WO2009010964A2 - Methods and apparatus for treating the prostate - Google Patents
Methods and apparatus for treating the prostate Download PDFInfo
- Publication number
- WO2009010964A2 WO2009010964A2 PCT/IL2008/000973 IL2008000973W WO2009010964A2 WO 2009010964 A2 WO2009010964 A2 WO 2009010964A2 IL 2008000973 W IL2008000973 W IL 2008000973W WO 2009010964 A2 WO2009010964 A2 WO 2009010964A2
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- vein
- prostate
- optionally
- catheter
- deferential
- Prior art date
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M25/00—Catheters; Hollow probes
- A61M25/0067—Catheters; Hollow probes characterised by the distal end, e.g. tips
- A61M25/0068—Static characteristics of the catheter tip, e.g. shape, atraumatic tip, curved tip or tip structure
- A61M25/007—Side holes, e.g. their profiles or arrangements; Provisions to keep side holes unblocked
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M25/00—Catheters; Hollow probes
- A61M25/01—Introducing, guiding, advancing, emplacing or holding catheters
- A61M25/09—Guide wires
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M25/00—Catheters; Hollow probes
- A61M25/10—Balloon catheters
- A61M25/1011—Multiple balloon catheters
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M29/00—Dilators with or without means for introducing media, e.g. remedies
- A61M29/02—Dilators made of swellable material
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B18/00—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body
- A61B18/02—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by cooling, e.g. cryogenic techniques
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B18/00—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body
- A61B18/04—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by heating
- A61B18/12—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by heating by passing a current through the tissue to be heated, e.g. high-frequency current
- A61B18/14—Probes or electrodes therefor
- A61B18/1492—Probes or electrodes therefor having a flexible, catheter-like structure, e.g. for heart ablation
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B18/00—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body
- A61B18/18—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by applying electromagnetic radiation, e.g. microwaves
- A61B18/20—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by applying electromagnetic radiation, e.g. microwaves using laser
- A61B18/22—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by applying electromagnetic radiation, e.g. microwaves using laser the beam being directed along or through a flexible conduit, e.g. an optical fibre; Couplings or hand-pieces therefor
- A61B18/24—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by applying electromagnetic radiation, e.g. microwaves using laser the beam being directed along or through a flexible conduit, e.g. an optical fibre; Couplings or hand-pieces therefor with a catheter
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M25/00—Catheters; Hollow probes
- A61M25/01—Introducing, guiding, advancing, emplacing or holding catheters
- A61M25/09—Guide wires
- A61M2025/09175—Guide wires having specific characteristics at the distal tip
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M25/00—Catheters; Hollow probes
- A61M25/01—Introducing, guiding, advancing, emplacing or holding catheters
- A61M25/09—Guide wires
- A61M2025/09175—Guide wires having specific characteristics at the distal tip
- A61M2025/09183—Guide wires having specific characteristics at the distal tip having tools at the distal tip
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M25/00—Catheters; Hollow probes
- A61M25/10—Balloon catheters
- A61M2025/1043—Balloon catheters with special features or adapted for special applications
- A61M2025/1052—Balloon catheters with special features or adapted for special applications for temporarily occluding a vessel for isolating a sector
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M25/00—Catheters; Hollow probes
- A61M25/10—Balloon catheters
- A61M2025/1043—Balloon catheters with special features or adapted for special applications
- A61M2025/1095—Balloon catheters with special features or adapted for special applications with perfusion means for enabling blood circulation while the balloon is in an inflated state or in a deflated state, e.g. permanent by-pass within catheter shaft
Definitions
- Some embodiments of the invention relate, inter alia, to treatments of the prostate. Some embodiments relate to treatment of veins linked to the prostate venous system.
- a prostate in an adult male may develop disorders such as benign prostate hyperplasia (BPH) or prostate cancer.
- BPH benign prostate hyperplasia
- Fig. 1 schematically illustrates a typical testicular and prostate venous drainage system of a human male.
- One drainage path from testes 104 comprises a pampiniform plexus 1 18 to a left internal spermatic vein 102 or right internal spermatic vein 130 that lead towards an inferior vena cava 106 through one-way valves 108.
- valves 108 facilitate venous blood flow upwards towards an inferior vena cava 106, and inhibit back flow down to a testis 104.
- Another drainage path comprises a sequence of a pampiniform plexus 118 to a deferential vein 1 10, a vesicular vein 112, an internal iliac vein 1 14 and a common iliac vein 1 16 towards an inferior vena cava 106.
- the latter path is shared by a prostate 120 drainage path from a vesicular plexus 128 towards vesicular vein 1 12 and onwards.
- FIG. 2 schematically illustrates typical testicular and prostate venous drainage paths in a normal left side of a human male where the arrows directions illustrate the venous blood flow as described above.
- one-way valves 108 in internal spermatic vein 102 block back flow down to testes 104, they isolate hydrostatic pressure from the sections between them, so that a typical pressure at an entry 142 to left internal spermatic vein 102 is about 5-6 mmHg and may be somewhat lower at an entry 144 to right spermatic vein 130.
- the venous blood emerging from the testes has, relative to other regions of the venous system, high concentration of testosterone secreted by the testes, and particularly free testosterone that eventually dilutes in the blood circulation and binds with proteins to form a bound serum testosterone.
- the following articles relate in general to the subject of varicocele, male infertility and treatment and/or venous embolism.
- Gat Yigal, Varicocele A bilateral disease. Thesis Defense for the PhD in The Medical Sciences, 19, Dec.2006, Ghent University Hospital, Ghent, Belgium.
- a broad aspect of some embodiments of the invention relates to the recognition that excessive hydrostatic pressure (abnormal high pressure) in the testicular and prostatic veins (e.g., close to or higher than testicular arterial pressure), due, for example, to impaired valves in the internal spermatic veins, can play a causative role in prostate disorders such as BPH, cancer, and/or testosterone deficiency, possibly as outlined below.
- occlusion of one or more veins in the abdomen or inguinal region reduces the excessive hydrostatic pressure and/or testicular venous backflow into the pampiniform plexus and/or the prostate.
- the term 'cancer' or metastases thereof relate to abnormal cells that (a) develop and proliferate responsive to androgen, and/or (b) that are diminished or annihilated or suppressed, and in some cases healed, responsive to deficiency of androgen and/or responsive to treatment of androgen antagonist (antiandrogen).
- the androgen typically comprises testosterone or derivatives thereof, and in some cases particularly free testosterone or dehydrotestosterone (DHT).
- An aspect of some embodiments of the invention relates to treatment procedures related to the prostate.
- a treatment is directed to prostate cancer.
- a treatment is directed to metastases of a prostate cancer.
- a treatment is directed to forestalling and/or preventing the development of prostate disorders.
- An aspect of some embodiments of the invention relates to combining pharmaceutical treatment of prostate cancer with venous blockage.
- the use of venous blockage enhances an anti-androgen or other anti-cancer treatment.
- androgen levels may be reduced less than in the art, if a direct connection between testis and prostate is blocked.
- it is a target of treatment to maintain a minimal serum level of androgens that is higher than in art, and, for example, less likely to cause bodily harm.
- new regimens and/or new dosage levels of existing anti-androgen drugs are provided.
- anti-androgen treatments are avoided if the presence of venous backflow from a testis to a prostate is believed to exist.
- some embodiments of the invention allow one to avoid placing the prostate in a state of elevated but not hyper-elevated testosterone level, which state might enhance the production of metastases and/or androgen-resistant tumors.
- the timing of the procedure(s) and application of anti-androgen or other chemotherapeutic treatment is selected so that the combined effect is synergetic and/or at least not interfering between the two types of treatment.
- radiation treatment is started when androgen levels in prostate are still high (and tissue possibly undergoing active proliferation) and after a time, for example, a few days or weeks, venous reflux is stopped and/or anti-androgen provided.
- the apparatus comprises an intravascular catheter for sclerotherapy, designed to apply the sclerosing material into the opening of a branching blood vein.
- the catheter extends an injection means sides into such a branch.
- the catheter is configured to detect the position of the branch optionally mechanically and/or using imaging.
- An aspect of some embodiments of the invention relates to a tool designed for selective engagement of a vein, from an outside thereof.
- the apparatus is configured to separate and occlude a vein in a subcutaneous operation, from outside the vein.
- the apparatus comprises an extension which curves when it engages a vein.
- the term 'rich in' denotes a concentration of a substance relative to and beyond a normal limit, such as twice or more than the normal limit.
- the term 'excessive' or 'high' denotes a measure (e.g. a quantity or amount) relative to and beyond a normal limit, such as twice or more than the normal limit. For example, an excessive or a high pressure or a high concentration.
- the term 'normal' denotes a measure (e.g. a quantity or amount) in a range as typically found in healthy persons or organs.
- the term 'distal' denotes a direction towards the body internals and the term 'proximal' denotes the opposite direction with respect to a treatment apparatus.
- treating when used in general terms includes abrogating, substantially inhibiting, slowing or reversing the progression of a condition, substantially ameliorating clinical or aesthetical symptoms of a condition or substantially preventing the appearance of clinical or aesthetical symptoms of a condition.
- a method for treating the prostate comprising:
- the abnormal cells are localized in the prostate.
- the androgen comprises testosterone.
- the testosterone comprises one or both of free testosterone and dehydrotestosterone.
- occluding an internal spermatic vein comprises occlusion of the left and right internal spermatic veins.
- the method comprises administration of antiandrogen medication.
- the antiandrogen medication is administered locally to the prostate.
- the administration of antiandrogen follows the occlusion.
- occlusion of an internal spermatic vein comprises occlusion a junction between the internal spermatic vein and the pampiniform plexus.
- the method comprises application of at least one of chemotherapy, radiotherapy, brachytherapy, thermotherapy or cryotherapy.
- a method for treating metastases comprising:
- reducing pressure in the prostate comprises occluding a vein between the prostate and a pampiniform plexus.
- the vein is a least one of a deferential vein or a vesicular plexus.
- an abnormally high pressure is maintained in the internal spermatic veins.
- the method comprises comprising administration of antiandrogen medication.
- the administration of antiandrogen follows the occlusion.
- the method comprises comprising application of at least one of chemotherapy, radiotherapy, brachytherapy, thermotherapy or cryotherapy.
- a method for a preventive treatment of the prostate comprising:
- preventing venous reflux to the prostate comprises occluding an internal spermatic vein.
- occluding an internal spermatic vein comprises occlusion of the left and right internal spermatic veins.
- prostate disorder comprises one of BPH and cancer.
- assessing comprises assessing varicocele.
- varicocele is assessed by testicular temperature.
- assessing comprises determining at least one of PSA level, prostate size or venous anatomy.
- an intravascular catheter configured to apply material sideways from a first vein into a second vein branching from the first vein, comprising:
- the catheter comprises at least one guiding element configured to support a positioning of the orifice in front of an opening of the second vein.
- the at least one guiding element comprises a guide wire in the lumen movable into the orifice and the opening of the second vein.
- the at least one guiding element comprises at least one radio opaque element located about the perimeter of the orifice.
- the catheter comprises at least one expandable and retractable element capable of blocking material drainage along the outside of the catheter.
- the expanded at least one element is configured to fixate the catheter to the first vein walls.
- the material comprises a sclerosant.
- the material comprises a coil.
- an apparatus configured for a combined separation and sealing of a vein, comprising a tube with a lumen, and configured to selectively curve and loop at a distal section thereof, said loop having an inner diameter of less than 2 mm, said tube having a width smaller than 2 mm.
- the separation comprises separation of at least a part of the vein from connecting tissues and said distal section is configured for such separation.
- the vein is a deferential vein and the connecting tissues comprise a vas deferens.
- said lumen is adapted for providing temperature induced sclerosis.
- the apparatus comprises a filament in a distal section of the lumen, configured for heating the distal section of the tube.
- the apparatus comprises a control wire adapted to maneuver and shape the tube to enable separation of and looping around at least a part of the vein.
- the distal end is tapered to support a separation of at least a part of the vein from connecting tissues.
- an apparatus configured for a combined separation and sclerosing of a vein, comprising:
- a sclerosant injector adapted for insertion in the lumen and piercing the vein when said arms grip a vein.
- the arms are adapted to controllably open and close a grip.
- at least one arm is configured for separating at least a part of the vein from connecting tissues.
- the vein is a deferential vein and the connecting tissues comprise a vas deferens.
- the vein is the deferential vein.
- the apparatus comprises a control wire which controls said gripping.
- a method for vein sclerosis comprising: (a) maneuvering a catheter to a first vein from which a second vein branches; and
- maneuvering comprises positioning the orifice in front of an opening of the second vein.
- the method comprises fixing at least a part of the catheter to the first vein wall.
- the first vein is a vesicular vein.
- the first vein is a pampiniform plexus.
- the second vein is a deferential vein.
- the second vein is a vesicular plexus vein.
- a method for vein sealing comprising:
- subcutaneously accessing a vein comprises a accessing via a tube.
- the vein is a deferential vein and the connecting tissues comprise a vas deferens.
- separating at least a part of the vein comprises curving an element around the vein and moving the element.
- separating at least a part of the vein comprises gripping the vein.
- sealing the vein comprises one of (i) heating the vein, (ii) cooling the vein, or (iii) introducing a sclerosant agent into the vein.
