WO2001026563A1 - Procede d'administration de medicament a un site d'acces adapte au trocart - Google Patents

Procede d'administration de medicament a un site d'acces adapte au trocart Download PDF

Info

Publication number
WO2001026563A1
WO2001026563A1 PCT/US2000/027902 US0027902W WO0126563A1 WO 2001026563 A1 WO2001026563 A1 WO 2001026563A1 US 0027902 W US0027902 W US 0027902W WO 0126563 A1 WO0126563 A1 WO 0126563A1
Authority
WO
WIPO (PCT)
Prior art keywords
port
site
sleeve
port site
expandable member
Prior art date
Application number
PCT/US2000/027902
Other languages
English (en)
Inventor
Marc D. Basson
Original Assignee
Yale University
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Yale University filed Critical Yale University
Publication of WO2001026563A1 publication Critical patent/WO2001026563A1/fr

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B17/00—Surgical instruments, devices or methods, e.g. tourniquets
    • A61B17/34—Trocars; Puncturing needles
    • A61B17/3417—Details of tips or shafts, e.g. grooves, expandable, bendable; Multiple coaxial sliding cannulas, e.g. for dilating
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B17/00—Surgical instruments, devices or methods, e.g. tourniquets
    • A61B17/34—Trocars; Puncturing needles
    • A61B17/3474—Insufflating needles, e.g. Veress needles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B90/00—Instruments, implements or accessories specially adapted for surgery or diagnosis and not covered by any of the groups A61B1/00 - A61B50/00, e.g. for luxation treatment or for protecting wound edges
    • A61B90/40—Apparatus fixed or close to patients specially adapted for providing an aseptic surgical environment

