an umbilical 305, a cryoablation zone 308 and a needle tip 306. The umbilical 305 is a biaxial line comprising a delivery conduit 313 and an exhaust conduit 314. The delivery conduit 313 and is situated within the concentric exhaust conduit 314. The exhaust conduit 314 contains spacers 316. The arrows 317 and 318 show the direction of flow of cryogenic vapour within the umbilical 305 when the cryoablation apparatus 100 is in use.

Referring now to Figure 4B there is shown a cross-sectional view of an embodiment of the first end 303A of the endoscopic cryoablation catheter 103 of Figure 1 for use with the embodiment of second end 303B in Figure 4A. The umbilical 305 comprises the delivery conduit 313 and the exhaust conduit 314. The delivery conduit 313 is in free communication with the secondary liquid cryogen chamber 102. The exhaust conduit 314 has an outlet 321 which is connected directly to the exhaust line 1 10. The exhaust line 110 is in free communication with the vacuum source 104. In use, the exhaust conduit 314 acts to insulate the endoscopic cryogenic catheter 103. The spent cryogenic vapour is at a higher temperature than the cryogenic vapour within the delivery conduit 313, which insulates the delivery conduit 313. This acts to prevent damage to the endoscopic apparatus being used in combination with the apparatus.

In all the embodiments described, in use the vacuum source 104 is a source of negative pressure compared to that of atmospheric pressure. The vacuum source 104 is configured to draw cryogenic vapour from the secondary liquid cryogen chamber 102 along the delivery conduit 1 13, 213, 313 of the umbilical 105, 205, 305 to the second end 103B, 203B, 303B of the endoscopic cryoablation catheter 103 to cool the cryoablation zone 108, 208, 308. The spent cryogenic vapour is then drawn along the exhaust conduit 114, 214, 314 towards the first end 103A, 203A, 303A of the endoscopic cryoablation catheter 103 by means of the vacuum source 104. If present, the insulating conduit 215 may be continuously evacuable by the vacuum source 104. The vacuum source 104 may vent to the atmosphere, generally by a scavenging connection to meet safety requirements. For example, the scavenging connection may include a filter and/or absorbers to trap hazardous impurities in the cryogenic gases. In all embodiments, there may be heating elements present within the umbilical 105, 205 and 305. The heating elements may be provided by electrical wires or by other means along the entire longitudinal length of the umbilical 105, 205 and 305. The heating elements may reduce or eliminate risk of damage to non-target tissue areas as well as to an independently operated endoscope.

The delivery conduit 113, 213, 313 is composed of a suitable material for delivering cryogenic gases along the umbilical 105, 205, 305. For example, a suitable material may be stainless steel. The exhaust conduit 114, 214, 314 may be composed of polyamide, or another flexible material, for example, of polymeric composition. The umbilical 105, 205, 305 may be composed of a flexible material, for example, a material with a polymeric composition. This aids the flexibility and steerability of the endoscopic cryoablation catheter 103 so that target areas of unwanted tissue may be reached when the cryoablation apparatus 100 is used with endoscopic or colorectal scope instrumentation. The cryoablation zone 108, 208, 308 of the endoscopic cryoablation catheter 103 is thermally conductive and thus is operable as a heat exchanger. The outer surface of the region defining the cryoablation zone 108, 208, 308 of the endoscopic cryoablation catheter 103 is a thermally conducting substance, for example gold, which is both conductive and sterilisable.

The needle tip 106, 206, 306 of the endoscopic cryoablation catheter 103 is sharp and able to penetrate the wall of the stomach to reach the targeted pancreatic tissue. Advantageously, movable sheaths may also be incorporated into the cryoablation apparatus 100, which the operator can move longitudinally up and down the endoscopic cryoablation catheter 103 to cover and uncover the cryoablation zone 108, 208, 308. This acts to prevent damage to the endoscopic apparatus being used in combination with the apparatus.

Referring now to Figure 5 there is shown the secondary liquid cryogen chamber 102 connected to a portion of the delivery line 11 1. The secondary liquid cryogen chamber 102 is supplied with liquid cryogen 121 from the primary liquid cryogen chamber 101 along the delivery line 1 11. The secondary liquid cryogen chamber 102 has a head space 122 defined by the volume within the secondary liquid cryogen chamber 102 which is not occupied by the liquid cryogen 121.

