Biospecimen Collection During Intraoperative Consultation

Intraoperative Consultation as A Site for Collection

In this chapter we evaluate opportunities for the collection of biospecimens during intraoperative consultation (IOC). Because the majority of consultations occur in the context of cancer surgeries, we will focus here on the collection of biospecimens from patients with cancer and on the benefits and opportunities of these specimens for cancer research. We argue that the intraoperative consultation (IOC) suite is an ideal location for the efficient collection of samples from biospecimens, both for immediate treatment decisions and for purposes of biobanking and future translational research ( Table 21-1 ). However, the procurement must be arranged in a way that it does not disrupt workflow and work dynamics. We describe the logistics, infrastructure, workflow, data collection, and regulatory issues that need to be in place for this purpose.

In addition to the general biobanking infrastructure, the IOC suite requires specific configuration and equipment for biobanking. The minimal equipment that is needed within the IOC suite is a small workstation for grossing and room for a tissue collection specialist. A computer station with a printer for bar codes must also be nearby. In addition, for rapid freezing and temporary storage of biospecimens, a freezing bath device such as HistoChill (SP Scientific, Warmister PA) and a – 80 ^o C freezer are required.

Advantages of Tissue Collection in the IOC Suite

Tissue procurement in the IOC suite has multiple advantages over the regular procurement in the pathology laboratory or grossing room ( Table 21-1 ). Because it is feasible to keep collection times for biospecimens short, the quality of samples can be improved. To ensure a high quality of routinely collected specimens, the biobank must have a courier system that is responsible for the rapid transport of specimens from the operating room (OR) to the grossing station. In contrast, a biobanking courier is not needed when specimens are collected in the IOC room because the hospital is responsible for the expedited delivery. Thus the transport from the OR to the IOC is free of charge to the biobank. When specimens arrive in the IOC room, a receptionist accessions them immediately. The receptionist can be instructed to inform the biobanking team of the arrival of the specimen. This avoids the often time-consuming interactions between the biobank and the OR for the timely pickup of specimens. These logistics of specimen transport and accessioning that are set in place for IOCs provide a tremendous benefit to the biobank.

The Role of the Pathologist

In the biobanking team effort, the pathologist assumes a novel and central role to facilitate the molecular analysis of tissues for basic, translational, and clinical research. Understanding the starting material, from which data is generated, is critical. Until recently, modern analytical technologies of next-generation sequencing and array platforms that reveal genomic alterations in cancers have only been available for research purposes. However, recently this instrumentation and methodology have moved into Clinical Laboratory Improvement Amendments (CLIA)-certified laboratories, and today genomic data are guiding the clinical management of patients (Lim et al, 2011). This puts pathologists into the driver's seat for recommendations on delivery of individualized treatments and for bringing the right drug to the right patient. In this new role, pathologists have to extend their interdisciplinary activities. They should understand the terminology from various research areas that interact to bring genomic data to clinical applications, including genomics experts in basic cancer biology laboratories, physicians conducting early phase clinical trials, bioethicists, and computational biostatisticians. Thus, by collecting, coordinating, and interpreting the molecular analysis of biospecimens, pathologists are empowered through the genomic revolution to play an important role in the era of individualized and precision medicine.

Challenges to the Clinical Workflow Through Tissue Collection in the IOC

A major challenge for tissue procurement during IOC is the integration of clinical care and sample collection ( Figure 21-1 ). The timely collection of tissue involves a close collaboration between the personnel who handles the specimen, the pathologist rendering the frozen section diagnosis, and the biobank team. The demand on personnel in the IOC is particularly severe when multiple cases arrive simultaneously. Under these circumstances, patient care takes priority over research, and the collection of samples for the biobank is delayed until after the diagnosis has been communicated to the surgeon. The delay may reduce the tissue quality, in particular because lengthy ischemia times change the expression of labile bioanalytes. When the blood supply to the cancer is severed during surgery, the tissue becomes anoxic. The time period during which the tissue remains at 37 ^o C in the patient is referred to as “warm ischemia” time, and it is well known that prolonged warm ischemia time alters gene expression (Ma et al, 2012). During transit of the biospecimen, the ischemia continues at room temperature and is referred to as “cold ischemia time.” Similar to warm ischemia, cold ischemia can also compromise tissue quality (Bao et al, 2013). While there is no control over the duration of warm ischemia, it is feasible to limit the cold ischemia time. In fact, the best practices recommendations that are issued by the National Institute of Health, limit the time period between removal of the specimen from the patient and freezing or fixation to 30 minutes. However, some studies demonstrate high tissue quality despite longer transit and cold ischemia times (Esgueva et al, 2012). If the cold ischemia time cannot be limited to 30 minutes, it is important that time points of specimen arrival in the IOC room and freezing/fixation are recorded and entered into the specimen database in a searchable format. Thereby, at the time of tissue request, those specimens that may not have been frozen quickly can be identified and excluded for research studies that involve labile bioanalytes.