- an anti-androgen composition for treatment of prostate cancer by achieving a prostatic androgen level of less than 20% of a normal level.
- an anti-androgen composition for treatment of prostate cancer by achieving a serum androgen level of more than 10% of a normal level and less than 90% of a normal level.
- a method of calculating a dosage of an anti-androgen treatment for prostate cancer comprising:
- an anti-androgen composition for treatment of prostate cancer in patients with a blocked internal spermatic vein.
- Fig. 1 schematically illustrates a typical testicular and prostate venous drainage system of a human male
- Fig. 2 schematically illustrates typical testicular and prostate venous drainage paths in a normal left side of a human male
- Fig. 3 schematically illustrates typical testicular and prostate venous drainage paths in a left side of a human male when the one-way valves in the internal spermatic vein do not function
- Fig. 4A schematically illustrates a catheter designed to align with the deferential vein (or another branching vein) for injecting an agent into the vein while preventing the agent from reaching other regions by an expandable element (shown in collapsed state), in accordance with some embodiments of the invention
- Fig. 4B schematically illustrates a catheter designed to align with the deferential vein (or another branching vein) for injecting an agent into the vein while preventing the agent from reaching other regions by an expandable element (shown in expanded state), in accordance with some embodiments of the invention
- Fig. 4C schematically illustrates an orifice at a distal end of the catheter of Fig. 4 A and 4B, comprising radio-opaque elements around the orifice, enabling to position the orifice at an opening of a branching vein, in accordance with some embodiments of the invention
- Fig. 5A schematically illustrates an apparatus for deploying a coil (shown in a stretched state) in the deferential vein (or another branching vein), in accordance with some embodiments of the invention
- Fig. 5B schematically illustrates an apparatus for deploying a coil (shown in a coiled state) in the deferential vein (or another branching vein) after the coil is deployed, in accordance with some embodiments of the invention
- Fig. 6A schematically illustrates a section of the deferential vein and a section of the vas deferens as they are attached to each other;
- Fig. 6B schematically illustrates a spike inserted between the deferential vein and the vas deferens, in accordance with some embodiments of the invention
- Fig. 6C schematically illustrates a spike separating the deferential vein from the vas deferens, in accordance with some embodiments of the invention
- Fig. 6D schematically illustrates a spike curling into a loop around the deferential vein separated from the vas deferens, in accordance with some embodiments of the invention
- Fig. 6E schematically illustrates a spike having a lumen with a control wire and filament with conductors, in accordance with some embodiments of the invention
- Fig. 7A schematically illustrates a tube with a hinged pair grippers at one end (shown in open position), in accordance with some embodiments of the invention
- Fig. 7B schematically illustrates a tube with a hinged pair grippers (shown in closed position around a vein) at one end, in accordance with some embodiments of the invention.
- Fig. 7C schematically illustrates a tube with hinged pair grippers (shown in closed position around a vein) at one end, and an injector inserted in the lumen piercing the vein, in accordance with some embodiments of the invention.
- the left and right side of the testicular and prostate venous drainage system of a human male are similar, where notably the left internal spermatic vein flows into the left renal vein and the right spermatic vein flows into the inferior vena cava. Unless otherwise specified, the descriptions and discussions and examples that follow apply to both the left and right side anatomies of a male.
- venous blood rich with testosterone from the testis is diverted to the deferential vein in a backward direction (retrograde, reflux), flows via the vesicular vein into the vesicular plexus, into the prostate venous plexus ('Santorini' plexus) and ultimately into and around the prostate.
- venous blood rich with testosterone from the testis is diverted to the deferential vein in a backward direction (retrograde, reflux), flows via the vesicular vein into the vesicular plexus, into the prostate venous plexus ('Santorini' plexus) and ultimately into and around the prostate.
- other retrograde pressure and/or flow pathways exits, possibly depending on the personal anatomy.
- the altered venous flow from the testis towards the prostate under the excessive hydrostatic pressure restricts the drainage of prostate veins, possibly leading to swelling (dilation) and/or hypertropy of the prostate.
- free testosterone secreted by the testes drains to the general blood circulation where it is diluted and binds (about 98%) to proteins such as SHBG (serum hormone binding globulin) and albumin.
- SHBG serum hormone binding globulin
- albumin proteins
- the reverse flow diverts free testosterone from its production site in the testis directly to the prostate, by direct flow and/or by diffusion along the veins, greatly increasing the concentration of testosterone in the gland, and particularly free testosterone or possibly other compounds of testosterone or other substances, to an excessive level far above normal levels (typically beyond the normal level of about 17nmol/l total and lOnmol/1 of free testosterone).
- a vessel between the prostate and the pampiniform plexus is occluded, for example, for forestalling and/or therapy of BPH, prostate cancer and/or metastases by preventing or impeding the reflux of testicular venous blood to the prostate.
- the vessel comprises the deferential vein or the vesicular plexus.
- the occlusion of the deferential vein or the vesicular plexus disconnects the prostate venous system from the excessive pressure at the pampiniform plexus and/or internal spermatic vein, such that: (a) the testicular venous blood rich in testosterone is impeded from reaching the prostate, thus maintaining a substantially normal blood pressures and testosterone concentration in the prostate, reducing the probability of developing disorders in a substantially healthy prostate; and (b) prostate venous blood can drain via the vesicular plexus (or other veins) up towards the vena cava, relieving the prostate of the excessive pressure and high testosterone concentration that might have developed due to the reflux, allowing an ailing prostate to recover, at least partially.
- occluding only the deferential vein (DV) or the vesicular plexus (VP) rather than, additionally or separately, occluding the internal spermatic vein with the incompetent one-way valves may have advantages for one or more of the following reasons:
- the deferential vein or the vesicular plexus can be accessed percutaneously; and (d) the testicular venous system is substantially not affected (optionally treated separately or in a later time, optionally according to assessment of the patient health), possibly preventing an increase in androgens to potential metastases.
- occlusion of the deferential vein or the vesicular plexus is indicated in case of prostate cancer and/or metastases, for example, to let the prostate recover as described herein.
- occlusion of the deferential vein or the vesicular plexus is accompanied with androgen medication and/or chemotherapy and/or radiotherapy and/or thermotherapy, optionally to reduce metastasis.
- the varicocele is treated, which prevents excessive pressure on the testies drainage as well, allowing drainage through other paths.
- the deferential vein is a thin-walled narrow and delicate vein normally about 0.1- 0.2 mm wide, and under the elevated pressure and backflow the vein may expand to a width of about 0.3-0.5 mm.
- the vesicular plexus branches are about the same widths and respond similarly to the excessive pressure.
- the deferential vein typically extends alongside the vas deferens, also a thin-walled narrow and delicate conduit.
- an opening of the deferential vein or the vesicular plexus is occluded.
- care is exercised to avoid occlusion of other veins, such as the cremasteric vein.
- treating the thin deferential vein or the vesicular plexus may require care to avoid damage to the vein or other veins or the vas deferens, and may require special equipment for occlusion. In some cases, for example, older and/or sterile patients, damage to the vas deferens is not considered critical. Alternatively, an intentional combined act of sterilization and blocking the deferential vein is carried out.
- An aspect of some embodiments of the invention relates to a procedure for treating prostate cancer, optionally and particularly localized at the prostate, comprising occlusion of an internal spermatic vein and optionally administration of antiandrogen medication.
- An aspect of some embodiments of the invention relates to a procedure for treating metastases of prostate cancer, comprising occlusion of a deferential vein or the vesicular plexus, and optionally administration of antiandrogen and/or other medication.
- An aspect of some embodiments of the invention relates to a procedure for forestalling and/or preventing prostate disorders (e.g. BPH or cancer) and/or testicular disorders (e.g. reduced testosterone production and delivery), comprising occlusion of a vein such as the internal spermatic vein and/or deferential vein and/or the vesicular plexus.
- prostate disorders e.g. BPH or cancer
- testicular disorders e.g. reduced testosterone production and delivery
- An aspect of some embodiments of the invention relates to a procedure for forestalling and/or treating disorders of the prostate (e.g. BPH or cancer), optionally and particularly avoiding recurrence of the disorder by reducing hydrostatic pressure in venous bypasses that may develop, comprising occlusion the junction of the internal spermatic vein and the pampiniform plexus.
- disorders of the prostate e.g. BPH or cancer
- An aspect of some embodiments of the invention relates to apparatus for sclerosing of the deferential vein or the vesicular plexus without inflicting damage to other vessels such as the cremasteric vein or vas deferens.
- the apparatus is configured to treat other veins branching from another vein.
- the apparatus supports reaching the vesicular vein and/or the deferential vein from the internal iliac vein.
- the apparatus comprises an intravascular catheter for sclerotherapy, configured to apply the sclerosing agent sideways into an opening of the deferential vein or the vesicular plexus, optionally limiting or avoiding agent flow to another region.
- An aspect of some embodiments of the invention relates to a medical tool configured to perform both separation and occlusion of a vein.
- the tool forms a loop or partial loop around a vein such as the deferential vein or a branch of the vesicular plexus, separating a part of the vein from other tissues or organs such as the vas deferens.
- the tube comprises heating elements for inducing occlusion of the vessel.
- the tube is flushed with hot or cold fluid at a temperature sufficient for causing the vessel's occlusion.
- the vein is treated by the wire subcutaneously in a laparoscopic-like method.
- the apparatus comprises grippers configured to hold a vein such as the deferential vein or a branch of the vesicular plexus, separating a part of the vein from other tissues or organs such as the vas deferens.
- the grippers are mounted on a tube having a lumen for inserting an injector for applying a sclerosant into the gripped vein.
- the vein is treated by the gripper subcutaneously in a method similar to laparoscopy.
- anatomy elements applies to the left and right sides.
- the labeling of the anatomy elements, unless otherwise specified, is according to
- Fig. 3 schematically illustrates typical testicular and prostate venous drainage paths in a left side of a human male when the one-way valves in the internal spermatic vein do not function normally, for example, due to mechanical deterioration such as weakening of valve substance, wearing away or aging effects.
- the following is intended to be a non-limiting description of processes which may happen with regard to venous flow.
- the methods and apparatus of some embodiments of the invention may be used independently of the correctness and/or completeness of the following discussions. Some embodiments are used and/or modified according to the flow paths and/or pressures described herein.
- internal spermatic veins 102 or 130 form continuous columns of blood in which hydrostatic pressure develops up to approximately 31 mmHg at entry 142 to left internal spermatic vein 102 approximately 27 mmHg at entry 144 to right internal spermatic vein 130 (typically about 4-6 fold the typical pressure in ordinary conditions) when the patient is in an upright position such as standing.
- This excessive hydrostatic pressure may exist in vessels connecting to internal spermatic vein 102, such as deferential vein 110 or pampiniform plexus 118, since, according to Bernoulli's law of connecting vessels, the pressure propagates from the testicular to the prostate venous drainage systems and hydro-dynamically equilibrates between both drainage systems.
- the pressure may diminish as vessels are further away from entry 142 or 144, but may be still more than the normal range of about 5 mmHg.
- the excessive pressure at entry 142 or 144 and nearby vessels will be denoted as 'EP'.
- the excessive high pressure EP inhibits the drainage of the venous blood from testes 104 and pampiniform plexus 118 up internal spermatic vein 102. Rather, the pressure differentials urge the testicular venous blood, rich in free testosterone (about 130 fold above serum level), towards vesicular plexus 128 and onwards to prostate 120; the increased pressure may also result in high pressure in the prostate and/or constrained drainage of venous blood from the prostate.
- venous blood from the testis is drained, at least partly, via other paths, such as deferential vein 110, a scrotal vein 146 or by-pass veins 136 that might have developed, possibly due to the excessive pressure.
- deferential vein 110 a scrotal vein 146 or by-pass veins 136 that might have developed, possibly due to the excessive pressure.
- a constrained circulation is maintained as venous blood drains via vesicular plexus 128 and vesicular vein 112, and to some extent, via other veins.
- prostatic veins may develop due to the high pressure in the prostate.
- the excessive pressure EP may produce at least some of the following effects on the prostate:
- (a) The venous blood that is diverted towards prostate 120 and congests and enlarges (swells) prostate 120.
- the swelling of prostate 120 may be manifested, at least partially, as BPH or other prostate problems.
- (b) The venous blood from the testes 106, rich in free testosterone (up to 5 to 10 fold, or higher such as 50 to 100 fold) bathes the prostate gland cells with free testosterone, effecting benign prostate hyperplasia (BPH).
- BPH benign prostate hyperplasia
- About 90% of the free testosterone is irreversibly converted to dehydrotestosterone (DHT), which has about five fold higher affinity for androgen receptors than free testosterone and may effect an accelerated proliferation of prostate cells.
- DHT dehydrotestosterone
- the molecule of free testosterone (and DTH) is smaller than a bound testosterone molecule (or ligand), and may more easily diffuse through the prostate gland interstitium to reach the glandular tissue cells, while the bound testosterone is blocked.
- one or more of the adverse states and effects described above may be avoided, delayed, alleviated and/or repaired, at least to some degree, by reducing or eliminating the excessive pressure EP. Reducing the excessive pressure reduces or eliminates the back flow (reflux) of venous blood, rich in free testosterone, from the testes to the prostate and/or is used to reduce EP on the testis themselves.
