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Feasibility of a multimodal 18F-FDG-directed lymph node surgical excisional biopsy approach for appropriate diagnostic tissue sampling in patients with suspected lymphoma
© Povoski et al.; licensee BioMed Central. 2015
Received: 19 January 2015
Accepted: 28 April 2015
Published: 8 May 2015
18F-FDG PET/CT imaging is widely utilized in the clinical evaluation of patients with suspected or documented lymphoma. The aim was to describe our cumulative experience with a multimodal 18F-FDG-directed lymph node surgical excisional biopsy approach in patients with suspected lymphoma.
Thirteen patients (mean age 51 (±16;22–76) years), with suspected new or suspected recurrent lymphoma suggested by 18F-FDG-avid lesions seen on prior diagnostic whole-body PET/CT imaging, were injected IV with 18F-FDG prior to undergoing same-day diagnostic lymph node surgical excisional biopsy in the operating room. Various 18F-FDG detection strategies were used on the day of surgery, including, (1) same-day pre-resection patient PET/CT; (2) intraoperative gamma probe assessment; (3) clinical scanner specimen PET/CT imaging of whole surgically excised tissue specimens; (4) specimen gamma well counts; and/or (5) same-day post-resection patient PET/CT.
Same-day 18F-FDG injection dose was 14.8 (±2.4;12.5-20.6) millicuries or 548 (±89;463–762) megabecquerels. Sites of 18F-FDG-avid lesions were 4 inguinal, 3 cervical, 3 abdominal/retroperitoneal, 2 axillary, and 1 gluteal region subcutaneous tissue. Same-day pre-resection patient PET/CT was performed on 6 patients. Intraoperative gamma probe assessment was performed on 13 patients. Clinical scanner PET/CT imaging of whole surgically excised tissue specimens was performed in 10 cases. Specimen gamma well counts were performed in 6 cases. Same-day post-resection patient PET/CT imaging was performed on 8 patients. Time from 18F-FDG injection to same-day pre-resection patient PET/CT, intraoperative gamma probe assessment, and same-day post-resection patient PET/CT were 76 (±8;64–84), 240 (±63;168–304), and 487 (±104;331–599) minutes, respectively. Time from 18F-FDG injection to clinical scanner PET/CT of whole surgically excised tissue specimens was 363 (±60;272–446) minutes. Time from 18F-FDG injection to specimen gamma well counts was 591 (±96;420–689) minutes. Intraoperative gamma probe assessment successfully identified 18F-FDG-avid lesions in 12/13 patients. Histopathologic evaluation confirmed lymphoma in 12/13 patients and benign disease in 1/13 patients.
A multimodal approach to 18F-FDG-directed lymph node surgical excisional biopsy for suspected lymphoma is technically feasible for guiding appropriate diagnostic tissue sampling of lymph nodes seen as 18F-FDG-avid lesions on diagnostic 18F-FDG PET/CT imaging.
Diagnostic 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) imaging is widely utilized in the clinical assessment of patients with lymphoma, including for initial staging, treatment monitoring during therapy, restaging after completion of therapy, and detection of suspected recurrent disease [1-13]. These various applications of diagnostic 18F-FDG PET/CT imaging can dramatically influence management/therapy recommendations for lymphoma patients and can have the potential to positively impact upon long-term patient outcomes.
The surgeon has continued to play an important role in facilitating the diagnostic pathway for patients with suspected new or suspected recurrent lymphoma, as the findings noted on diagnostic 18F-FDG PET/CT imaging that are considered suspicious for lymphoma frequently require the subsequent performance of a lymph node surgical excisional biopsy procedure for confirmation of a definitive diagnosis , as well as for histopathologic, immunophenotypic, flow cytometry, and molecular subtype analyses .