While it is clear that patient care is prioritized over research, it is important that samples are frozen for the biobank in the most expedited fashion. When starting a biobanking service, it may take time until the tissue harvest is seamlessly integrated into the operations in the IOC room ( Figure 21-1 ). Once the pathologists incorporate the biobanking into the workflow of the specimen, the provision of tissue samples from specimens to the biobanking staff is smooth and without difficulties. The biobanking team respects the clinical activities during preparation and microscopic inspection of frozen sections and waits until time is ready for obtaining tissue samples. When working with the pathologist, members of the biobank will enforce the biobank standard operating procedures (SOPs) so that they receive the correct samples. Thus the biobank team must be well prepared for each case and approach the collection in a systematic and organized way. This includes labeling the collection vials ahead of time and assisting the pathologist in the accurate and rapid execution of the biobanking SOPs.

Under specific circumstances and with the subspecialization of pathologists, some biobanks have been able to implement ultrafast collection protocols. Under these protocols, tissue samples are frozen within 5 minutes of specimen receipt. In most cases, the pathologist is involved in the research project that utilizes the specimens. The rapid freezing protocol is critical when the bioanalytes of interest are labile. For example, metabolic biomarkers or phosphorylation sites in proteins can rapidly vanish and need quick stabilization through freezing or fixation.

Coordination of Tissue-Collection Locations

While in most cases, biobanking in the IOC does not require intensive coordination by the biobank staff with the OR personnel and surgeon, certain exceptions exist. Some surgeons will routinely ask ahead of time for IOCs, whereas others will make a decision in the middle of their surgery. Often only the margins are sent for intraoperative inspection, while the main specimen takes the regular route to the pathology laboratory. In such cases, the biobanking team tracks the surgeries and, through communications with the OR, makes sure that the specimen is not mistakenly placed in formalin ( Figure 21-1 ). At the beginning of a normal day, the biobank reviews the OR schedule and identifies patients who have consented to tissue donations prior to their surgery. These cases are entered into the database and prepared for the collection of biological specimens. Medical records are only reviewed with permission from patients, and data that pertain to demographics, preoperative studies, and medications are collected by the biobank. Occasionally, consent can only be obtained after the surgery. If the surgeon informs the biobank that he or she plans to obtain consent postoperatively, the biobank may collect specimens under the medical record number but complete the data entry only after the patient has provided consent. Thus it is important to have a system in place that allows the tracking of the consent status and flagging of cases that are awaiting consent. As a last resource and under the auspices of an institutional review board (IRB) protocol, collecting samples may be permitted under a waiver of consent if the specimens are anonymized shortly after collection.

All samples that are collected by the biobank must be coded at the earliest possible time during the collection to minimize the risk of breach in privacy. The best method for coding is to label cryovials and cryomolds with a bar code that contains the study ID number of the case prior to specimen collection. Thus bar codes are generated when the case is first entered into the biobank database, which usually happens before the surgery, when a member of the biobank picks up the patient’s preoperation blood samples and a copy of the consent from the OR. The bar code is linked to the medical records number in a secure location in agreement with Health Insurance Portability and Accountability Act (HIPAA) regulations. In addition to the study ID number, letters identifying the type of tissue and location of the sample in the specimen can be included into the bar code. These letters ease the identification of samples at the time of retrieval from the biobank storage facility. All the information that is used for labeling a specimen should be included in the bar code, and handwriting of tubes should be discouraged to reduce human error and increase efficiency.