- the reflux that has effected the excessive hydrostatic pressures EP is prevented or impeded by occlusion (e.g. by embolization and/or sclerosis) of left internal spermatic vein 102 and/or right internal spermatic vein 130.
- occlusion e.g. by embolization and/or sclerosis
- some or all veins through which the reflux flows such as deferential vein 1 10 and vesicular plexus 128, are occluded.
- bypass veins 136 that might have developed connecting parts of internal spermatic vein 102 and/or 130, or connecting internal spermatic vein 102 and/or 130 to the renal vein are occluded, too.
- venous blood from the testes may use alternative paths to drain to the inferior vena cava, such as through scrotal vein 146, or via deferential vein 110 to vesicular vein 122.
- Arterial blood may now enter testes microcirculation 126 unimpeded, allowing recovery of damaged tissues and restoring, at least partially, testosterone production.
- the pressure in the internal spermatic vein triggers the development of by-pass veins that connect between a lower part of the internal spermatic vein and an upper part thereof or the renal vein.
- the by-pass veins may restore the excessive pressure on pampiniform plexus 118 and testis 104 with recurrence of at least some of the detrimental effects of excessive high hydrostatic pressure.
- junction 148 of internal spermatic vein 102 and/or 130 and pampiniform plexus 118 is occluded, preventing the adverse effects of the excessive pressure in the by-pass veins on the venous system of the testis and indirectly on the prostate as described above, while preventing the recurrence of the excessive pressure even if new by-pass veins are developed.
- junction 148 is occluded with a fast setting sclerosing agent.
- the agent comprises slow flowing or viscous material or a material that gels and/or foams.
- using a fast setting and/or viscous material prevents the agent from spreading to and occluding other locations, such as pampiniform plexus 118, which may result in various adverse effects.
- flowing of the sclerosant at least into nearby side-branches is encouraged, to seal such by-pass veins.
- the deferential vein and/or the vesicular plexus is occluded using microsurgery, optionally by exposing the deferential vein or the vesicular plexus.
- the surgery is conducted under ultrasound or other imaging guidance such as illumination by optical fiber.
- other veins are treated during the operation.
- the occlusion is carried out by applying sclerosants (sclerosing agents) into a vein.
- the sclerosant comprises, for example, Sodium tetradecyl sulfate in its various forms, ethyl alcohol (e.g., ethanol) or its derivatives, Onyx (TM) , PVA particles, acrylic microspheres, or any blocking agent of the art.
- the sclerosant is applied via intravenous catheter or catheters.
- the sclerosant is applied subcutaneously, such as by a catheter or a syringe.
- vascular blocking other methods of blood vessels blocking are used, such as placement of coils, or other mechanical elements such as silk (optionally coated with sclerosant or other materials) that block the vein lumen and/or induce thrombosis that blocks the vein and typically induces degeneration and permanent occlusion.
- placement of coils, or other mechanical elements such as silk (optionally coated with sclerosant or other materials) that block the vein lumen and/or induce thrombosis that blocks the vein and typically induces degeneration and permanent occlusion.
- the occlusion agent is a fast setting (curing) cyanoacrylate based glue, such as cyanoacrylate, N-butyl-2-cyanoacrylate (NBCA) ('glue'), Histoacryl®, or Glubran (TM) .
- cyanoacrylate such as cyanoacrylate, N-butyl-2-cyanoacrylate (NBCA) ('glue'), Histoacryl®, or Glubran (TM) .
- vein sealing is provided by heating and/or ablation, for example, endovascular ablation such as radiofrequency radiation that heats up the vein, or application of direct heating, is used to damage the vein and/or induce its walls to shrink and/or develop a thrombosis, optionally a complete blocking of the vessel.
- a friction against the vessel endothelium may be used to shrink and/or occlude the vessel.
- such treatment causes an inflammation reaction due to tissue damage, which enhances fiber formation.
- electrocautery such as by electric wire in a catheter, or laser heating by an optic fiber in the catheter may be used to heat and shrink the vessel and/or otherwise effect sclerosis.
- the catheter or other apparatus as described herein
- the catheter include a connector to a source of ablating material/energy.
- a control knob or switch is provided on the catheter.
- these methods are applied by minimally invasive methods such as by laparoscopy.
- the methods are applied externally such as by or radiation, for example, a plurality of laser beams is used to focus at the sclerosis region, while each beam does not damage, or negligibly damage, the other tissues whereas the convergent beams at the focus have sufficient power to shrink and/or effect sclerosis of the vein.
- electromagnetic radiation e.g. x-ray or by MRI
- ultrasound from several directions focusing at the sclerosis region may be used.
- other mechanical, biological, chemical or physical methods and/or mechanisms, or a combination of said methods and mechanism may be used to block the blood vessel.
- a temporary embolization such as by Gelfoam (TM) (dried gelatin sponge) which clots the vessel and later on dissolves may be used, alone or I conjunction with other methods.
- TM Gelfoam
- Various vessel sealing techniques as known in the art may be adapted for the sizes and/or access as described herein and used.
- the sealing is immediate.
- the sealing takes several minutes.
- a sclerosant is used for the manufacture of a medicament for affecting drainage veins in the groin area and/or forestalling and/or treating BPH or prostate cancer in a subject.
- the sclerosant is adapted to treating backflow that effects BPH and/or prostate cancer.
- the adaptation comprises the composition of materials and/or their proportions, for example, mixing two or more occlusion materials, optionally comprising temporary occlusion material such as Gelfoam (TM) .
- the medicament may comprise materials with affinity to testosterone and/or adapted to bind to and occlude vessels containing high concentration of bound and/or free testosterone.
- the high concentration comprises 5 to 10 fold, or higher (e.g. 50 to 100 fold), than the normal range of bound and/or free testosterone.
- the medication is administered systemically or locally, for example to the deferential vein.
- the materials with affinity are cleared away at low testosterone levels but cannot be cleared away fast enough at high levels.
- an antiandrogen medication such as an antigen bound guided molecular therapy may be used as part of the treatment.
- the antigen reduces testosterone production by affecting regions in the brain (e.g. hypophysis or hypothalamus) that regulate testosterone production.
- the antiandrogen comprises materials such as is LHRH analogs (luteinizing hormone- releasing hormone), administered systemically or as subcutaneous patch.
- such antiandrogen material may be a part of the medicament described above.
- the antiandrogen comprises ⁇ -reductase blocker which inhibits the conversion of free testosterone to dehydrotestosterone (DTH) which is about 5 fold more potent androgen than free testosterone.
- DTH dehydrotestosterone
- anti-androgen is provided in kit form with the sclerosant and/or other blockage means.
- anti-androgenic agent may be administered, locally or systemic, to further the healing effect.
- the additional medication may lower even more the testosterone levels without significantly affecting the patient health.
- chemotherapy, brachytherapy, radiotherapy and/or thermotherapy are used to reduce prostate cancer and/or metastases.
- deferential vein 110 or vesicular plexus 128 is occluded to block the backflow of testicular venous blood into the prostate, relieving it of the excessive pressure and/or high testosterone, and optionally allowing the prostate to recover, at least partially.
- other veins are not treated for backflow and/or varicocele, at least for a time, according assessment of the subject health and/or according to the medical diagnosis and/or medical prognosis with respect to the subject conditions.
- the prostate is relieved of the back flow by occluding deferential vein 1 10 or vesicular plexus 128.
- the prostate When deferential vein 1 10 is occluded the prostate can drain the excessive blood with high concentration of testosterone via vesicular plexus 128 and vesicular vein 122, whereas when vesicular plexus 128 is occluded the prostate can drain via other veins such as vessels such as vessels developed due to the pressure in the prostate. With the excessive venous pressure in the prostate relieved, arterial blood can more easily enter prostate microcirculation 124.
- the recovering prostatic tissue, with arterial blood with normal testosterone levels (and bound serum testosterone) can reduce the stimulus to growth of cancer tissues in the prostate (that was affected by high concentration of free testosterone).
- the prostate cells are deprived of the stimulus to proliferate, and are converted, at least partially, to normal and/or harmless cells and/or may die back.
- the prostate cells are occluded, particularly but not limited to, in case of metastases or suspicion for metastases.
- vesicular vein 114 or other veins such as developed veins due to the pressure in the prostate
- vesicular vein 114 or other veins such as developed veins due to the pressure in the prostate
- testosterone generation and/or drainage to the bloodstream via internal spermatic veins 102/130 is inhibited by the excessive pressure EP, testosterone production and supply to the bloodstream is reduced, reducing the risk for metastases proliferation by high concentration of testosterone, and particularly of free testosterone.
- the occlusion treatments are useful in forestalling prostate cancer metastases by either (a) occlusion as described above, preventing the development of cancer, and hence, metastases, or (b) if BPH or cancer is already present, occlusion (e.g. by microsurgery) of at least the deferential vein or other vessels that drain from the prostate to the blood stream, possibly allowing the prostate to heal (at least partly) as described above.
- occlusion blocks at least some of the venous passage from the prostate and consequently reduces possible leakage of cancerous cells from the prostate that may settle at certain organs and, additionally, may reduce testosterone supply to the bloodstream, reducing the risk of proliferation of metastases.
- prostate enlargement caused by pressure is distinguished from enlargement caused by proliferation by manipulation of the prostate to feel its texture and/or elasticity and/or by tracking reduction in volume and/or PSA over time.
- PSA does not go down and/or prostate is stiff in spite of drainage correction (e.g., volume may go down, but not close to normal), this may indicate androgen-insensitive proliferation. This may suggest immediate biopsy and/or resection and/or irradiation (or other treatment) of prostate despite lack of clinical symptoms. In alternative cases, a reversal of shrinkage and/or reoccurrence of varicocele indicates a failed procedure.
- prostate localized cancer when prostate localized cancer is detected o determined or suspected (e.g. by PSA level and/or biopsy), and metastases are not detected (e.g. by radiology or nuclear imaging methods), an occlusion of a vein connecting the prostate to the pampiniform plexus, such as the deferential vein or the vesicular plexus is indicated.
- the occlusion is accompanied by antiandrogen administration.
- antiandrogen treatment is not used, for example, when the patient develops, or suspected to develop, adverse effects or symptoms.
- the occlusion relieves the prostate as described above.
- antiandrogen medication is optionally applied to further reduce testosterone reaching the prostate.
- the antiandrogen medication is administered, at least partially, locally to the prostate and/or at least a part of the prostate environment such as vessels connecting to the prostate.
- the antiandrogen medication is applied after a delay from the occlusion, for example, a week after the occlusion of the deferential vein or the vesicular plexus.
- the delay is indicated according to surveillance of the patient condition and/or determination of the treatment effect.
- the treatment further comprises other medications, for example, chemotherapy.
- other medications for example, chemotherapy.
- radiotherapy and/or brachytherapy and/or thermotherapy and/or cryotherapy are also used.
- prostate cancer metastases when prostate cancer metastases are detected or determined (e.g. by nuclear imaging methods such as PET or SPECT), an occlusion of a vein between the prostate and pampiniform plexus is indicated:
- the vein is one of the deferential vein or the vesicular vein.
- the internal spermatic vein is not occluded, so that the testis optionally remain in a state of lower testosterone production (relative to normal conditions) due to the excessive hydrostatic pressure, and the metastases are nourished with a smaller amount of serum testosterone relative to normal conditions.
- the low concentration of testosterone causes at least some of the metastases cells to die and/or to convert to harmless cells.
- antiandrogen medication is optionally applied to further reduce testosterone in the blood circulation.
- antiandrogen treatment is not used, for example, when the patient develops, or suspected to develop, adverse effects or symptoms.
- the antiandrogen medication is applied after a delay from the occlusion.
- the delay is indicated according to surveillance of the patient condition and/or determination of the treatment effect.
- the treatment further comprises other medications, for example, chemotherapy.
- radiotherapy is used for metastases that are detected or suspected in a determined region of the body
- the metastases cells developed in a prostate having a high concentration of testosterone due to reflux as described above. Consequently, in some cases, such cells need a high concentration of testosterone for survival, and occluding only the deferential vein or the vesicular plexus and leaving the tested in reduced testosterone production by not occluding the internal spermatic veins can enhance the therapeutic effect for such cells by depriving them of normal testosterone.
- the antiandrogen further reduces the testosterone supply to the cancer cells, further depriving them from the concentration of testosterone needed for their survival.
- an anti-androgen releasing implant is provided in the differential vein and/or venous plexus, with or without occlusion. Exemplary treatment procedures including drugs for localized Prostate cancer
- the following protocol is used: 1. Treatment for Bilateral Varicocele (for example as described herein).
- the following protocol is used: 1. Treatment for Bilateral Varicocele.
- a first class of medication is AAT (ADT), LHRH agonists.
- Examples include: (a) Zoladex (injection), for example, 10.8 mg every 3 months.
- such medications are provided in conjunction with mechanical reduction of testosterone flow to the prostate.
- the dosages used are smaller and/or less frequent, for example, being applied at 80%, 70%, 50%, 30%, 20% 10% or intermediate dosages.
- the frequency is 70%, 50%, 40%, 20% or other frequency ratios.
- the frequency is made higher with dosages smaller, to allow better control over testosterone levels.