Over the last 15 years, there has been increasing interest by surgeons and nuclear medicine/molecular imaging physicians in utilizing 18F-FDG and PET/CT imaging technology to attempt to provide real-time information within the operative room and perioperative setting for cancer patients [16-75]. Specifically related to our collaborative efforts at The Ohio State University, we have previously investigated the use of a novel, multimodal imaging and detection approach involving perioperative patient and ex vivo surgical specimen 18F-FDG PET/CT imaging in combination with intraoperative 18F-FDG gamma probe detection . In this regard, the aim of this study was to describe our cumulative experience in patients with suspected new or suspected recurrent lymphoma with a multimodal approach to 18F-FDG-directed lymph node surgical excisional biopsy for guiding appropriate diagnostic tissue sampling of lymph nodes that are seen as 18F-FDG-avid lesions on prior diagnostic whole-body 18F-FDG PET/CT imaging.
All aspects of the current retrospective analysis were approved by the Cancer Institutional Review Board (IRB) at The Ohio State University Wexner Medical Center. The data for the current retrospective analysis were acquired from a master prospectively-maintained database (with database inclusion dates from June 2005 to June 2012), which were generated from the combination of several Cancer IRB-approved protocols, and which involved a multimodal imaging and detection approach to 18F-FDG-directed surgery for the localization and resection of 18F-FDG-avid lesions in patients with known and suspected malignancies. This multimodal imaging and detection approach to 18F-FDG-directed surgery included 166 patients who gave consent to participate in one of the IRB-approved protocols, and a total of 157 patients who eventually were taken to the operating room for 18F-FDG-directed surgery.
The imaging parameters of this multimodal imaging and detection approach to 18F-FDG-directed surgery have been previously described in significant detail elsewhere [61,74]. All participating patients received a same-day single-dose preoperative intravenous injection of 18F-FDG. All patients fasted for a minimum of 6 hours prior to receiving their same-day single-dose preoperative intravenous injection of 18F-FDG. Various 18F-FDG detection strategies were used, including: (1) same-day pre-resection whole body or limited field of view patient PET/CT scan (consisting of 6 to 8 field of view PET bed positions for whole body imaging with 2 minutes of PET imaging per each PET bed position or consisting of 1 to 3 field of view PET bed positions for limited field of view imaging with 2 minutes of PET imaging per each PET bed position); (2) intraoperative gamma probe assessment; (3) clinical scanner PET/CT imaging of whole surgically excised tissue specimens (consisting of 1 field of view PET bed position for 10 minutes); (4) specimen gamma well counting; and/or (5) same-day post-resection limited field of view patient PET/CT scan (consisting of 1 to 3 field of view PET bed positions, with 10 minutes of PET imaging per each PET bed position). The 18F-FDG PET/CT images were acquired on one of three clinical diagnostic scanners: (1) Siemens Biograph 16 (Siemens, Knoxville, Tennessee); (2) Phillips Gemini TF (Philips, Amsterdam, Netherlands); and (3) Siemens Biograph 64 Slice mCT (Siemens, Knoxville, Tennessee). The 18F-FDG PET/CT images were all analyzed on a Philips Extended Brilliance Work Station (Philips, Amsterdam, Netherlands). For each individual patient, the same-day preoperative diagnostic 18F-FDG PET/CT scan, the same-day postoperative diagnostic 18F-FDG PET/CT scan, and the whole surgically excised tissue specimen PET/CT scan were performed on the same clinical diagnostic scanner.
All presumed 18F-FDG-avid lesions seen on diagnostic 18F-FDG PET/CT imaging were reported out with a maximum standard uptake value (SUVmax) on each presumed 18F-FDG-avid lesion. Likewise, there was no “minimal set threshold value” for the SUVmax on any given presumed 18F-FDG-avid lesion to be considered as a designation of an “abnormal” hypermetabolic 18F-FDG-avid focus and to be reported out as “suspicious for malignancy”. Rather, the determination of any given presumed 18F-FDG-avid lesion to be considered as a designation of an “abnormal” hypermetabolic 18F-FDG-avid focus and to be reported out as “suspicious for malignancy” was considered more complex than simply being based upon its SUVmax, and also required the clinical judgment and expertise/experience of the reporting nuclear medicine physician.
