Surgery

June 2017, Dr. Emily Bergsland received the Ernest H. Rosenbaum, M.D., Commitment to Patient Care Award for her long-standing dedication to her patients and ongoing efforts to improve care for people with neuroendocrine tumors. The award recognizes clinicians who are deeply committed to the highest quality patient care.

 

In December 2016, Dr. Thomas Hope received the first NETRF/ERF Nuclear Medicine Pilot Research Grant. The Neuroendocrine Tumor Research Foundation (NETRF) established the grant to explore innovations in nuclear medicine focused on diagnosis and treatment. The Education and Research Foundation for Nuclear Medicine and Molecular Imaging (ERF) solicited proposals and convened the scientific review panel to select the recipient. Hope’s project is titled “Intra-Arterial Peptide Receptor Radionuclide Therapy (I-A PRRT) using 90Y DOTA-TOC.” The primary goals are to evaluate possible liver, bone marrow and kidney toxicity after hepatic arterial injection and to evaluate imaging tumor response three months after treatment. Dr. Hope’s principal co-investigators are Dr. Emily Bergsland and Dr. Nicholas Fidelman.

 

In 2016, the Neuroendocrine Tumor Research Foundation recognized Dr. Eric Nakakura for his projected titled “Development of a Mouse Model of Pancreatic Neuroendocrine Cancer.” His xenograft mouse model will be useful in helping develop and test potential new therapies for pancreatic neuroendocrine tumors.

 

In 2016, the Neuroendocrine Tumor Research Foundation named Dr. Michael Germanthe NETRF Petersen Investigator for his project titled, “Treating Neuroendocrine Tumors via Synthetic Lethality.” His research aims to analyze how certain pathways interact to control neuroendocrine cell survival and death, and to evaluate synthetic lethal interactions—a gene therapy targeting cancer cells—in a patient-derived xenograft tumor model of pancreatic neuroendocrine tumors.

 


At UCSF, we have extensive experience evaluating patients and performing complex operations for neuroendocrine tumors.  

The goals of surgery include the safe and efficient:

  1. Evaluation of the extent of disease;
  2. Removal of the primary tumor;
  3. Removal of neighboring lymph nodes/mesenteric fibrosis;
  4. Removal of disease in the liver (if feasible) and ovaries;
  5. Removal of gallbladder (for patients with advanced disease). 

 

  1. Evaluation of the extent of disease
    At the beginning of surgery, it is critically important to determine the extent of disease.  We carefully examine by sight and touch all the surfaces of the abdomen, including the lining of the body wall (peritoneum), diaphragms, liver, intestines, and ovaries.  We perform intraoperative ultrasound of the liver by placing the probe directly on the liver surface, providing superior detection of very small tumors, not possible by CT scan or MRI.
     
  2. Removal of the primary tumor(s)
    For small intestine neuroendocrine tumors (SI-NETs), we remove a segment of intestine containing the primary tumor(s).  We carefully palpate the entire intestine, feeling for small primary tumors.  In most patients, we detect more than one primary tumor by meticulous palpation.  By careful palpation, we are able to find small primary tumors, many of which have remained elusive.  In fact, many patients we see are told that they have an unknown primary tumor.  We are very successful in finding these so called unknown primary tumors by actively looking and feeling for them.  We feel these unknown primary tumors are really unrecognized primary tumors.  For SI-NETs, we can often use minimally invasive, or laparoscopic, surgery, which minimizes pain and hastens recovery.

    For pancreatic NETs (PNETs), surgery is tailored to the type and location of the primary tumor.  We are often able to remove the PNETs using minimally invasive, or laparoscopic, surgery.  When necessary, we also perform complex pancreatic surgeries, including the Whipple procedure and blood vessel resections, safely and efficiently.  For patients with rare genetic conditions, such as MEN1, we tailor our treatment based on a patient’s age, tumor type/size, and other factors.
     
  3. Removal of neighboring lymph nodes/mesenteric fibrosis
    For SI-NETs, the tumor often spreads to neighboring lymph nodes, causing a scarring reaction in the tissues (mesenteric fibrosis).  This scarring reaction buckles the intestine, resulting in intestinal blockage, which may manifest as abdominal pain, bloating, nausea, vomiting, weight loss, and diarrhea.  Therefore, it is critical to remove the neighboring lymph nodes/mesenteric fibrosis along with the primary tumor(s).  We take much care to not injure the blood supply to the intestine, so we can preserve as much length of normal intestine as possible to optimize digestive function.

    For small PNETs producing insulin (insulin), we typically only remove the primary tumor, which is often not cancerous.  Therefore, for small insulinomas, we usually do not need to remove any neighboring lymph nodes.  For all other PNETs, it is essential remove the neighboring lymph nodes to determine if the tumors are cancerous.
     
  4. Removal of disease in the liver (if feasible) and ovaries
    In carefully selected patients, removal of disease in the liver and ovaries may be done.  The goals of surgery are to remove most, if not all, of visible liver disease, if feasible.  If this can be done, patients do better.  For tumors that produce hormones, removal of liver disease may dramatically improve symptoms, such as diarrhea and flushing.  We can often remove extensive liver disease by preserving most of the normal liver using a technique called enucleation.  Enucleation of liver tumors is like using a melon scoop to remove the tumors from the liver—essentially all the tumor is removed but none of the normal liver.  Sometimes we use energy (microwave ablation) to destroy liver tumors that are not amenable to safe removal. 

    Spread of tumor to the ovaries can also cause significant diarrhea and flushing; therefore, ovarian tumors should be removed if present.
     
  5. Removal of gallbladder (for patients with advanced disease)
    For patients with advanced disease, we will consider removing the gallbladder.  Many of these patients will receive somatostatin analog therapy (octreotide or lanreotide), commonly resulting in gallstones.  If gallbladder removal is straightforward, we will remove it.  For patients with liver disease, removal of the gallbladder will permit future liver directed therapies, which might not be feasible if the tumor is situated close to the gallbladder.

 

What is PRRT?

PRRT (177Lu-DOTATATE) is currently available at UCSF.

For evaluation, please request an appointment.

PRRT stands for Peptide Receptor Radionuclide Therapy.  Peptide refers to a small molecule that is very similar to the naturally occurring hormone somatostatin.  We call it a somatostatin analog, meaning that it is similar but not identical to somatostatin.  There are a number of somatostatin analogs that are use in patients with neuroendocrine tumors including octreotide, sandostatin, lanreotide.  These peptides bind to the somatostatin receptor that is expressed on the majority of neuroendocrine tumor cells. 

 

When binding to these receptors the peptide is brought into the tumor cell and stays there.  Because neuroendocrine tumor cells are one of the few cells in the body that express somatostatin receptors, we are able to target our peptide to the tumor cells using the receptor.  Radionuclide refers to the radiation that we attach to the peptide. 

 

There are different types of radiation that we can use, but in PRRT all the radiation given off is the type that can be used to kill cells.  Therapy refers to the idea that we are using peptides to target the receptors and bring the radionuclide into the tumor cells in order to treat the cells.  That is PRRT.

 

 

Published guidelines for treatment of NETs

UCSF Drs. Eric Nakakura and Emily Bergsland discuss carcinoid syndrome on ITV

 June 20, 2016


 

Dr. Emily Bergsland - NET Primer

January 24, 2016


 

The Patient & Family Neuroendocrine Tumor (NET) 2016 Conference

January 2016, Mission Bay Conference Center

Hosted by the HDFCCC in cooperation with NorCal CarciNET, NET Research Foundation, and Stanford University Medical Center