- a second class of medication is Androgen Receptor antagonists. Examples include:
- Casodex for example at 50mg xl/day, if provided with ADT (androgen deprivation therapy) and 150mg xl/day if provided without ADT.
- a third class of medications is Estrogen, for example, DES - diethyl stilbestrol, for example, Ix gr/day for a week then 0.5 gr/day twice a week
- a fourth class of medication is Anti adrenal Testosterone production, including, for example: (a) Ketokanazole 2x200mg/d
- a fifth class of medication is a combination therapy of Total Androgen Ablation (TAB/CAB), for example, LHRH plus an Antiandrogen.
- a sixth class of medication Blockades the conversion of Testosterone to DHT, for example, an alfa - reductase inhibitor (Fenasteride), for example, at 5mg/d
- a seventh class of medication is Chemotherapy, for example, Daxotrene (Docetaxel), for example, one injection/3 weeks.
- Exemplary medication targets In general, the various medications (other than chemotherapy) are used to reduce testosterone existence and/or acceptance by prostatic cancer cells, and thereby causing the reversion and/or deterioration of hormone-dependent cancer cells.
- this goal cannot generally be achieved, even by drastic reduction of serum testosterone (e.g., medical castration), as long as venous black flow (which may initially cause the disease), still exists.
- This has been also borne out by some researchers (e.g., Elahe A. Mostaghell, Stephanie T. Page, Daniel W. Lin, Ladan Fazli, lisa M. Colemanl, Lawrence D. True, Beatrice Knudsen, David L. Hess, Colleen C.
- testosterone appears to reach the prostate via the above mentioned venous system, which not only provides testosterone which is not affect by flow through the body, but may also provide free testosterone at very high levels (as blood flow time is not sufficient to cause protein-binding thereof).
- the venous flow provides up to 130 times the amount of free testosterone to the prostate than provided via an arterial serum route, even if the serum level is depressed by 95%, the level reaching the prostate will still be ⁇ 6 times the normal free testosterone level.
- anti-androgen treatment have a detrimental effect in that they may encourage cancer proliferation.
- anti-androgen treatment is provided, the testosterone levels in the prostate go down, but are still some 6 fold above normal. This means that while some cancer cells may die, others have the opportunity to evolve, possibly into forms that are less sensitive to testosterone and/or do not require such testosterone. Possible, this is caused by mutation or by another selective pressure, for example, one which allows previously less-competitive cells (those requiring and using less testosterone) to become competitive.
- prostatic cancer cells could not survive outside the prostate, due to their high-testosterone needs, once the cancer evolves, such cells can survive and metastasize. Moreover, once a cancer has reached a state where some cancer cells can live outside the prostate, this may indicate a sizable number of cells that are not super sensitive to hormone levels, inside the prostate.
- the above or other venous blockage methods are used to prevent direct and abnormal testosterone flow from the testis to the prostate.
- such blockage is performed before any anti-androgen treatment, to prevent the possibility that prostatic cells will be exposed to moderately high testosterone or above-minimal levels (caused by AAT) which might enhance their evolution. Rather, androgen levels are immediately brought down to normal (or below normal).
- the level to which androgens are brought is selected so that it will have a shock effect and will have an anti-proliferative effect on prostatic cancer cells and/or pre-cancerous cells.
- a combination of venous blockage and serum reduction is used (e.g., to compensate or overcompensate for serum increase due to treatment of varicocelle).
- a venous blockage method that does not increase testosterone production is used.
- testosterone levels in the serum are within a normal range, while simultaneously reducing prostatic levels to normal.
- both serum and prostatic levels are reduced to below normal.
- the amount of anti-androgens used are smaller than in art, as it is desired to maintain a higher serum level than was required in art.
- both serum and prostate levels are below-normal, the prostate levels set to cause healing and the serum levels set to avoid damage to body.
- Complete androgen block (CAB) absorption of testosterone production in the testes and adrenal glands
- CAB Complete androgen block (CAB) (ablation of testosterone production in the testes and adrenal glands) if used, can be, for example, to target the testis and adrenal glands by ketocanazole.
- multiple levels of prostatic testosterone are provided selectively, for example, by mechanical venous blockage and/or varying amounts of anti-androgen treatment.
- methods in accordance with exemplary embodiments of the invention can provide effective prostatic cancer suppression at multiple serum levels.
- a protocol is provided where several serum levels are tried (e.g., to assess general health at the levels), while ensuring a below-minimal prostate level is achieved for all such levels.
- an attempt is made to ensure prostate hormone levels remain high without androgen deprivation therapy (ADT), until the suggested treatment and do not dip for long periods of time, to prevent the emergence of low-testosterone sensitivity cancer cells, before cancer treatment is started.
- ADT androgen deprivation therapy
- the prostate is removed, as various anti- androgen therapies may be less effective.
- metastases treatment of CAB can be given.
- the treatment includes a feedback process.
- feedback includes performing a biopsy of the prostate to measure androgen levels in situ.
- feedback includes estimating prostate hormone levels based on a known venous backflow state and serum levels.
- feedback includes selecting dosage levels and treatment protocols according to a known state of venous backflow, for example, to provide a different treatment to a cancer patient with no venous backflow.
- feedback includes imaging and estimating testosterone levels in the prostate, for example, by mapping venous backflow (e.g., by injection of contrast material into the ISV or other veins) and viewing backflow using x-ray.
- radioactively tagged testosterone is injected into the ISV or other location and its arrival at prostate imaged using a scintillator-imager or sensor. It is a particular feature of some embodiments of the invention that prostatic hormone levels can be substantially reliably estimated from serum levels.
- the prostate is biopsied and an estimate of free testosterone, bound testosterone and/or DHT are made based on concentration per tissue unit biopsied.
- feedback on the type of tissue in the prostate is estimated base don the response of the prostate to treatment, for example, venous reflux blockage. For example, it is expected that mechanical shrinkage take effect substantially immediately and complete within a few weeks or months. Biological shrinkage can take longer.
- PSA levels go down for six months or more after BPH is treated.
- shrinkage does not continue and/or PSA levels do not go down and/or prostate does not enlarge after AAT is stopped and/or after backflow to testis is stopped, androgen-insensitive tissue is assumed to exist and resection and/or other aggressive treatment may be applied to the prostate.
- varicocele is seen to exist or recur, it is treated again.
- a delay until the veins expand sufficiently to be mapped and/or passed with a catheter is waited, for example, several months. During such time, AAT may be applied or avoided, for example, as discussed herein.
- a repeated checks for varicocele are carried out, for example, every few months and/or years, optionally with decreasing frequency, e.g., at 1 month, 3 month, 6 month, 1 year, 3 years.
- AAT is provided, such checking is carried out during treatment.
- any of the abnormal parameter values is used as a target for correction during treatment by venous blockage and/or medical treatment.
- a plurality of parameters are selected and target ranges selected for each.
- two, three, four or more parameters may be selected and various parameters of the treatment (e.g., degree of blockage, location of blockage, type of medication, dosage and/or frequency) are modified using various optimization and control methods, for example, those known in the art of medicating, to achieve or approximate the desired ranges.
- a value indicating a specific androgen activity is used instead of androgen levels, for example, combining the effects of bound testosterone, free testosterone and DHT.
- target values may be set to be within normal range (e.g., +-20%). In some cases, within a time frame of several weeks or several months normal values are not expected (e.g., for prostate volume).
- Target values may be, for example, for elevated parameters, 300% of normal, 200% of normal, 150% of normal 120% of normal 100% of normal, 80% of normal, 50% of normal or intermediate or smaller or greater values.
- range sin prostate and/or serum may be, for example, as described below, generally, "normal", “Sub-normal”, “low” ( ⁇ 5%) or very low ( ⁇ 0%).
- serum and prostate levels are linked differently after venous blockage than without such blockage and during partial or complete reflux.
- Ratio can be assessed, for example, by injecting contrast material into the testicular vein or artery and tracking its spread I the body using X-ray.
- pressure levels in the prostatic drainage less than 300%, 200%, 150%, 120% of normal values.
- the above percentages are of a nominal value, such as 5mmHg.
- a target prostate volume for example, 25 ml, 30 ml, 40 ml, 50 ml or intermediate sizes, or a reduction of, for example, 20%, 30%, 40%, 50% or intermediate values, within 1 month, 2 months, 3 months, 6 months or intermediate values.
- a serum (and thereby prostate) serum level of about 8.4 nmol/ml.
- the target level is lower, for example, 1, 2, 3, 4, 5 nmol/ml or intermediate or lower serum levels.
- higher than normal levels are desired, for example, 10, 13, 20, 30 nmol/ml or intermediate or higher values. Normal levels might depend on the age of the patient.
- prostate androgen levels are estimated based on biopsies which show prostate testosterone, free-testosterone and/or DHT levels as a function of volume, typically measured in nanograms.
- the desired levels are less than 200%, 100%, 80%, 50%, 30%, 20% of normal levels.
- the treatment includes setting a base line and setting an allowed variation, for example, 10%, 20%, 30%, 40%, 50% or intermediate or greater amounts, and tracking the serum levels, for example, daily, bi- daily, weekly, bi-weekly or at other higher or lower frequencies to adjust an anti- androgen treatment.
- AAT is provided at a lower dosage and higher frequency to better track such measurements and avoid too low and too high serum and/or prostate androgen levels.
- feedback and target values as described herein are used for treating prostate cancer with only venous blockage treatment and/or only treatment without venous blockage.
- it is used for combined treatment including vein blocking and one or more of chemotherapy, radiation, cryoablation, heating and/or focused ultrasound.
- An additional exemplary regimen for Metastatic Prostate cancer without previous anti-androgen treatment is as follows: (a) block venous backflow to prostate.
- a stronger AAT is used, for example, down to 4%-%% or even lower, such as 3%, 2%, 1% or less.
- CAB is applied closer to toxic concentrations, for example, ketocanazole 200x4 /d.
- a single shot of AAT is provided, for example, a single injection of GNRH analog, that has an effect for ⁇ 3 months rather than 6 months.
- a biopsy shows maintenance of cancerous and/or pre-cancerous cells, an additional shot is given.
- the dosage is reduced (e.g., by 60%, 50%, 40% or intermediate or greater amounts) and applied more frequently (e.g., taking into account the half life of injected medication) thus allowing a higher serum level of androgen to be maintained.
- a vacation is provided between multiple applications, to allow the body to recover.
- a preventive treatment is applied to a subject in order to prevent the development of prostate disorders such as BPH and cancer.
- subjects are screened for prostate disorder risks or for early stages of prostate disorders.
- the screening comprises detection or determination of uni-lateral (left or right side) or bi-lateral (left and right side) varicocele of the internal spermatic veins and/or testicular veins.
- the risks are assessed by measuring the testis temperature, wherein elevated temperature optionally indicates varicocele.
- elevated temperature optionally indicates varicocele.
- the external temperature of the testicular sack is measured.
- a thermograph is used for external measurement of the testes temperature.
- a temperature over 32°C is an indication of a varicocele, such as 32.5 0 C or above.
- a temperature over 34 0 C is an indication of a varicocele.
- a temperature over 36 0 C is an indication of a varicocele.
- a temperature over 37°C is an indication of a varicocele.
- a temperature between the indicated temperatures is an indication of a varicocele.
- concentration of PSA and/or other markers are used to assess prostate disorder risks or early stages of prostate disorders.
- venography and/or ultrasound is used to determine or assess varicocele and/or venous anatomy and/or prostate anatomy.
- an enlarged and/or congested prostate may indicate a risk for prostate disorders, or distended veins may indicate varicocele.
- the preventive treatment comprises occlusion of the internal spermatic vein 102 and/or right internal spermatic vein 130, so that that the excessive hydrostatic pressure developed in the varicose internal spermatic veins is blocked. The reflux of high pressure venous blood rich in testosterone is prevented from reaching the prostate, enabling a congested prostate and/or a prostate with hyperplasia to recover as described above.
- the preventive treatment comprises occlusion of junction 148, left internal spermatic vein 102, pampiniform plexus 1 18 and/or junction 148 of right internal spermatic vein 130 and pampiniform plexus 1 18. Occluding the junction may be advantageous by preventive the recurrence of excessive hydrostatic pressure in the pampiniform plexus (and resultant effects) due to the development of by-pass veins that connect between a low part of the internal spermatic vein and an upper part of the vein or the renal vein.
- junction 148 is occluded with fast drying agent such cyanoacrylate based glue as described above.
- fast drying agent such cyanoacrylate based glue
- anti-androgen therapy is provided, for example, for between 1-10 months for example, for 6 months, to ensure that no pre-cancerous cell and/or abnormal cells that may have been encouraged by the high-testosterone state, remain.
- anti-androgen therapy is applied even if no prostate enlargement is found, for example, if varicocele has existed for a considerable period of time, such as 1 year, 5 years, 10 years or more. Occlusion of the deferential vein
- occlusion of the deferential vein is indicated in case of prostate cancer metastasis.
- the occlusion of the deferential vein disconnects the prostate venous system from the excessive pressure at the pampiniform plexus and/or internal spermatic vein, such that:
- testicular venous blood rich in testosterone is impeded from reaching the prostate, thus maintaining normal blood pressures and testosterone concentration in the prostate, reducing the probability of developing disorders in a substantially healthy prostate; and (b) prostate venous blood can drain via the vesicular plexus up towards the inferior vena cava, relieving the prostate of the excessive pressure and high testosterone concentration, allowing an ailing prostate to recover, at least partially, as described above.