The cryoablation apparatus 100 is compatible with any number of cryogens including nitrogen, argon, nitrous oxide or helium. Preferably, the delivery line 11 1 is permanently insulated, for example, with a permanent vacuum jacket and/or other insulation. The delivery line 1 11 may be less than 2m, say less than 1.75, or 1.5, 1.4, 1.3, 1.2, 1.1 or 1.0m in length.

Preferably, the secondary liquid cryogen chamber 102 is filled with liquid cryogen 121 from the primary liquid cryogen chamber 101 prior to commencing cryosurgery. The secondary liquid cryogen chamber 102 may comprise a thermocouple 123 and/or a content measuring device 124. Preferably the content measuring device 124 may be operable to automatically control the flow of cryogen from the primary liquid cryogen chamber 101 to secondary liquid cryogen chamber 102. Liquid cryogen 121 may be supplied from the primary liquid cryogen chamber 101 to the secondary liquid cryogen chamber 102 by means of a pump or a vacuum source 104. Optionally, a propellant gas may be employed to supply liquid cryogen from the primary liquid cryogen chamber 101 to the secondary liquid cryogen chamber 102 (which may be that described in WO2014068262 (A1)). Within the secondary liquid cryogen chamber 102, the liquid cryogen 121 may undergo a partial phase change to become a mixture of liquid and cryogenic vapour. A heater or heating elements 125 may be provided within the secondary liquid cryogen chamber 102 to boil a fraction of the liquid cryogen 121. Optionally, the secondary liquid cryogen chamber 102 may also contain a sintered dispersive medium 126 to aid boiling of the liquid cryogen 121. The dispersive medium 126 provides a plurality of nucleation sites to encourage nucleation, boiling and/or evaporation of the liquid cryogen 121. In use, this enables cryogenic vapour to be drawn from the head space 122 of secondary liquid cryogen chamber 102 to the endoscopic cryoablation catheter 103 to effect cooling. The dispersive medium 126 may be made from sintered aluminium, cooper, brass, or other metals. Alternatively, the sintered material may be made from ceramic, plastic, or any other material suitable for sintering. Of course, other materials which provide plural, preferably tortuous pathways for the passage of cryogen and boiling thereof to enhance the dispersion of the cryogen throughout the dispersive medium, may be used for the dispersive medium.

In use, the cryogenic vapour is drawn from the head space 122 in the secondary liquid cryogen chamber 102, under the influence of the negative pressure provided by the vacuum source 104, into the umbilical 105, 205, 305 along the delivery conduit 113, 213, 313 towards the cryoablation zone 108, 208, 308 to effect cooling. The spent cryogen is drawn towards the first end 103A, 203A, 303A through the exhaust conduit 114, 214, 314 of the umbilical 105, 205, 305, into the exhaust line 110 towards the vacuum source 104.

Advantageously, this avoids, or reduces the need to provide a pressure source, i.e. a source of positive pressure compared to that of atmospheric pressure, to force the cryogenic vapour to the endoscopic cryoablation catheter 103 from the secondary liquid cryogen chamber 102.

Advantageously, the presence of the secondary liquid cryogen chamber 102 allows for the generation of cryogenic vapour from liquid cryogen 121 , which has drawn from the primary liquid cryogen chamber 101 in use. The cryogenic vapour may be drawn from the head space 122 and delivered to the endoscopic cryoablation catheter 103 along the umbilical 105. Cryogenic vapour provides more effective cooling to the cryoablation zone 108, 208, 308 and is advantageously delivered at a lower pressure than liquid cryogens. Therefore, the cryoablation apparatus 100 can be considered to be safer and more efficient.

More advantageously, the pressure differential between the cryogenic vapour in the secondary liquid cryogen chamber 102 and the exhaust cryogen in the exhaust conduit 1 14, 214 is lower than that of a Joule-Thomson device. This means there are fewer safety issues associated with high pressure liquid cryogen and large volumes of gas within the patient, if damage to the cryoablation apparatus 100 were to occur.

An optional throttle 109a is positioned between the secondary liquid cryogen chamber 102 and the connector 109. The throttle 109a is adjustable, for example by an operator, to control the flow of cryogenic vapour therethrough. The throttle 109a comprises a valve. Advantageously, by controlling the flow of cryogenic vapour we have found that the amount of moisture or other contaminants within the flow may also be controlled. Although the throttle 109a is shown positioned between the secondary liquid cryogen chamber 102 and the connector 109 this need not be the case and in embodiments the throttle 109a may be positioned at any suitable location within the cryogenic vapour flow path.