Intraoperative gamma probe assessment was undertaken to all 18F-FDG-avid tissue sites using various combinations of 6 different available gamma detection probe systems that were synchronously or dissynchronously available during the study period. Intraoperative gamma probe assessment of 18F-FDG-avid tissue positivity was determined as based utilization of the concept of the three-sigma statistical threshold criteria. The three-sigma statistical threshold criteria for gamma probe positivity was previously popularized for radioimmunoguided surgery by Thurston [70,75-77], and the derivation of its application to 18F-FDG-avid tissue positivity was most recently articulated by Chapman et al. . The three-sigma statistical threshold criteria was calculated by taking the standard deviation derived from the normal background tissue count rate and multiplying that standard deviation by a factor of three, and then adding that number to the normal background tissue count rate [70,75-77]. Using this statistical threshold methodology, intraoperative gamma probe assessment of 18F-FDG-avid tissue positivity was confirmed when the count rate for the target tissue exceeded the three-sigma statistical threshold criteria [70,75]. A fixed ratiometric 18F-FDG-avid lesion-to-background count ratio threshold was not utilized for the determination of probe positivity.
All continuous variables were expressed as mean value (± standard deviation; range). The software program IBM SPSS® 21 for Windows® (SPSS, Inc., Chicago, Illinois) was used for the data analysis. All mean value comparisons for continuous variables were performed by using the 2-tailed paired samples t-test. All categorical variable comparisons were made using 2 x 2 contingency tables that were analyzed by either the Pearson chi-square test or the Fisher exact test, when appropriate. P-values determined to be 0.05 or less were considered to be statistically significant.
There were 13 patients with either suspected new lymphoma (n = 2) or suspected recurrent lymphoma (n = 11) that were available for the current analysis, as suggested by 18F-FDG-avid lesions seen on their prior diagnostic whole-body PET/CT imaging. This included 10 females and 3 males. Their mean age was 51 (±16; range, 22–76) years. The mean SUVmax for the hottest 18F-FDG-avid lesion seen on their most recent prior diagnostic whole-body PET/CT scans was 11.5 (±8.0; range, 1.7-25.6). The time of the most recent prior diagnostic whole-body PET/CT scan to the time of surgery was 13 (±17; range, 0–48) days.
The anatomical sites of the 18F-FDG-avid lesions were 4 inguinal/groin region sites, 3 cervical region sites, 3 abdominal/retroperitoneal sites, 2 axillary region sites, and 1 gluteal subcutaneous tissue site. These anatomical sites of the 18F-FDG-avid lesions were clinically palpable on physical examination in only 5 of the 13 patients.
Variables related to multimodal imaging and detection approach to 18 F-FDG-directed surgery
Mean value (± SD; range)
Same-day 18F-FDG injection dose
14.8 (±2.4; 12.5-20.6) millicuries; or
548 (±89; 463–762) megabecquerels
Time from 18F-FDG injection to same-day pre-resection patient PET/CT
76 (±8; 64–84) minutes
Time from 18F-FDG injection to intraoperative gamma probe assessment
240 (±63; 168–304) minutes
Time from 18F-FDG injection to same-day post-resection limited field of view patient PET/CT
487 (±104; 331–599) minutes
Time from 18F-FDG injection to clinical scanner specimen PET/CT of whole surgically excised tissue specimens
363 (±60; 272–446) minutes
Time from 18F-FDG injection to specimen gamma well counting
591 (±96; 420–689) minutes
A same-day pre-resection patient PET/CT imaging was performed on 6 patients, including 4 same-day pre-resection whole body patient PET/CT scans and 2 same-day pre-resection limited field of view patient PET/CT scans. Intraoperative gamma probe assessment was performed on all 13 patients. Clinical scanner specimen PET/CT imaging of whole surgically excised tissue specimens was performed in 10 cases. Specimen gamma well counting was performed in 6 cases. A same-day post-resection limited field of view patient PET/CT imaging was performed on 8 patients.