Definitions

  • This invention relates to the administration of medicaments for therapeutic purposes to a specific area of tissue, which is an entry site or a port site isolated from the body cavity in which a device, such as a trocar, has been inserted.
  • this invention relates to a method of inhibiting tumor cell adhesion in and around entry sites and particularly to those sites, generally referred to as port sites, which are used to gain entry into the abdominal cavity or other body cavities during minimally-invasive procedures, including thoracic and laparoscopic procedures, including surgeries, both exploratory and extractive, and including gasless procedures in addition to gas-assisted procedures, laparoscopic biopsy, and the administration of therapeutics via laparoscopic access to the abdominal cavity.
  • the invention also relates to a surgical device uniquely designed to inhibit tumor cell adhesion at the port sites or administer therapeutic agents to the port sites.
  • Port site recurrence occurs in humans and animal models. See the discussions in the following articles each of which is incorporated by reference thereto: Champault G. et al., "Port-site metastases. A prospective study_of 131 cases”. J Chir. 134:423-8,1997; Berends F. J. et al, "Subcutaneous metastases after laparoscopic colectomy", Lancet 344:58,1994; Wexner S. D.
  • the invention described herein is based on the discovery that tumor cell adhesion is pressure-responsive.
  • cation-dependent integrin-mediated adhesion such as via FA -related tyrosine phosphorylation , is suspected and the presence of serum potentiates this effect.
  • These critical observations and their impact on port site recurrence are not recognized in the literature. Thus the targeting of these mechanisms is also not evident from the literature.
  • the claimed invention is directed to methods and devices designed to inhibit tumor cell adhesion and consequently inhibit or prevent port site recurrence, by reducing pressure during laparoscopic surgery, washing serum from the port sites, or using chelators to block cation-dependent adhesion or compounds which directly inhibit cell adhesion.
  • This invention comprises minimally-invasive methods and apparatus useful for adding medicaments including those which will inhibit cell adhesion to an entry or port site.
  • medicaments include anesthetics, antibiotics, cytotoxic agents, including osmotic agents, growth factors and other cell-function-stimulants.
  • the present invention also provides a method of inhibiting attachment of tumor cells to an entry or port site comprising administering a composition capable of inhibiting or eliminating cell adhesion to a entry or port site, such as saline solution; antibodies to cell surface proteins; cell adhesion inhibitors; and, salts or chelators effective to inhibit integrin-mediated cell adhesion.
  • a composition capable of inhibiting or eliminating cell adhesion to a entry or port site such as saline solution; antibodies to cell surface proteins; cell adhesion inhibitors; and, salts or chelators effective to inhibit integrin-mediated cell adhesion.
  • the present invention also provides a method of evacuating fluids, both endogenous and previously administered fluids, including cell-containing fluids such as blood, from patient through an entry or port site.
  • the present invention is directed to the admimstration of medicaments through multiple port sites.
  • the present invention provides a method of inhibiting attachment of tumor cells to a port site or the peritoneal wall adj acent to a port site via employment of a trocar assembly which provides the following features, an expandable member, such as a balloon, of a sufficient size when inflated and disposed on the trocar assembly in such a way that when inflated or expanded the expandable member forms a protective barrier between the port site and the peritoneum; means of engaging the external skin above the port site in a manner which stabilizes the trocar and provides sufficient compression of the tissue at the port site so as to, in conjunction with the expandable member, isolate the port site from the abdominal cavity; and, at least one side port positioned in the wall of the trocar; and administering fluid materials capable of minimizing or eliminating cell adhesion through the at least one side port during the surgical procedure.
  • an expandable member such as a balloon
  • This invention further provides a trocar assembly which provides isolation of insertion sites from a body cavity when inserted into the body cavity which contains a sleeve having a distal end and a proximal end, wherein the distal end of the sleeve is adapted for insertion into the abdominal cavity, and the proximal end is open and is adapted for insertion of surgical instruments through the sleeve; and an expandable member positioned near the insertable end of the sleeve and of a size upon inflation such that a barrier is formed between the body cavity and the insertion site; and at least one side port coupled to the sleeve in communication with an opening near the distal end of the tubular member but proximal to the expandable member, the side port being adapted for administering fluids to the port site.
  • the disclosed trocar assemblies of this invention include those which further comprising engaging means which abut the external skin above the port site in a manner which stabilizes the trocar and provides sufficient compression of the tissue at the port site so as to, in conjunction with the expandable member, isolate the port site from the abdominal cavity.
  • the engaging means comprises a clip slidably mounted on the sleeve for securing the sleeve to the insertion site.
  • the invention disclosed herein further provides a trocar assembly which contains a side port coupled to the sleeve that is a valved gas inlet and an additional side port coupled to the sleeve that is adapted for aspirating materials from the body.
