Method to induce exfoliation of cells and/or tissue fragments for enhanced cytopathologic cell collection

Abstract

Methods and techniques for obtaining enriched cell samples from an organ in a subject using an ultrasound contrast agent and insonating. Contiguous fragments of epithelia are obtained which are useful for subsequent histological analysis and for informing therapy and other medical considerations.

What is claimed is: 
     
         1 . A method of obtaining a sample of contiguous pancreatic duct cells from a subject comprising:
 administering to the subject, within one hour before or after initiation of insonation with ultrasonic energy, an amount of a secretin polypeptide effective to elicit pancreatic secretion; insonating a pancreas of the subject with an amount of ultrasonic energy at a Mechanical Index of from 0.03 to 1.3 from a multi-frequency array effective to achieve an asymmetric ultrasound wave at a predetermined point in the pancreas and elicit exfoliation of cells into a duct of a pancreas in the subject; and then   removing a sample of fluid containing contiguous pancreatic duct cells from the subject.   
     
     
         2 . The method of  claim 1 , wherein the contiguous pancreatic duct cells comprise epithelial cells. 
     
     
         3 . The method of  claim 1 , wherein an epithelia tissue fragment of an epithelia of the organ is exfoliated. 
     
     
         4 . The method of  claim 1 , wherein the organ is a bladder, breast, liver, kidney, lung thyroid, gastrointestinal tract or pancreas. 
     
     
         5 . The method of  claim 4 , further comprising removing a sample of fluid containing the cells from the subject. 
     
     
         6 . The method of  claim 5 , wherein the sample of fluid is obtained from a cyst of the organ or from a secretion of the organ. 
     
     
         7 . A method of obtaining pancreatic cells from a subject comprising:
 administering an amount of an ultrasound contrast agent to the subject; and   insonating a pancreas of the subject to an amount of ultrasonic energy effective to elicit stable cavitation of an ultrasound contrast agent,   so as to thereby elicit exfoliation of cells into a duct of a pancreas in a subject.   
     
     
         8 . The method of  claim 7 , wherein the ultrasonic energy does not exceed a Mechanical Index of 0.03, or does not exceed a Mechanical Index of 0.05. 
     
     
         9 . The method of  claim 7  further comprising insonating a pancreas of the subject with an amount of ultrasonic energy from a multi-frequency array effective to achieve an asymmetric ultrasound wave at a predetermined point in the pancreas and elicit exfoliation of cells into a duct of a pancreas in the subject. 
     
     
         10 . The method of  claim 7 , further comprising positioning a catheter or other collecting device at an opening of a pancreatic duct in the subject. 
     
     
         11 . The method of  claim 10 , wherein the opening of a pancreatic duct is a duodenal papilla. 
     
     
         12 . The method of  claim 10 , further comprising obtaining a sample of pancreatic secretion using the catheter or other collecting device. 
     
     
         13 . The method of  claim 12 , further comprising analyzing the sample of the pancreatic secretion obtained so as to determine if the sample contains pancreatic cancer cells or pancreatic dysplasia cells, or is non-pathological. 
     
     
         14 . A method of treating a subject for a pancreatic disorder comprising:
 a) determining if the subject has pancreatic dysplastic cells or pancreatic cancer cells in their pancreas by the method of  claim 13 , and   b) effecting chemotherapy, radiotherapy, immunotherapy or a pancreatectomy in a subject found in a) to have pancreatic dysplastic cells or pancreatic cancer cells in their pancreas.   
     
     
         15 . The method of  claim 14 , wherein determining if the subject has pancreatic dysplastic cells or pancreatic cancer cells in their pancreas is effected through one or more of cellular morphological analysis, tissue morphological analysis, or biomolecular marker analysis.