- occluding only the deferential vein rather than, additionally or separately, occluding the internal spermatic vein may have advantages for one or more of the following reasons:
- the deferential vein can be reached via the femoral vein and iliac veins to the vesicular vein relatively easily with respect to reaching up the abdomen and down the internal spermatic vein;
- testicular venous system is substantially not affected, optionally maintaining the reduced testosterone production, optionally depriving metastases cells of testosterone for their existence and proliferation.
- the internal spermatic vein or other veins are treated separately or in a later time, for example, according to a determination of the patient condition.
- the deferential vein is a thin-walled narrow and delicate vein normally with a width of about 0.1-0.2 mm, and under the elevated pressure and backflow the vein may expand to a width of about 0.3-0.5 mm.
- the deferential vein is typically attached to the vas deferens, also a thin and narrow- walled delicate vessel.
- an opening of the deferential vein is occluded.
- treating the deferential vein may require care to avoid a damage to the vein or other veins or the vas deferens, and may require special equipment for occlusion.
- the deferential vein is occluded with the apparatus described below.
- Vesicular plexus 128 has one or more branches. Typically, all the branches have to be occluded in order to impede the reflux from pampiniform plexus 118. In exemplary embodiments of the invention, vesicular plexus 128 branches are occluded as described above, optionally, with the apparatus described below.
- the vesicular plexus is not attached to the vas deferens, which may be advantageous, yet all the branches of the vesicular plexus have to be occluded which may prolong and/or complicate the treatment. Occluding a vein opening
- a prostate treatment may require occluding a vein between pampiniform plexus 118 and prostate 124, such as deferential vein 110 or vesicular plexus 128.
- a vein is occluded at its opening, such as the opening of deferential vein 110 or the vesicular plexus 128 into vesicular vein 112, or the opening of deferential vein 110 into pampiniform plexus 118.
- the sclerosant is optionally applied only to the vein or its opening, excluding access of the sclerosant to other regions, that is, preventing the sclerosant from flowing in vesicular vein 112 or pampiniform plexus 118.
- a special catheter is used which is particularly adapted to perform occlusion of a vein opening only.
- deferential vein 422 (110) is referred to as an example of a vein branching from another vein and vesicular vein 420 (112) is referred to as an example of a vein into which a branching vein opens.
- Fig. 4A schematically illustrates a catheter 400 designed to align with an opening of the deferential vein and to inject a sclerosing agent into the deferential vein, while preventing the agent to reach other regions of the vesicular vein by an expandable element shown in collapsed state, in accordance with some embodiments of the invention.
- Fig. 4B illustrates catheter 400 showing the expandable element in expanded state, in accordance with some embodiments of the invention.
- catheter 400 is configured to apply a sclerosant at an opening of the deferential vein of a width of about or less than about 0.5 mm, such as about 0.4 mm or about 0.3 mm.
- catheter 400 comprises a tube 410 having a lumen 412 with an orifice 416 adapted to adhere to and inject a sclerosant to the opening of the deferential vein.
- orifice 416 is located at the side of tube 410 near the distal end (towards the body) of catheter 400. While in some embodiments, the orifice is aimed to be substantially perpendicular to a long axis of the catheter, in some embodiments, it is at various angles.
- the angle is not fixed and is varied, for example, by manipulating (e.g., axially, radially and/or rotationally) an inner tube which encloses lumen 412 attached to the orifice
- the width of orifice 416 is about 0.5 mm.
- the width is larger than about 0.5 mm such as about 0.6 mm or about 0.7 mm.
- the width is smaller than about 0.5 mm such as about 0.4 mm or about 0.3mm or about 0.2 mm.
- the width of catheter 400 is about 1 mm.
- the width is less than about 1 mm, such as about 0.3mm or about 0.5 mm or about 0.6 mm or about 0.8mm.
- the width is larger than about 1 mm, such as about 1.2 mm or about 1.5 mm.
- the distance of orifice 416 from the distal end of catheter 400 is about 1 mm.
- the distance is larger than about 1 mm, such as about 1.5 mm or about 2 mm or about 3 mm.
- the distance is smaller than about 1 mm.
- catheter 400 comprises a cover 424 closing lumen 412 at the distal end of catheter 400.
- cover 424 forms, at least partially, an integral part of tube 410.
- a guide- wire 414 is inserted in lumen 412, reaching orifice 416.
- guide-wire 414 is soft and/or flexible, at least at the distal section, enabling guide- wire 414 to enter orifice 416.
- guide- wire 414 is bent at the distal end, further enabling guide- wire 414 to enter orifice 416.
- guide-wire 414 is fabricated as a part of catheter 400, where guide- wire 414 is, optionally, removable from catheter 400.
- catheter 400 comprises at least one expandable element 418 around a section at the distal end of catheter 400, with one element 418 having an orifice aligned with orifice 416.
- two or more elements 418 are expandable to form a passage in front of orifice 416.
- expandable element 418 is configured to press against the walls of the vesicular vein 420 so as to block leakage of a sclerosant beyond the opening of the deferential vein 422, upstream and/or downstream.
- expandable element 418 comprises an inflatable balloon, optionally with a lumen 426 inside tube 410 (or wall thereof) for inflating and deflating balloon element 418.
- catheter 400 was maneuvered into vesicular vein 420 (1 12) near the opening of differential vein 422 (110), and that the expandable element 418 is an inflatable balloon.
- An exemplary method of maneuvering a catheter to reach an opening of the deferential vein is described later on.
- an operation of catheter 400 comprises:
- guide-wire 414 is removed before injecting the sclerosant agent.
- an internal catheter is moved inside catheter 400 along guide-wire 414 for injecting the sclerosant agent.
- a blocking element such as foam plug is injected instead of a sclerosant.
- inflated balloon 418 holds catheter 400 in place such that orifice 416 is facing and attaching to the opening of the deferential vein wherein the inflated balloon blocks the sclerosant from reaching vesicular vein 420 and unfavorably occluding it.
- Fig. 4C schematically illustrates an orifice 416 at a distal end of the catheter 400, comprising radio opaque elements 428 around and/or near the orifice, enabling to position the orifice at an opening of a branching vein, in accordance with some embodiments of the invention.
- Other configurations may be used as well.
- orifice 416 of catheter 400 is aligned with the opening of deferential vein 422 using the asymmetric arrangement of one or more radio-opaque elements 428 about orifice 416.
- the asymmetric arrangement of radio-opaque elements 428 enables to distinguish when orifice 416 is facing the opening of the vein or orifice 416 is opposite the opening.
- elements 418 are used in conjunction with guide-wire 414, to allow faster and/or easier initial positioning.
- an operation of catheter 400 comprises:
- a region about the perimeter of orifice 416 is coated with an adhesive material adapted for temporary contact with the vesicular vein 420.
- the material becomes adhesive responsive to a temperature change (e.g., provision of hot water in catheter 400 or exit form a cool catheter) and/or material (e.g., in blood flow and/or provided in the catheter).
- the material becomes non-adhesive or dissolves responsive to a temperature and/or material.
- sol-gel compound e.g. similar to methyl cellulose
- the temperature and/or material are affected by flushing lumen 412 with a fluid.
- an operation of catheter 400 comprises: (a) guiding catheter 400 such that orifice 416 contacts about the opening of the deferential vein as described above.
- catheter 400 can be used to deploy a coil as described below with respect the apparatus of Fig. 5.
- catheter 400 is configured to access the deferential vein subcutaneously in a procedure similar to laparoscopy.
- deferential vein 110 or vesicular plexus 128, is occluded by a coil (or spring) deployed in the vein.
- the occlusion is carried out by the coil body and/or by thrombosis induced by the coil.
- the coil is contractible from a thin element such as a strip.
- the coil is deployed subcutaneously using procedure similar to laparoscopy.
- deferential vein 522 (110) is referred to as an example of a vein branching from another vein and vesicular vein 520 (112) is referred to as an example of a vein into which a branching vein opens.
- FIG. 5 A schematically illustrates an apparatus 500 for deploying a coil 510 (shown in a stretched state) in the deferential vein (or another branching vein), while Fig. 5B schematically illustrates apparatus 500 after the coil is deployed, in accordance with some embodiments of the invention.
- Apparatus 500 and coil 512 are configured and adapted to reach the small opening of the deferential vein of a width of about or less than about 0.5 mm (down to about 0.25mm or 0.2 mm), and to be inserted into the vein without inflicting damage to the delicate vas deferens that is attached to deferential vein 110.
- initially coil 510 is formed from a strip.
- the strip width is suitable and/or adapted for insertion at the vein opening and inwards into the vein.
- the strip width is smaller than the vein opening such that it can be maneuvered during the procedure of insertion into the vein.
- the width is about 0.25 mm.
- the width is larger such as about 0.3 mm, about 0.4 mm, about 0.5 mm, or an intermediate value.
- the width is less than about 0.25 mm, such as about 0.2 mm.
- coil 510 is made of a shape memory alloy (SMA) such as Nitinol (TM) .
- SMA shape memory alloy
- TM Nitinol
- coil 510 coils from a strip form responsive to temperature in the vein.
- coil 510 is coiled responsive to heat, for example, by inducing current with electromagnetic radiation.
- apparatus 500 comprises: (a) a wire (and/or tube) 512 adapted to maneuver to the opening of deferential vein 522;
- release mechanism 516 mounted on the distal end (towards the body) of wire 512.
- release mechanism 512 is mounted with coil 510, in the initial form of a strip, on the distal end of wire 512
- release mechanism 516 is controlled by a control wire or rod 514.
- apparatus 500 was maneuvered into vesicular vein 520 (112) near the opening of the differential vein 522 (110).
- the path for maneuvering an apparatus to reach an opening of the deferential vein is described later on.
- an operation of apparatus 500 comprises: (a) maneuvering coil 510 (in a strip form) to the opening of deferential vein 522; (b) inserting coil 510 into deferential vein 522; and
- scelrosant and/or adhesive are provided as well.
- apparatus 500 is maneuvered inside a catheter that optionally protects the vessels walls from damage by apparatus 500 and/or optionally facilitates the maneuvers in the veins, such as tube catheter with open distal and proximal ends.
- apparatus 500 is operated after the catheter is pulled back to enable the deployment of coil 510.
- the catheter is used to flush coil 510 and/or release mechanism 516 with liquid in a temperature adapted for maintaining coil 510 and/or release mechanism 516 in a particular form suitable for the operation.
- apparatus 500 and coil 510 are inserted in catheter 400.
- coil 510 in a strip form, is inserted via orifice 416 into the opening of deferential vein 522, where the guiding of catheter 400 as described above optionally helps in positioning the end of coil 512 in the strip form at the opening of deferential vein 522.
- the insertion is carried out when catheter 400 is coupled to vesicular vein 520 as described above with reference to Fig. 4.
- lumen 412 of catheter 400 is used to flush a fluid with a temperature suitable to affect the coiling of coil 510.
- release mechanism 516 is as known in the art of stent or other grafts deployments.
- coil 510 is held by a latch (e.g. a pin) that is released by pulling control wire 514.
- release mechanism comprises a shape memory element configured to release coil 510 and is released when subject to a suitable temperature, such as by flushing it with a fluid in an optional catheter around apparatus 500 and/or upon reaching body temperature.
- deferential vein 110 or vesicular plexus In some embodiments of the invention, deferential vein 110 or vesicular plexus
- 128 is occluded by a procedure and equipment similar to laparoscopy and performed from outside the blood vessel.
- the occlusion comprises an electric coagulation applied to the external walls of the vein.
- the occlusion is effected by heat produced by electric current.
- the coagulation is effected by hot fluid.
- the coagulation is effected by cold fluid.
- deferential vein 110 is attached to the vas deferens, both being delicate vessels, in the order of sub-millimeter width, such as about 0.2 to about 0.5 mm, and typically vesicular plexus 128 has a plurality of branches.
- each branch of the plurality of branches of vesicular plexus 128 is optionally separated from the surrounding tissues.
- an apparatus is provided which performs a combined separation and occlusion.
- coagulating energy is provided from outside the vein, on opposite side from sensitive tissue.
- deferential vein 610 (110) is referred to as an example of a vein branching from another vein and vesicular vein 112 is referred to as an example of a vein into which a branching vein opens, whereas the a vas deferens 612 represents also tissues around the vesicular plexus.
- 'spike' denotes an elongated apparatus adapted to separate a vein from the surrounding tissues and to form a loop at one end around the vein.
- the term 'loop' denotes a closed loop or, optionally or alternatively, an arc optionally nearing a closed loop form, such as about 270° or more such as about 300° or about 360° or more.
- a partial loop for example, of 90°, 120°, 150° or intermediate or greater angle may be used.
- Fig. 6 A schematically illustrates a section of deferential 610 vein (110) and a section of vas deferens 612 as they are attached to each other.
- Fig. 6B schematically illustrates a spike 614 inserted between the deferential vein and the vas deferens, in accordance with some embodiments of the invention.
- spike 614 is introduced through the skin of the frontal pelvis into the abdomen in a procedure similar to laparoscopy, and inserted between deferential vein 610 and vas deferens 612.