As shown in Table 1, the time from 18F-FDG injection to same-day pre-resection patient PET/CT was 76 (±8; range, 64–84) minutes. The time from 18F-FDG injection to intraoperative gamma probe assessment was 240 (±63; range, 168–304) minutes. The time from 18F-FDG injection to same-day post-resection limited field of view patient PET/CT was 487 (±104; range, 331–599) minutes. The time from 18F-FDG injection to clinical scanner specimen PET/CT of whole surgically excised tissue specimens was 363 (±60; range, 272–446) minutes. The time from 18F-FDG injection to specimen gamma well counting was 591 (±96; range, 420–689) minutes.
Intraoperative gamma probe assessment successfully identified the 18F-FDG-avid lesion as probe positive (i.e., the 18F-FDG-avid lesion/target tissue count rate exceeded the three-sigma statistical threshold criteria) in 12/13 patients that were probed. Clinical scanner specimen PET/CT imaging of whole surgically excised tissue specimens verified 18F-FDG avidity within the sampled tissue from all 10 cases that were scanned. Same-day post-resection limited field of view patient PET/CT imaging verified successful removal of the intended 18F-FDG-avid lesions in all 8 patients that were scanned.
Histopathologic evaluation confirmed lymphoma in 12/13 patients and benign disease (i.e., florid follicular hyperplasia) in 1/13 patients.
For lymphoma patients, it is well recognized that 18F-FDG PET/CT imaging, in contrast to conventional anatomic imaging modalities (i.e., computed tomography, ultrasonography, or magnetic resonance imaging), allows for improved initial staging, treatment monitoring during therapy, restaging after completion of therapy, and detection of recurrent disease in the absence of any notably clinical and/or biochemical disease manifestations [1-13]. Along similar lines, 18F-FDG PET/CT imaging allows for the recognition of a lesser degree of disease burden than is detectable on conventional anatomic imaging modalities, thus creating a situation in which patients with suspected new or suspected recurrent lymphoma will less frequently present with palpable adenopathy on clinical examination. Surgical biopsy continues to represent the principal diagnostic pathway by which a definitive tissue diagnosis is confirmed in patients with suspected new or suspected recurrent lymphoma . With the improved detection of more limited disease burden by 18F-FDG PET/CT imaging, which is more frequently associated with an inability to appreciate palpable adenopathy on clinical examination, the surgeon’s ability to successfully target the appropriate anatomical site of diagnostic tissue sampling for confirmation of the correct tissue diagnosis is made more challenging. Therefore, utilizing such innovative methodologies as a multimodal 18F-FDG-directed lymph node surgical excisional biopsy approach for guiding appropriate diagnostic tissue sampling of lymph nodes detected as 18F-FDG-avid lesions on diagnostic whole-body 18F-FDG PET/CT imaging can help the surgeon to maximize the likelihood of success in establishing the correct tissue diagnosis. Likewise, such methodologies have the potential for decreasing the degree of invasiveness as well as the degree of tissue disruption and tissue removal necessary for accomplishing successful tissue targeting.
Although we fully recognize that the current retrospective data analysis is based upon only 13 patients, the cases presented herein demonstrate that a multimodal 18F-FDG-directed lymph node surgical excisional biopsy approach for suspected lymphoma is technically feasible for guiding appropriate diagnostic tissue sampling of lymph nodes seen as 18F-FDG-avid lesions on diagnostic 18F-FDG PET/CT imaging, especially when such 18F-FDG-avid lesions are not easily appreciable as palpable adenopathy on clinical examination. Likewise, the conceptualization of this approach is well illustrated by the case presented in Figures 1 and 2. It is our belief that such a strategy can be best maximized when a multimodal imaging and detection approach is utilized involving perioperative patient and ex vivo surgical specimen 18F-FDG PET/CT imaging in combination with intraoperative 18F-FDG gamma probe detection. This line of reasoning has been validated by our group for a variety of disease-type-specific solid malignancies [16-18,33,35,36,38-41,43,44,46,47,52,61,69].