  • the invention further provides a trocar device in which the sleeve of the trocar has an outer tubular member and an inner tubular member, wherein the inner tubular member is located inside of, and is concentrically aligned with, the outer tubular member, and wherein the space between the outer and inner tubular members forms a passage for the transfer of gases or liquids.
  • the sleeve of the trocar has an outer tubular member and an inner tubular member, wherein the inner tubular member is located inside of, and is concentrically aligned with, the outer tubular member, and wherein the space between the outer and inner tubular members forms a passage for the transfer of gases or liquids.
  • Laparoscopic colectomy procedures provide multiple advantages for patients compared to open wound surgery. Patients experience less pain, less post-operative pulmonary compromise, less immune depression, less ileus and typically a shorter period when hospitalization is necessary. To summarize, patients experience less pain and a faster return to their pre-operative life style.
  • Tumors may spread by direct invasion, by vascular or lymphatic channels, or by intra-abdominal dissemination to mesentery, peritoneum, or the abdominal wall during surgery. Each process except for invasion requires viable non-adherent tumor cells to re- adhere to a new extracellular matrix. Not all tumor cells adhere, particularly within the peritoneum, and both local tissue factors and the adhesiveness of the tumor may influence initial adhesion. After adhesion, proliferation, angiogenesis, and invasion must outstrip immune surveillance for a clinically evident tumor to develop, but adhesion is a critical first step.
  • tumor handling during open surgery may be rougher than some minimally-invasive procedures, such as laparoscopic manipulation.
  • some minimally-invasive procedures such as laparoscopic manipulation.
  • the hypothesis that physical forces activate tumor cell adhesion neither implies that port site recurrence is more common than wound implantation after open surgery nor would be invalidated if port site recurrence were not more common.
  • open wound implantation, port site recurrence, and tumor dissemination in either laparoscopic or open surgery might be further reduced by minimizing forces applied to the tumor or by targeting the mechanisms of pressure-stimulated adhesion, regardless of the relative frequency of wound implantation in laparoscopic and open surgery.
  • Increased intraperitoneal pressure during laparoscopic procedures stimulates adhesion of shed intraperitoneal tumor cells and thus potentiates port site recurrence.
  • SW620 adhesion to Matrigel was pressure-responsive, exhibiting a 16.3 ⁇ 2.1% increase at 10 mmHg above ambient, and a 50.5 ⁇ 3.3% increase at 15 mm Hg. (*p ⁇ 0.002). Pressure also stimulated adhesion during gassing with filtered nitrogen.
  • SW620 adhesiveness was substantially decreased in the absence of serum. Nevertheless, increased pressure stimulated adhesion even in studies performed in a balanced electrolyte solution (phosphate buffered saline supplemented with 1 mM MgCl 2 and 1 mM CaCl ) without serum (p ⁇ 0.005). This increased adhesion was blocked by chelation (1 mM EOT A, 1 mM EGTA) and did not occur in phosphate buffered saline without calcium or magnesium, suggesting integrin and cation-dependence.
  • Pressure- stimulated adhesion was accompanied by tyrosine phosphorylation of intracellular proteins and phosphorylation (activation) of the integrin-associated Focal Adhesion [tyrosine] Kinase even when studies were performed in dishes to which the cells cannot adhere.
  • Pressure-stimulated adhesion was blocked by a functional antibody to the ⁇ l integrin subunit (1 ug/ml), by the p38 inhibitor SB203580 (50 ug) and by the tyrosine kinase inhibitors genistein (75 ug/ml) tyrphostin (50 mM) and erbstatin (10 uM). No effect on pressure-stimulated adhesion was observed upon the addition of the tyrosine kinase inhibitor PMSO vehicle without tyrosine kinase inhibitor addition.
  • the invention provides a means to inhibit cell adhesion, whether pressure-induced or integrin-mediated, by the admimstration of any fluid material.
  • the fluid material may be a saline solution used to wash cells away from the isolated port site or the material may act upon the cells to directly inhibit cell adhesion, and could be selected from materials such as antibodies to cell surface proteins, cell adhesion inhibitors, and salts or chelators effective to inhibit integrin-mediated cell adhesion.
  • a trocar assembly One type of medical device that can be used for these procedures is a trocar assembly.
  • the sleeve can be formed from an outer tubular member having a handle at its proximal end and an expandable member at or near its distal end.
  • the expandable member may be a balloon.
  • the device also comprises a means of engaging the external skin above the port site in a manner which stabilizes the trocar and provides sufficient compression of the tissue at the port site so as to, in conjunction with the expandable member, isolate the port site from the abdominal cavity.
  • This external engaging means can be situated on the anterior aspect of the abdominal wall.
  • This external engaging means can be in the form of a clip that is slidably coupled circumferentially along the outside of the outer tubular member. Such a clip is capable of being selectively slid and fixed along various points on the outer tubular member.
  • An alternative design would be a hinged circular clip with can either be a fixed part of the device or detachable from the device that would be fastened around the trocar at a position externally juxtaposed to the insertion site. Alternatively, continuous upward traction or other similar technique can be applied to the engaging means.
  • a penetrating member can be inserted through the handle of the sleeve so that it lies fairly concentrically along the length of the outer tubular member.
  • the penetrating member may be an elongated cylindrical structure having either a hollow or solid length.