- spike 614 is curved at the distal end (towards the abdomen) so that it bends about the deferential vein 610.
- spike 614 is flexible, at least at the distal end, to facilitate maneuvering in the abdomen and to bend about the deferential vein 610.
- a tube e.g. a catheter adapted to penetrate the abdomen is used as an auxiliary tool for the spike such that the tube is maneuvered to a location proximal to the deferential vein, and spike 614 is inserted in the lumen of the tube to reach the deferential vein.
- the tube is removed before the separation or occlusion of the deferential vein, or optionally after the separation or occlusion of the deferential vein.
- spike 614 is curled around deferential vein 610, it is pulled in order to separate the deferential vein 610 from vas deferens 612.
- Fig. 6C schematically illustrates spike 614 separating deferential vein 610 from vas deferens 614, in accordance with some embodiments of the invention.
- spike 614 is configured to curl, so that it forms a loop around deferential vein 610, without touching vas deferens 614.
- Fig. 6D schematically illustrates spike 614 curling into a loop around deferential vein 610 separated from vas deferens 614, in accordance with some embodiments of the invention.
- spike 614 comprises a tube 614, optionally flexible at least about the distal section that is adapted to curl and loop.
- the section length is about 3 mm to about 15 mm, according to the operation procedure and vein.
- the section width is about 1 mm. optionally the width is less than about 1 mm, such as about 0.5 mm. Optionally, the section width is larger than about 1 mm, such as about 1.2 or about 1.5 mm.
- tube 614 has a tapered tip at one end (as illustrated for example by 628 in Fig. 6E) which is adapted to separate at least a part of the deferential vein 610 from the vas deferens.
- spike 614 comprises or is coated with a material for smooth movement in the abdomen and/or for avoiding damage to organs, and particularly, without limiting, avoiding damage to the delicate deferential vein and vas deferens.
- spike 614 comprises:
- Fig. 6E schematically illustrates a spike 614 having lumen 618 with control wire 620, in accordance with some embodiments of the invention.
- spike 614 is configured to curl by manipulating control wire 620 in lumen 618 from the proximal end.
- control wire 620 is attached alongside spike 614.
- spike 614 with lumen 618 comprises a shape memory alloy so that by flushing lumen 618 with a fluid in a suitable temperature spike 614 curls.
- by adjusting the temperature the curvature is controlled.
- spike 614 comprises a bi-metal construction at the distal end so that by flushing lumen 618 with a fluid in controlled temperature the curvature is controlled.
- a control wire 620 is used for maneuvering in the abdomen, and another control wire 620 is used to separate and/or loop spike 614.
- another control wire 620 is used for looping the spike 614.
- the control wires or other wires may be used for the reverse operation for opening the loop and removing spike 614.
- Fig. 6E further illustrates schematically spike 614 having lumen 618 with a filament 624 at the distal end connected to conductors 620, in accordance with some embodiments of the invention.
- the conductors exit at the proximal end and can be connected to a current source.
- spike 614 when spike 614 is looped (curled) around deferential vein 610, current is supplied via conductors 620 to filament 622 which heats up and coagulates deferential vein 610.
- the current is supplied in a short burst or pulse such that deferential vein 610 is coagulated but the vein environment is not heated, at least avoiding a detrimental effect on other organs, particularly vas deferens 612.
- filament 622 and conductors 624 are eliminated, and spike 614 is adapted for high temperature sufficient to occlude the deferential vein.
- lumen 622 is configured to fill with high temperature fluid so that that deferential vein 610 is occluded by thermally induced thrombosis.
- a separate tube is inserted in lumen 622 and filled with hot fluid to apply the thermal occlusion.
- the spike 614 is adapted for low temperature such as that of liquid air or similar temperature, and filament 622 and conductors 624 are eliminated.
- lumen 622 is configured to fill with low temperature fluid so that that the deferential vein 610 is occluded by cryogenic (freezing) induced thrombosis.
- a separate tube is inserted in lumen 622 and filled with cold fluid to apply the cryogenic (hypothermal) occlusion.
- the spike is pre-configured to curl and prevented form doing so by an inner stylet or an outer over tube. Retracting the outer over tube and/or stylet, allows spike 614 to curl.
- spike 614 is curled by inserting a culling stylet into a lumen thereof.
- a top of spike 614 is more flexible than a body thereof, so that the curling stylet can only cause curling at the tip.
- the coagulation procedure as described above is performed with imaging control.
- the visual control is by x-ray imaging.
- spike 614 comprises radio-opaque elements so that it is distinguished under x-ray imaging.
- the operation is guided by ultra sound imaging, for example by using a TRUS (Trans-rectal Ultrasound) probe.
- TRUS Trans-rectal Ultrasound
- a fiber-optic tube is inserted into the abdomen in a laparoscopic procedure near spike 614, illuminating spike 614 and nearby organs, including deferential vein 610 and vas deferens 612, and the operation is controlled from a monitor.
- spike 614 is colored such that is clearly distinguished relative to the environment.
- deferential vein 110 is occluded by injecting a sclerosant agent into the vein in a in a procedure similar to laparoscopy.
- deferential vein 110 or a branch of vesicular plexus 128 is held by a gripper (e.g., a pair of arms shaped for gripping a vessel) mounted on a tube and an injector is inserted in the tube to pierce deferential vein 110 and inject a sclerosant.
- a gripper e.g., a pair of arms shaped for gripping a vessel
- the vein in order to occlude deferential vein 110, the vein is optionally separated from the vas deferens in order not to damage the latter.
- each branch of the plurality of branches of vesicular plexus 128 is optionally separated from the surrounding tissues.
- an appropriate apparatus is adapted to perform a combination of separation and occlusion.
- the vein is secured so that an injector can safely penetrate the delicate vein without damaging other tissues or organs.
- the equipment is configured to separate the vein, grip the vein, and provide a path to the vein from outside the abdomen.
- deferential vein 720 (110) is referred to as an example of a vein branching from another vein and the vesicular vein is referred to as an example of a vein into which a branching vein opens, whereas the vas deferens represents also other tissues around the vesicular plexus.
- Fig. 7 A schematically illustrates a tube 710 having a lumen 718 and a hinged pair of grippers 712 at the distal end (towards the vein), shown in open position, in accordance with some embodiments of the invention.
- grippers 712 have a rounded shape, optionally tapered at the distal end such as to enable separation of the deferential vein from other tissues.
- shape of grippers 712 on the side facing one another is rounded or shaped such as to grip a vein firmly but without destroying or damaging the vein in a manner which that would prevent the vein occlusion and/or cause hemorrhage.
- grippers 712 comprise or are coated with a slippery material for supporting movement in the abdomen and/or for avoiding damage to organs, and particularly, without limiting, avoiding damage to the delicate deferential vein and vas deferens.
- the gripers define a space between them for holding a vein.
- the width of gripper 712 is adapted to insert between the deferential vein and connecting tissues such as the vas deferens. Accordingly, in some embodiments of the invention, the maximal width of gripper 712 is about 1 mm. Optionally, the maximal width of gripper 712 is larger then about 1 mm, such as about 1.5 mm. Optionally, the maximal width is smaller than about 1 mm such about as 0.8 mm.
- the length of gripper 712 is adapted to separate and grip the deferential vein. Accordingly, the length of gripper 712 is about 1 mm. Optionally, the length is larger than about 1 mm, such as about 1.5 mm or about 2 mm. Optionally, the length is smaller than about 1 mm, such as about 0.8 mm.
- the maximal width of the opening between grippers 712 in a closed configuration is adapted to grab a vein. Accordingly, in some embodiments of the invention, the maximal width of the opening is about 0.3 mm. Optionally, the maximal width less than about 0.3 mm such as about 0.2 mm. Optionally, the maximal width is larger than about 0.3 mm such as about 0.4 mm or about 0.5 mm.
- 'gripper' denotes in the discussion, according to the context, a pair of grippers and optionally tube 710 with the mounted grippers 712.
- the procedure is controlled by the imaging methods described above.
- the gripper is inserted in a closed state, and opens to grab the vein and closes on it.
- gripper 712 is controlled by a control wire 714 inserted in lumen 718.
- control wire 714 is installed in lumen 718 before the gripper is introduced into the abdomen.
- control wire 714 is inserted in lumen 718 after the introduction of tube 710 into the abdomen and attaches to gripper 712 at near the distal end.
- control wire is combined with tube 712 outside lumen 718, such as alongside tube 718.
- pulling control wire 714 from the proximal end closes the gripper.
- gripper 712 is closed by pushing control wire 714, or otherwise maneuvering the wire, such as by rotating the wire or with a handles that control the position of grippers 712 similar to scissors.
- tube 710 is introduced into the abdomen and inserted, typically with one gripper 712, between the deferential vein 720 and the vas deferens (see also Fig 6A. to Fig. 6D) and grips vein 720.
- Fig. 7B schematically illustrates tube 710 having lumen 718 and comprising hinged pair of grippers 712 shown in closed position around vein 720 at the distal end, in accordance with some embodiments of the invention.
- Fig. 7C schematically illustrates tube 710 having lumen 718 and comprising hinged pair grippers 712 shown in a closed around vein 720 position at the distal end, and an injector 716 inserted in lumen 718 piercing vein 720, in accordance with some embodiments of the invention (guide wire 714 is not shown for clarity).
- injector 716 comprises a tube having a lumen wherein tube 716 comprises a pointed tip having an orifice.
- the injector comprises a stopper, such as a ring near the tip, configured to prevent the injector from piercing through the vein.
- the stopper is about 0.1 mm from the tip.
- the stopper is about 0.2 mm from the tip.
- the stopper is about 0.3 mm from the tip.
- gripper 712 when gripper 712 holds vein 720, gripper
- injector 716 is inserted into lumen 718 and pushed against gripped vein 720, piercing into the vein.
- a sclerosant agent is injected into vein 720 via injector 716.
- injector 716 is pulled out of lumen 718. Subsequently, gripper 712 is opened, optionally by pushing or otherwise maneuvering control wire 714, such as by rotating the wire, releasing vein 720. Tube 710 and gripper 712 are pulled out of the abdomen, optionally in closed state. Optionally, injector 716 is pulled out with tube 710.
- both vessels may be closed and/or occluded, particularly in life threatening condition such as a developed prostate cancer and/or metastases.
- life threatening condition such as a developed prostate cancer and/or metastases.
- the subject is in an age where fertility is not important closing both the deferential vein and the vas deferens may be performed, particularly if the separation between them is difficult.
- closing the deferential vein and the vas deferens is carried out, at least partly, using procedures as described above.
- the subcutaneous approach (similar to laparoscopy) is performed via the abdomen wall, optionally near the groin or loins.
- the approach is via a testis sack in an upward direction.
- the procedure is performed using a coaxial system, with a femoral vein sheath, two shaped guiding catheters, one for the left side and a different curve for the right, both designed to match the expected anatomy.
- the procedure is performed with a 6 French sheath and 6 French guiding catheters through which the 3 French treatment catheter is placed.
- the entire procedure is performed using a 3 F infusion catheter with tandem balloons (a proximal and distal balloon) or a single proximal balloon 20-25 cm from its tip, and relying on the patient's compressing the vein in the groin.
- the 3 French catheter maneuvered over a stiff 0.014-0.018" wire with a variably curved, soft, flexible tip that could be used to directly engage the orifice of the ISV.
- a procedure in accordance with an exemplary embodiment of the invention is performed as follows:
- the localization of the right femoral vein puncture site is confirmed by physical examination — e.g., at or below a line from the anterior superior iliac spine to the symphysis pubis.
- the vein is punctured with an 18 g femoral puncture needle.
- the needle is sheathed.
- a venous puncture is first performed as a two wall puncture to allow an additional 1 ml local anesthesia to be placed deep into the vein.
- the guidewire is brought through the needle into the vein and advanced into the pelvis.
- the needle or sheath is withdrawn around the guidewire while compressing the puncture site.
- the venous sheath is placed over the guidewire with its external port at the groin.
- the side port of the sheath is optionally flushed with heparinized saline solution, and this is optionally repeated throughout the procedure at 5-10 minutes intervals.
- the guiding catheter is advanced into the inferior vena cava (IVC) over the guidewire, and, under fluoroscopic control, maneuvered into the orifice of the left renal vein.
- IVC inferior vena cava
- the junction of the left renal vein with the IVC is an obtuse angle, heading caudally or cephalad from the kidney, and then the internal spermatic vein (ISV) orifice joins the left renal vein at an acute angle, making it difficult to enter from the upwards slanting renal vein.
- ISV internal spermatic vein
- the ISV joins the renal vein together with or just below a paraaortic vein, and there may be difficulty in recognizing this situation, and identifying the orifice of the ISV.
- the guiding catheter is maneuvered so that its tip overlies the orifice and, optionally, with gentle but firm rotation of the catheter, the orifice of the ISV is engaged.
- the latter operation is aided by a combination of suspended respiration and tilting of the fluoroscopic table.
- a guiding catheter with an alternative tip may be needed to engage the orifice of the ISV.
- the orifice of the left ISV When the orifice of the left ISV is first encountered, it may have an orifice valve which is open or closed.
- the valve can usually be entered by tilting the patient head down and attempting to advance the inner (coaxial) 3F (I mm) inner infusion catheter. After entering the orifice of the ISV with the 3 F infusion catheter, there may be additional valves all along the ISV which may be difficult to pass.