Along similar lines, three other groups of investigators have also previously described the successful utilization of commercially-available intraoperative hand-held gamma probe systems for 18F-FDG-directed lymph node surgical excisional biopsy in patients with suspected or documented lymphoma [27,31,50,67]. Gulec et al. described this technique in four patients in one report from 2006  and in six patients in another report from 2007 . Molina et al. described this technique in three patients in their report from 2009 . Vos et al. described this technique in one patient in their report from 2012 . However, none of these three other groups of investigators utilized perioperative patient and ex vivo surgical specimen 18F-FDG PET/CT imaging at the time of intraoperative 18F-FDG gamma probe detection, thus falling short of incorporating a multimodal approach to this sometimes challenging diagnostic dilemma.
The ability to successfully perform an 18F-FDG-directed lymph node surgical excisional biopsy procedure for suspected lymphoma is highly dependent upon the commercially-available intraoperative hand-held gamma probe that is used during such a surgical case. The most important performance parameters related to any given gamma detection probe system are generally thought to be: (1) overall sensitivity (i.e., efficiency); (2) spatial selectivity (i.e., radial sensitivity distribution); (3) spatial resolution (i.e., lateral sensitivity distribution); (4) energy resolution (i.e., spectral discrimination); and (5) contrast . The most widely utilized commercially-available intraoperative hand-held gamma probes are generally designed for detecting radioisotopes of gamma-ray energies in the low-energy emission (0 keV to 150 keV) range and medium-energy emission (150 keV to 400 keV) range, thus allowing successful detection of radioisotopes such as: (1) technetium-99 m (99mTc; 140 and 142 KeV; most commonly used for sentinel lymph node biopsy procedures and parathyroid surgery); (2) indium-111 (111In; 171 and 247 KeV; used with octreotide to detect neuroendocrine tumors); (3) iodine-123 (123I; 159 KeV; used with metaiodobenzylguanidine to detect neuroblastomas and pheochromocytomas); and (4) iodine-125 (125I; 35 KeV; previously used with anti-TAG-72 monoclonal antibodies and anti-CEA monoclonal antibodies during radioimmunoguided surgery) [46,70].
However, most commercially-available intraoperative hand-held gamma probes are not specifically designed to directly or indirectly detect the resultant 511 KeV gamma emissions following positron annihilation emanating from higher energy gamma photon emitting/positron emitting radionuclides such as fluorine-18 (18F) or iodine-124 (124I) [46,70]. Resultantly, there has been a recent appearance of commercially-available intraoperative hand-held gamma probes that are specifically intended for attempting to detect 511 KeV gamma emissions from higher energy gamma photon emitting/positron emitting radionuclides. These commercially-available intraoperative hand-held gamma probes have generally been designated as “PET” probes. The overall weight and physical size of any typical “PET” probe is generally a function of the degree of physical side shielding/collimation necessary to theoretically block adjacent background radiation, to limit the field of view, and to collimate the head of the probe, with the intention of limiting the area of tissue contributing to the probe count rate and of providing better spatial resolution between areas of tissue of differing radioactivity levels [46,70,78]. Attempts at improving the current “PET” probe design by further increasing physical side shielding/collimation or by increasing crystal diameter/thickness to capture a higher percentage of 511 KeV gamma emissions would only result in a “PET” probe configuration prohibitively large in physical size, heavy in weight, and which would be much more costly [46,70,78], thus representing significant obstacles to applying the currently commercially-available “PET” probes to the detection of 18F-FDG-avid tissues.