  • a handle At the proximal end of the penetrating member, like the sleeve, is a handle, and when the penetrating member is fully inserted into the sleeve, the handle of the penetrating member lies proximal to the sleeve's handle.
  • the distal end of the penetrating member is sharp, and could be a blade, needle, or other similar structure.
  • the sharp distal end of the penetrating member lies distally to the distal end of the sleeve.
  • the penetrating member is able to pierce tissue, enabling the trocar assembly to be inserted into body cavities.
  • a blunt port device can be surgically inserted.
  • the sleeve also has a series of ports to facilitate the entry and removal of instruments, gases, and liquids.
  • the proximal end of the handle of the sleeve has a port for receiving the penetrating member and other surgical instruments.
  • various ports are located on the side or sides of the outer sleeve, either at the outer tubular member or handle of the sleeve.
  • One side port can be in communication with the expandable member, such that air, saline solution, or other suitable substances can enter and exit the port to expand and deflate the expandable member.
  • a mechanical means for expanding and deflating the expandable member such as one with an umbrella style mechanism.
  • Another side port can be adapted to receive fluids.
  • a passage leads from this side port towards the distal end of the sleeve such that fluids can enter and exit the sleeve from openings at or near the sleeve's distal end, but proximal to the expandable member, whereby the fluids are released into the port site rather than into the body cavity.
  • Two additional side ports having passages leading towards the distal end of the sleeve can also be present.
  • One can be adapted to allow for the aspiration of liquids, including endogenous and administered fluids, such as serum, blood, other cell- containing fluids and, if desired fluids which have been administered.
  • These side ports can have either single or multiple exits from the fluid input and fluid aspiration ports and they are located distal to the expandable member.
  • the side port adapted for passing fluids can also be adapted to allow for aspiration.
  • Another useful port has a valved gas inlet to allow for the entry and exit of various gases at a position distal to the expandable member so as to allow delivery of the gas directly into the body cavity.
  • passageways can be utilized to link the respective side ports with the expandable member and/or the distal end of the sleeve.
  • passages can be made within, or coupled to, the wall of the sleeve and the sleeve's outer tubular member.
  • the sleeve could be formed of various tubular members oriented concentrically within the sleeve's outer tubular member, providing separate or shared passages for each of the ports. With respect to the ports in communication with the distal end of the sleeve, it would also be possible to have these ports share a single passage formed by a single tubular member.
  • a typical use for the above described trocar assembly is described as follows.
  • the sharp end of the penetrating member is used to create an incision in the tissue surrounding the abdominal cavity.
  • a surgical incision may be made in the fascia and peritoneum within a purse string suture or other tightening technique, and a blunt tipped trocar may then be inserted through the hole which is then tightened around it.
  • the sleeve is then pushed to the desired depth within the cavity such that the expandable member on the sleeve is through the insertion site and in the cavity.
  • the expandable member is inflated or expanded so as to create a barrier between the cavity and insertion site by abutting against the inner or posterior aspect of the abdominal wall, thus engaging the abdominal wall.
  • the penetrating member is then removed from the sleeve and the external engaging means is positioned.
  • a clip can be slid distally along the tubular member until it is in engagement with the external or anterior aspect of the abdominal wall, at which point the clip is fixed into place.
  • the sleeve is now held firmly in place at the insertion site and the site is isolated from the peritoneal cavity.
  • the gas can be introduced in the side port having the gas valve inlet in order to pressurize the abdominal cavity.
  • An appropriate instrument can be inserted in the port at the proximal end of the sleeve. While manipulating the instrument in the abdominal cavity, a liquid capable of minimizing or eliminating cell adhesion can be introduced via a fluid line in the side port adapted for passing fluids in order to irrigate the cavity. The fluid can then be aspirated out of the cavity via a side port, and the irrigation and aspiration steps repeated as desired.
  • the side ports may be used simply for aspiration of accumulating serum, blood and/or any tumor cells which have gotten into the port.
  • the side ports can be used for the administration of other medicaments, such as local anesthetics, antibiotics, growth factors or cytotoxic agents, including osmotic agents, such as distilled and de-ionized water.
  • multiple trocar assemblies could be utilized. For example, if multiple trocar assemblies are required for the surgical procedure, then any or all of them can administer the liquid or medicament to each port site.
  • a central supply (container) of fluid branching out into different supply lines, such as flexible tubes may prove easier to use than separate fluid supplies.
  • the multiple lines can either branch directly out of the central container, or can branch out from a single line originating from the central container.
  • the branched out fluid lines would each attach to a side port of a different trocar assembly, and each line could have its own valve to independently control the flow of the liquid.
  • the multiple lines could be prevented from tangling with one another by securing each of them with a securing mechanism (such as a clip) to a stabilizing apparatus that would maintain the spacing of the lines at or near the point where they begin to diverge from one another.