- the valves are optionally passed by a combination of patient/table positioning, breathing maneuvers, and applied suction via the guiding catheter.
- a balloon tipped catheter placed at the orifice to which suction is applied may be helpful in opening the valve and allowing the treatment catheter to cross it, by distending the vein.
- a 3F infusion catheter optionally with occlusion balloon(s) is introduced with the .014 in guidewire in place.
- the treatment catheter is optionally maneuvered to the lowest desired point for sclerotherapy - optionally just above the inguinal ligament.
- intravenous contrast is injected into the catheter through the central port hub under fluoroscopic control and images are obtained of the ISV, both distally and proximally, using appropriate manipulation of the tilting fluoroscopy table to establish the anatomy of the ISV and its communicating and collateral tributaries.
- Radiology imaging is used to identify both collateral ISV tributaries as well as intercommunications between the ISV and other retroperitoneal veins, and whether there are evident communications to other significant veins, such as the renal capsular vein, the ureteral vein and paravertebral retroperitoneal veins.
- the sclerotherapy treatment optionally covers the length of the ISV from just above the inguinal ligament until within 3-5 cm of the ISV orifice.
- the treatment comprises segmental injection of sclerosant while the ISV is compressed in the inguinal region to prevent reflux of sclerosant downwards and flushing out of the sclerosant upwards with the venous blood flow.
- a mixture of up to 2 ml sclerosing agent with 0.25-0.5 ml 2% local anesthesia, such as lidocaine, is optionally made and agitated in a 3-5 ml plastic syringe. It may be transferred from syringe to syringe using a stopcock arrangement to produce foam.
- the amount of sclerosant agent depends on the size of the ISV. If the treatment catheter has a distal balloon, it is optionally gently inflated to occlude the vein. Other occluding means may be used as well. Occlusion is optionally confirmed by a small amount of intravenous contrast being injected through the side hole of the treatment catheter.
- intravenous contrast material when there is a proximal balloon on the treatment catheter (or on the end of the guiding catheter) it is gently inflated to occlude the upper portion of the ISV.
- Repeated control injection of intravenous contrast is optionally provided until there is no reflux of contrast material into the veins below the inguinal region (e.g., towards the scrotum) indicating thorough occlusion of the ISV continuation into the scrotum.
- a small syringe with 0.5-1.0 ml intravenous contrast material is prepared. Half is injected into the treatment catheter. It is observed under fluoroscopy to make sure that it does not continue below the inguinal region towards the scrotum.
- the occlusion balloon (if present) is repositioned/re-inflated or digital compression of the groin is adjusted until there is no contrast which passes the inguinal region. Then, about 1-2 ml of the sclerosant mixture is injected. The tip of the treatment catheter is withdrawn 10-15 cm, and the injected material is allowed to remain in the vein.
- the fluoroscopy table can be tilted slightly, "feet down", up to 10 degrees, but usually after the injection and the 5-10 minutes afterwards the table is kept in horizontal position.
- tilting is used to control a flow direction of sclerosing or other occlusion enhancing or causing material.
- the contents of the treated vein are aspirated through the catheter and discarded.
- the catheter is flushed with a small amount of saline or intravenous contrast.
- the ISV is optionally examined using intravenous contrast material with the patient in the semi-erect position (20-50 degrees) to confirm vein occlusion and identify any collateral veins which appear following occlusion of the main ISV.
- a second segment of vein is treated in the same manner, until only a 5 cm "stump" of the ISV remains visible as including contrast material inflow. If the ISV is adequately occluded, the guiding catheter is optionally flushed with sterile saline solution, and a semi-erect contrast injection is made into the left renal vein to help search for any collateral veins that fill the ISV that may not have been visible before the main ISV had been occluded.
- the same guiding catheter used for the left side is maneuvered to the right renal vein (Rt RV) and a diagnostic venogram is performed in the semi-erect position with a hand injection, looking for the number of right renal veins and their connections to the IVC, as well as for a variant Rt ISV configuration which joins one of the right renal veins directly instead of the ISV (usually the ISV will enter the IVC at the level of L2, though with 10-20 percent, there may be multiple connections between the Rt ISV and the IVC.
- RV right renal vein
- the left sided guiding catheter is optionally exchanged for the right sided guiding catheter whose tip is re-configured inside the IVC and brought to lie above the expected orifice of the Rt ISV.
- the inner catheter needs to be advanced into the right ISV. Similar to the left side operation, there may be valves that need to be crossed, using the same maneuvers and/or devices as described on the left. The remainder of the treatment is performed in the same fashion as on the left.
- the tandem catheter is withdrawn, the guiding catheter is pushed upwards to dislodge it from the Rt ISV orifice, turned and straightened by either maneuvering the tip into the left renal vein or downwards into the orifice of the left internal iliac vein, the guiding catheter is removed, the femoral vein sheath is removed and the puncture site is compressed for 5 minutes before allowing the patient to careful sit up while compressing the groin and begin his recovery.
- a direct venous puncture with an approach identical to PICC line insertion is used.
- a 100-120 cm long 4 French catheter shaped like a "Head Hunter” catheter with a hydrophilic tip is inserted either directly into the vein or through a 4F sheath.
- a single type of catheter is used to enter right and left sides.
- a flexible guidewire, possibly with hydrophilic coating and/or an "extra-soft" tip (like a "Bentson” wire) is used to advance the 4F catheter into the right ISV for sclerotherapy.
- a coaxial system is used and the guiding catheter comprises an inflatable balloon to permit occlusion of the upper orifice while the sclerosant is injected through the inner sclerotherapy catheter.
- the method does not use the coaxial system, and the treatment catheter comprises an occlusion balloon about 20-25 cm above the catheter tip to occlude the lumen of the ISV, and a second occlusion balloon in the distal portion of the sclerotherapy catheter.
- the sclerosant is injected via a side hole in the portion of the treatment catheter between the two balloons (in case of two balloons), or 3-5 cm from its distal end.
- the left side is treated using the same shaped guiding catheter to access the left ISV and catheterize it as described above for the femoral vein approach.
- a puncture performed in the right internal jugular in the usual fashion with local anesthesia with or without ultrasound guidance.
- a 4 or 5 French sheath is placed in the internal jugular vein, and the continuation of the procedure is performed in the same manner as the arm vein approach described above.
- the deferential vein 110 connects at one side to pampiniform plexus 118 and at the other side to vesicular vein 112.
- Vesicular plexus 128 connects prostate 120 to vesicular vein 114. In some cases vesicular plexus 128 has a plurality of branches connecting to vesicular vein 112.
- an approach is provided to reach the junction of deferential vein 1 10 and pampiniform plexus 1 18, for example, one or more of: Femoral vein approach
- the inferior vena cava is accessed via the femoral vein or arm vein or jugular vein as described above.
- Inferior vena cava to right internal spermatic vein, to the pampiniform plexus, reaching the opening of the deferential vein.
- the inferior vena cava is accessed via the femoral vein or arm vein or jugular vein as described above.
- Study 1 45 patients who suffer from PCa for were randomly selected and checked for varicocele. The diagnosis was made by physical examination and contact thermography, using a flexible liquid crystal thermostrip (FertiPro ® by
- kit form optionally with instructions and/or materials for treatment and/or vessel plugs.
- each of the verbs "comprise”, “include” and “have” as well as any conjugates thereof, are used to indicate that the object or objects of the verb are not necessarily a complete listing of members, components, elements or parts of the subject or subjects of the verb.
- the singular form “a”, “an” and “the” include plural references unless the context clearly dictates otherwise.
- the term “a procedure” or “at least one procedure” may include a plurality of compounds, including mixtures thereof.
- the term “treating” includes abrogating, substantially inhibiting, slowing and/or reversing the progression of a condition, substantially ameliorating clinical and/or aesthetical symptoms of a condition and/or substantially preventing and/or delaying the appearance of clinical and/or aesthetical symptoms of a condition.
- the word “exemplary” is used herein to mean “serving as an example, instance or illustration”. Any embodiment described as “exemplary” is not necessarily to be construed as preferred or advantageous over other embodiments and/or to exclude the incorporation of features from other embodiments.
- range format is merely for convenience and brevity and should not be construed as an inflexible limitation on the scope of the invention. Accordingly, the description of a range should be considered to have specifically disclosed all the possible subranges as well as individual numerical values within that range. For example, description of a range such as from 1 to 6 should be considered to have specifically disclosed subranges such as from 1 to 3, from 1 to 4, from 1 to 5, from 2 to 4, from 2 to 6, from 3 to 6 etc., as well as individual numbers within that range, for example, 1, 2, 3, 4, 5, and 6. This applies regardless of the breadth of the range.
Abstract
Description
Claims
Priority Applications (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US12/668,696 US20100286106A1 (en) | 2008-03-10 | 2008-07-13 | Methods and apparatus for treating the prostate |
CA2693227A CA2693227A1 (en) | 2007-07-13 | 2008-07-13 | Methods and apparatus for treating the prostate |
IL203271A IL203271A (en) | 2007-07-13 | 2010-01-12 | Apparatus for treating the prostate |
Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US11/826,283 US20090018486A1 (en) | 2007-07-13 | 2007-07-13 | Diagnosis and treatment of vericocele and prostate disorders |
US11/826,283 | 2007-07-13 | ||
US6451108P | 2008-03-10 | 2008-03-10 | |
US61/064,511 | 2008-03-10 |
Publications (2)
Publication Number | Publication Date |
---|---|
WO2009010964A2 true WO2009010964A2 (en) | 2009-01-22 |
WO2009010964A3 WO2009010964A3 (en) | 2010-02-25 |
Family
ID=40260179
Family Applications (3)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/IL2008/000973 WO2009010964A2 (en) | 2007-07-13 | 2008-07-13 | Methods and apparatus for treating the prostate |
PCT/IL2008/000972 WO2009010963A2 (en) | 2007-07-13 | 2008-07-13 | Methods and apparatuses for vascular and prostate treatment |
PCT/IL2008/000971 WO2009010962A2 (en) | 2007-07-13 | 2008-07-13 | Diagnosis and treatment of varicocele and prostate disorders |
Family Applications After (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/IL2008/000972 WO2009010963A2 (en) | 2007-07-13 | 2008-07-13 | Methods and apparatuses for vascular and prostate treatment |
PCT/IL2008/000971 WO2009010962A2 (en) | 2007-07-13 | 2008-07-13 | Diagnosis and treatment of varicocele and prostate disorders |
Country Status (6)
Country | Link |
---|---|
EP (2) | EP2178594A4 (en) |
JP (1) | JP2010533052A (en) |
CN (1) | CN101801289A (en) |
AU (2) | AU2008277251A1 (en) |
CA (3) | CA2693735A1 (en) |
WO (3) | WO2009010964A2 (en) |
Families Citing this family (22)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
TW200635566A (en) * | 2005-01-25 | 2006-10-16 | Vnus Med Tech Inc | Structures for permanent occlusion of a hollow anatomical structure |
CN103037929B (en) * | 2010-03-06 | 2015-08-26 | 新融合血管系统有限公司 | Reclaim catheter kit |
US9108029B2 (en) | 2012-05-21 | 2015-08-18 | Nfusion Vascular Systems, Llc | Recovery catheter assembly and method |
US9597205B2 (en) | 2012-06-06 | 2017-03-21 | Magenta Medical Ltd. | Prosthetic renal valve |
CN105473063B (en) | 2013-03-13 | 2019-03-08 | 马真塔医药有限公司 | Blood pumping and its manufacturing method |
US10583231B2 (en) | 2013-03-13 | 2020-03-10 | Magenta Medical Ltd. | Blood pump |