The cryoablation apparatus 100 is intended to be integrated or compatible with endoscopic instrumentation for the selective destruction of tumours and unwanted tissue in the treatment of pancreatic cancer. Previous endoscopic cryoablation apparatus suffered from the drawback of inefficient cooling. The cryoablation apparatus 100 of the present invention is designed to provide the physician with an efficient method of accurately targeting tumours or unwanted tissue in the treatment of pancreatic cancer, whilst reducing damage to surrounding healthy tissue.

Claims

1. A cryoablation apparatus comprising a primary liquid cryogen chamber, a secondary liquid cryogen chamber in selective or free communication with the primary cryogen chamber, an endoscopic cryoablation catheter and a vacuum source, the endoscopic cryoablation catheter having a first end and a second end, a cryoablation zone being provided at the second end, an umbilical extending between the first end and the second end, wherein the secondary liquid cryogen chamber is located at, adjacent or proximate the first end and, in use, the vacuum source is configured to draw cryogenic vapour from the secondary liquid cryogen chamber along the umbilical to the second end to cool the cryoablation zone and thence along the umbilical towards the first end.

2. An apparatus according to Claim 1 , comprising a throttle for controlling, in use, the flow of cryogenic vapour drawn from the secondary liquid cryogen chamber along the umbilical to the second end of the endoscopic cryoablation catheter.

3. An apparatus according to Claim 2, wherein the throttle is adjustable and comprises a valve means.

4. An apparatus according to any preceding Claim, wherein the vacuum source is connected to or in communication with the endoscopic cryoablation catheter by or via an exhaust line.

5. An apparatus according to any preceding Claim, wherein the endoscopic cryoablation catheter is between 1 to 6 meters in length, e.g. 1 to 4 meters, say 1 to 2 meters in length.

6. An apparatus according to any preceding Claim, wherein the endoscopic cryoablation catheter comprises a handle and the distance between the midpoint of the handle and the first end is between 1 to 4 meters, e.g. between 1 to 2 meters, say 1 meter.

7. An apparatus according to Claim 6, wherein the handle has a length of between 10 to 20 cm, e.g. 15cm.

8. An apparatus according to any preceding Claim, wherein the endoscopic cryoablation catheter comprises a needle tip at its second end.

9. An apparatus according to any preceding Claim, wherein the umbilical comprises a tri-axial line comprising a delivery conduit, an exhaust conduit and an insulating conduit.

10. An apparatus according to Claim 9, wherein the delivery conduit, exhaust conduit and insulating conduit are concentric.

1 1. An apparatus according to Claim 9 or 10, wherein the delivery conduit, exhaust conduit and/or insulating conduit comprise one or more spacing members therewithin.

12. An apparatus according to any preceding Claim, wherein the endoscopic cryoablation catheter has a diameter at its second end of between 1 and 5mm, preferably of between 1 and 3mm.

13. An apparatus according to any preceding Claim, wherein the secondary liquid cryogen chamber comprises a heater or heating element or a dispersive medium configured to aid with boiling of liquid cryogen.

14. A method of cooling the end of an endoscopic catheter to cryoablation temperatures, the method comprising providing a chamber containing a liquid cryogen at, adjacent or proximate a first end of an endoscopic catheter, the endoscopic catheter having a second end providing a cryoablation zone and an umbilical extending between the first end and the second end, and using a low pressure to draw cryogenic vapour from the chamber along the umbilical to the second end to cool the cryoablation zone and thence from the second end towards the first end.

15. A method according to Claim 14, comprising boiling a portion of the liquid cryogen contained in the chamber into cryogenic vapour.

16. A method according to Claim 14 or 15, comprising supplying liquid cryogen from a further chamber to the chamber.

17. A method according to any of Claims 14 to 16, comprising drawing cryogenic vapour under the influence of negative pressure provided by a vacuum source.

18. A method of treating a tumour, the method comprises inserting a catheter endoscopically into a patient and guiding it to a site of use, locating the end of the catheter in the tumour, utilising a source of low pressure to draw cryogenic vapour from an upstream store of liquid cryogen through and along the catheter to the end of the catheter, thereby to cool the end of the catheter and cryogenically treat the tumour, and thence back along the catheter in an exhaust conduit.