Abstract

La présente invention concerne des substances et des procédés pour l'ajout de médicaments à un site récepteur ou d'accès. L'invention concerne également un procédé d'inhibition de fixation de cellules tumorales à un site récepteur ou d'accès.
PCT/US2000/027902 1999-10-08 2000-10-10 Procede d'administration de medicament a un site d'acces adapte au trocart WO2001026563A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US15823399P 1999-10-08 1999-10-08
US60/158,233 1999-10-08

Publications (1)

Publication Number Publication Date
WO2001026563A1 true WO2001026563A1 (fr) 2001-04-19

Family

ID=22567212

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2000/027902 WO2001026563A1 (fr) 1999-10-08 2000-10-10 Procede d'administration de medicament a un site d'acces adapte au trocart

Country Status (1)

Country Link
WO (1) WO2001026563A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US10028731B2 (en) 2013-11-12 2018-07-24 Genzyme Corporation Barrier application device

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5725553A (en) * 1996-02-29 1998-03-10 Moenning; Stephen P. Apparatus and method for protecting a port site opening in the wall of a body cavity
US5951588A (en) * 1996-02-29 1999-09-14 Moenning; Stephen P. Apparatus and method for protecting a port site opening in the wall of a body cavity

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5725553A (en) * 1996-02-29 1998-03-10 Moenning; Stephen P. Apparatus and method for protecting a port site opening in the wall of a body cavity
US5951588A (en) * 1996-02-29 1999-09-14 Moenning; Stephen P. Apparatus and method for protecting a port site opening in the wall of a body cavity

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
KAWAMURA ET AL.: "Gasless laparoscopically assisted colonic surgery", AM. J. SURG., vol. 177, no. 6, June 1999 (1999-06-01), pages 515 - 517, XP002938337 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US10028731B2 (en) 2013-11-12 2018-07-24 Genzyme Corporation Barrier application device

Similar Documents

Publication Publication Date Title
US6695815B2 (en) Minimally invasive medical apparatus for dispensing a biologically active compound and an associated medical procedure for dispensing a biologically active compound
US10813668B2 (en) Postpartum hemorrhage balloon system
US11253260B2 (en) Methods for diagnosing and delivering therapeutic interventions in the peritoneal cavity
US20080200933A1 (en) Surgical devices and methods for forming an anastomosis between organs by gaining access thereto through a natural orifice in the body
US20060079838A1 (en) Movable Balloon anchor for medical devices
US20080262406A1 (en) Securement device for shunt catheter and implantation method therefor
US20130138134A1 (en) Stent devices for support, controlled drug delivery and pain management after vaginal surgery
US11179178B2 (en) Vaginal positioner for uterine tamponade device and methods of using the same
WO2008101077A1 (fr) Dispositifs chirurgicaux utilisant une force magnétique pour former une anamostose
JP2002522149A (ja) 無縫合動脈切開シールを有する灌流カテーテルシステムおよびその使用方法
TW201029692A (en) Manifolds, systems, and methods for administering reduced pressure to a subcutaneous tissue site
JP2009101150A (ja) 外科手術処置における使用のための密封アンカー
AU6755500A (en) Clip-on access port and methods of use
CA2701609A1 (fr) Materiel de chirurgie endoscopique transluminale
AU2010213601B2 (en) Endoscopic forceps with removable handle
US20120130507A1 (en) Permanent umbilical hollow tube
Carus et al. Single-port laparoscopic reversal of Hartmann's procedure: technique and results
WO2001026563A1 (fr) Procede d'administration de medicament a un site d'acces adapte au trocart
WO2019121987A1 (fr) Canule
RU2223042C2 (ru) Способ позадилонной радикальной простактэктомии при раке предстательной железы
RU199824U1 (ru) Лапароскопический жидкостной регулируемый ретрактор
RU2708578C1 (ru) Хирургический диссектор, хирургическая система и способ диссекции тканей
RU30072U1 (ru) Устройство для гемостаза паренхиматозных органов
US20150150559A1 (en) Devices, systems, and methods for diagnosing and delivering therapeutic interventions in the peritoneal cavity
Ulker Keyless abdominal rope-lifting surgery (KARS)

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): JP US

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE

121 Ep: the epo has been informed by wipo that ep was designated in this application
DFPE Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101)
122 Ep: pct application non-entry in european phase
NENP Non-entry into the national phase

Ref country code: JP