RU2525219C1 (en) * | 2013-04-02 | 2014-08-10 | Государственное бюджетное образовательное учреждение высшего профессионального образования "Тверская государственная медицинская академия" Министерства здравоохранения Российской Федерации | Method for retrograde sclerotherapy of varicocele in mesenteric-testicular anastomoses |
US9764113B2 (en) | 2013-12-11 | 2017-09-19 | Magenta Medical Ltd | Curved catheter |
JP2017500144A (en) * | 2013-12-27 | 2017-01-05 | レナルプロ・メディカル・インコーポレーテッドRenalpro Medical,Inc. | Device and method for the treatment of acute kidney injury |
RU2572553C1 (en) * | 2014-08-01 | 2016-01-20 | Леонид Зиновьевич Вельшер | Method of treating prostate cancer |
WO2016185473A1 (en) | 2015-05-18 | 2016-11-24 | Magenta Medical Ltd. | Blood pump |
WO2017040484A1 (en) * | 2015-08-31 | 2017-03-09 | Gentuity, Llc | Imaging system includes imaging probe and delivery devices |
US11039915B2 (en) | 2016-09-29 | 2021-06-22 | Magenta Medical Ltd. | Blood vessel tube |
EP3532120A1 (en) | 2016-10-25 | 2019-09-04 | Magenta Medical Ltd. | Ventricular assist device |
EP3544649B1 (en) | 2016-11-23 | 2023-06-07 | Magenta Medical Ltd. | Blood pumps |
JP7160935B2 (en) | 2017-11-28 | 2022-10-25 | ジェンテュイティ・リミテッド・ライアビリティ・カンパニー | Imaging system |
US10905808B2 (en) | 2018-01-10 | 2021-02-02 | Magenta Medical Ltd. | Drive cable for use with a blood pump |
CN115040777A (en) | 2018-01-10 | 2022-09-13 | 马真塔医药有限公司 | Ventricular assist device |
CN108158654B (en) * | 2018-01-12 | 2020-06-12 | 郑州大学第一附属医院 | Portable magnetic induction positioning and guiding device and method thereof |
US10893927B2 (en) | 2018-03-29 | 2021-01-19 | Magenta Medical Ltd. | Inferior vena cava blood-flow implant |
EP3749383B1 (en) | 2019-01-24 | 2021-04-28 | Magenta Medical Ltd. | Ventricular assist device |
RU2729431C1 (en) * | 2019-12-27 | 2020-08-06 | Федеральное государственное бюджетное образовательное учреждение высшего образования "Тихоокеанский государственный медицинский университет" Министерства здравоохранения Российской Федерации | Method of laparoscopic treatment of varicocele |
Citations (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5683411A (en) * | 1994-04-06 | 1997-11-04 | William Cook Europe A/S | Medical article for implantation into the vascular system of a patient |
US6384017B1 (en) * | 1995-12-15 | 2002-05-07 | Praecis Pharmaceuticals, Inc. | Methods for treating sex hormone-dependent conditions with Lhrh antagonists |
US20020165195A1 (en) * | 2001-05-01 | 2002-11-07 | Schering Corporation | Method of treating androgen-dependent disorders |
US20030208223A1 (en) * | 2000-03-23 | 2003-11-06 | Kleiner Daniel Eduard | Device incorporating a hollow element for being positioned along a body cavity of a patient and method of positioning the same |
US20040062750A1 (en) * | 1999-09-14 | 2004-04-01 | The General Hospital Corporation | Use of mullerian inhibiting substance for treating excess androgen states |
US20040267258A1 (en) * | 1997-09-11 | 2004-12-30 | Vnus Medical Technologies, Inc. | Expandable vein ligator catheter having multiple leads, and method |
US20050182342A1 (en) * | 2004-02-13 | 2005-08-18 | Medtronic, Inc. | Monitoring fluid flow in the gastrointestinal tract |
US20060052823A1 (en) * | 2004-08-31 | 2006-03-09 | Mirizzi Michael S | Apparatus, material compositions, and methods for permanent occlusion of a hollow anatomical structure |
Family Cites Families (28)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4714460A (en) * | 1983-07-29 | 1987-12-22 | Reynaldo Calderon | Methods and systems for retrograde perfusion in the body for curing it of the disease or immume deficiency |
CH668192A5 (en) * | 1985-11-29 | 1988-12-15 | Schneider Medintag Ag | CATHETER FOR TREATING NARROW BODIES, FOR EXAMPLE IN A BLOOD VESSEL. |
US4762128A (en) * | 1986-12-09 | 1988-08-09 | Advanced Surgical Intervention, Inc. | Method and apparatus for treating hypertrophy of the prostate gland |
AU4191989A (en) * | 1988-08-24 | 1990-03-23 | Marvin J. Slepian | Biodegradable polymeric endoluminal sealing |
FR2639237B1 (en) * | 1988-11-23 | 1997-10-31 | Boussignac Georges | CATHETER FOR INTRODUCTION INTO A BODY CHANNEL |
CN2086610U (en) * | 1991-03-05 | 1991-10-16 | 陆秉仁 | Double-bag prostatic urethreurynter |
US5529574A (en) * | 1992-08-21 | 1996-06-25 | Frackelton; James P. | Method and apparatus for treatment of the prostate |
US5779673A (en) * | 1995-06-26 | 1998-07-14 | Focal, Inc. | Devices and methods for application of intraluminal photopolymerized gels |
US5989230A (en) * | 1996-01-11 | 1999-11-23 | Essex Technology, Inc. | Rotate to advance catheterization system |
US5947985A (en) * | 1997-11-12 | 1999-09-07 | Imran; Mir A. | Apparatus and method for cleaning diseased vein grafts |
US6036689A (en) * | 1998-09-24 | 2000-03-14 | Tu; Lily Chen | Ablation device for treating atherosclerotic tissues |
US6319251B1 (en) * | 1998-09-24 | 2001-11-20 | Hosheng Tu | Medical device and methods for treating intravascular restenosis |
US6575932B1 (en) * | 1999-12-02 | 2003-06-10 | Ottawa Heart Institute | Adjustable multi-balloon local delivery device |
EP1241993B1 (en) * | 1999-12-22 | 2007-03-28 | Boston Scientific Limited | Endoluminal occlusion-irrigation catheter |
US20050107738A1 (en) * | 2000-07-21 | 2005-05-19 | Slater Charles R. | Occludable intravascular catheter for drug delivery and method of using the same |
GB2369996B (en) * | 2000-12-18 | 2004-06-23 | S T D Pharmaceutical Products | Method and apparatus for producing an injectable foam |
US7169161B2 (en) * | 2001-11-06 | 2007-01-30 | Possis Medical, Inc. | Guidewire having occlusive device and repeatably crimpable proximal end |
WO2003075993A1 (en) * | 2002-03-09 | 2003-09-18 | Brodersen Jens P | Sclerosing catheter for sclerosing blood vessels, especially veins |
US20040180855A1 (en) * | 2003-02-19 | 2004-09-16 | Schumacher William A. | Methods of treating thrombosis with reduced risk of increased bleeding times |
US7077801B2 (en) * | 2003-02-19 | 2006-07-18 | Corlife Gbr | Methods and devices for improving cardiac output |
DE502004009815D1 (en) * | 2003-10-29 | 2009-09-10 | Celon Ag Medical Instruments | Medical device for the electrotomy |
US7824408B2 (en) * | 2004-08-05 | 2010-11-02 | Tyco Healthcare Group, Lp | Methods and apparatus for coagulating and/or constricting hollow anatomical structures |
US20060079923A1 (en) * | 2004-08-09 | 2006-04-13 | Manik Chhabra | Aneurysm treatment using semi-compliant balloon |
JP2008509781A (en) * | 2004-08-19 | 2008-04-03 | ベインアールエックス,インコーポレイティド | Occlosable intravascular catheter for drug delivery and method of using the same |
US20060159767A1 (en) * | 2004-12-22 | 2006-07-20 | Elan Pharma International Limited | Nanoparticulate bicalutamide formulations |
TW200635566A (en) * | 2005-01-25 | 2006-10-16 | Vnus Med Tech Inc | Structures for permanent occlusion of a hollow anatomical structure |
JP2008173137A (en) * | 2005-03-03 | 2008-07-31 | Goodman Co Ltd | Double balloon catheter |
US20060204588A1 (en) * | 2005-03-10 | 2006-09-14 | Elan Pharma International Limited | Formulations of a nanoparticulate finasteride, dutasteride or tamsulosin hydrochloride, and mixtures thereof |
-
2008
- 2008-07-13 AU AU2008277251A patent/AU2008277251A1/en not_active Abandoned
- 2008-07-13 CN CN200880106666A patent/CN101801289A/en active Pending
- 2008-07-13 WO PCT/IL2008/000973 patent/WO2009010964A2/en active Application Filing
- 2008-07-13 EP EP08776606A patent/EP2178594A4/en not_active Withdrawn
- 2008-07-13 CA CA2693735A patent/CA2693735A1/en not_active Abandoned
- 2008-07-13 CA CA2693225A patent/CA2693225A1/en not_active Abandoned
- 2008-07-13 WO PCT/IL2008/000972 patent/WO2009010963A2/en active Application Filing
- 2008-07-13 WO PCT/IL2008/000971 patent/WO2009010962A2/en active Application Filing
- 2008-07-13 CA CA2693227A patent/CA2693227A1/en not_active Abandoned
- 2008-07-13 AU AU2008277252A patent/AU2008277252A1/en not_active Abandoned
- 2008-07-13 JP JP2010516646A patent/JP2010533052A/en active Pending
- 2008-07-13 EP EP08776607A patent/EP2170180A4/en not_active Withdrawn
Patent Citations (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5683411A (en) * | 1994-04-06 | 1997-11-04 | William Cook Europe A/S | Medical article for implantation into the vascular system of a patient |
US6384017B1 (en) * | 1995-12-15 | 2002-05-07 | Praecis Pharmaceuticals, Inc. | Methods for treating sex hormone-dependent conditions with Lhrh antagonists |
US20040267258A1 (en) * | 1997-09-11 | 2004-12-30 | Vnus Medical Technologies, Inc. | Expandable vein ligator catheter having multiple leads, and method |
US20040062750A1 (en) * | 1999-09-14 | 2004-04-01 | The General Hospital Corporation | Use of mullerian inhibiting substance for treating excess androgen states |
US20030208223A1 (en) * | 2000-03-23 | 2003-11-06 | Kleiner Daniel Eduard | Device incorporating a hollow element for being positioned along a body cavity of a patient and method of positioning the same |
US20020165195A1 (en) * | 2001-05-01 | 2002-11-07 | Schering Corporation | Method of treating androgen-dependent disorders |
US20050182342A1 (en) * | 2004-02-13 | 2005-08-18 | Medtronic, Inc. | Monitoring fluid flow in the gastrointestinal tract |
US20060052823A1 (en) * | 2004-08-31 | 2006-03-09 | Mirizzi Michael S | Apparatus, material compositions, and methods for permanent occlusion of a hollow anatomical structure |
Also Published As
Publication number | Publication date |
---|---|
WO2009010962A2 (en) | 2009-01-22 |
WO2009010963A2 (en) | 2009-01-22 |
EP2170180A2 (en) | 2010-04-07 |
CN101801289A (en) | 2010-08-11 |
AU2008277252A1 (en) | 2009-01-22 |
WO2009010964A3 (en) | 2010-02-25 |
AU2008277251A1 (en) | 2009-01-22 |
EP2178594A4 (en) | 2011-02-23 |
WO2009010963A3 (en) | 2010-01-14 |
CA2693227A1 (en) | 2009-01-22 |
JP2010533052A (en) | 2010-10-21 |
CA2693735A1 (en) | 2009-01-22 |
EP2170180A4 (en) | 2011-02-23 |
WO2009010962A3 (en) | 2010-09-16 |
CA2693225A1 (en) | 2009-01-22 |
EP2178594A2 (en) | 2010-04-28 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US20100286106A1 (en) | Methods and apparatus for treating the prostate | |
WO2009010964A2 (en) | Methods and apparatus for treating the prostate | |
US20090018486A1 (en) | Diagnosis and treatment of vericocele and prostate disorders | |
US10369044B2 (en) | Inhibition of platelet activation, aggregation and/or adhesion by hypothermia | |
US6695787B2 (en) | Prostate visualization device and methods of use | |
Ascher et al. | Duplex-guided balloon angioplasty and stenting for femoropopliteal arterial occlusive disease: an alternative in patients with renal insufficiency | |
US11071550B2 (en) | Methods and devices for treating pancreatitis | |
Thomson et al. | Reproductive system | |
US20220000897A1 (en) | Methods for treatment of post-surgery laxity of tendons and tendon repair | |
Wunsch et al. | The interventional therapy of varicoceles amongst children, adolescents and young men | |
US8257411B2 (en) | Method for treatment of varices | |
IL203271A (en) | Apparatus for treating the prostate | |
US20100204639A1 (en) | Diagnosis and treatment of varicocele and prostate disorders | |
Maydeo et al. | Endoscopic balloon sphincteroplasty for extraction of large radiolucent pancreatic duct stones (with videos) | |
Ehrlich et al. | Division of prostatic anterior fibromuscular stroma reduces urethral resistance in an ex vivo human prostate model | |
Pearl | Techniques of endoscopic retrograde cholangiopancreatography | |
Jair et al. | Current Surgical Treatment of Choledocholithiasis and use of T-tube drainage | |
Anttinen et al. | MP01-03 TRANSURETHRAL ULTRASOUND ABLATION FOR BENIGN PROSTATIC HYPERPLASIA: THREE-MONTH CLINICAL OUTCOMES OF A PHASE 1-2 STUDY | |
Baron | Benign and malignant colorectal strictures | |
Lv et al. | Titanium Clip-dental Floss Traction-assisting Endoscopy in Patients With Difficulty in Cannulation Into the Duodenal Peridiverticular Papilla | |
Mann et al. | The WATER Study: a Review | |
Moran | Anterior resection of the rectum | |
WO2021168003A2 (en) | Deflectable anchor balloon catheter for vascular procedures | |
Ansari | PROF. APUL GOEL | |
Rubinstein et al. | V1150: Robotic-Assisted Laparoscopic Retroperitoneal Pyeloplasty |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
121 | Ep: the epo has been informed by wipo that ep was designated in this application |
Ref document number: 08776608 Country of ref document: EP Kind code of ref document: A2 |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2693227 Country of ref document: CA Ref document number: 203271 Country of ref document: IL |
|
NENP | Non-entry into the national phase |
Ref country code: DE |
|
WWE | Wipo information: entry into national phase |
Ref document number: 12668696 Country of ref document: US |
|
122 | Ep: pct application non-entry in european phase |
Ref document number: 08776608 Country of ref document: EP Kind code of ref document: A2 |