In order to attempt to bypass these physical barriers related to the degree of physical side shielding/collimation or crystal diameter/thickness in designing intraoperative hand-held gamma probes that are specifically intended for attempting to detect 511 KeV gamma emissions from higher energy gamma photon emitting/positron emitting radionuclides, engineering efforts have moved toward other directions for the adaptation of more novel “PET” probe designs that do not rely upon increasing physical side shielding/collimation or increasing crystal diameter/thickness. Examples of such alternative design concepts that can be adapted to “PET” probe design are secondary K-alpha x-ray fluorescence [70,78], active electronic collimation [28,54,58,60,67,79-81], and other crystal geometry designs using multiple small crystals with specific novel geometric configurations [82,83] for optimizing background rejection capabilities. These innovative alternative design schemas for detecting higher energy gamma photon emitting/positron emitting radionuclides, some of which have already been successfully applied to intraoperative hand-held gamma probe designs, are also the focus of current pre-clinical research that is actively looking at developing small platform, portable perioperative and intraoperative patient and ex vivo surgical specimen imaging devices with similar capabilities for detecting higher energy gamma photon emitting/positron emitting radionuclides. However, such small platform, portable perioperative and intraoperative patient and ex vivo surgical specimen imaging devices have not yet been fully realized or made commercially available for use in the clinical arena.
A multimodal approach to 18F-FDG-directed lymph node surgical excisional biopsy for suspected lymphoma is technically feasible for guiding appropriate diagnostic tissue sampling of lymph nodes seen as 18F-FDG-avid lesions on prior diagnostic whole-body 18F-FDG PET/CT imaging. This multimodal approach can be very helpful to the surgeon for accomplishing successful targeting of the appropriate anatomical sites (corresponding to 18F-FDG-avid lesions) for successful diagnostic tissue sampling in confirming the correct tissue diagnosis in challenging cases involving patients with non-palpable suspected new or suspected recurrent lymphoma.
The authors would like to thank the following people from The Ohio State University Wexner Medical Center for their ongoing assistance with the 18F-FDG-directed surgery program: Dr. Charles Hitchcock from the Department of Pathology; Dr. Michael V. Knopp from the Department of Radiology; Deborah Hurley, Marlene Wagonrod, and the entire staff of the Division of Molecular Imaging and Nuclear Medicine, Department of Radiology; Nichole Storey from the Department of Radiology; and the entire operating room staff from the Arthur G. James Cancer Hospital and Richard J. Solove Research Institute.
The content of this paper was presented as a poster presentation at the 67th Annual Society of Surgical Oncology Cancer Symposium in Phoenix, Arizona from March 12, 2014 to March 15, 2014.
- Baba S, Abe K, Isoda T, Maruoka Y, Sasaki M, Honda H. Impact of FDG-PET/CT in the management of lymphoma. Ann Nucl Med. 2011;25:701–16.View ArticlePubMedGoogle Scholar
- Zanoni L, Cerci JJ, Fanti S. Use of PET/CT to evaluate response to therapy in lymphoma. Q J Nucl Med Mol Imaging. 2011;55:633–47.PubMedGoogle Scholar
- Buchpiguel CA. Current status of PET/CT in the diagnosis and follow up of lymphomas. Rev Bras Hematol Hemoter. 2011;33:140–7.View ArticlePubMedPubMed CentralGoogle Scholar
- Ansell SM, Armitage JO. Positron emission tomographic scans in lymphoma: convention and controversy. Mayo Clin Proc. 2012;87:571–80.View ArticlePubMedPubMed CentralGoogle Scholar
- Alvarez Páez AM, Nogueiras Alonso JM, Serena Puig A. 18F-FDG-PET/CT in lymphoma: two decades of experience. Rev Esp Med Nucl Imagen Mol. 2012;31:340–9.PubMedGoogle Scholar
- Wu LM, Chen FY, Jiang XX, Gu HY, Yin Y, Xu JR. 18F-FDG PET, combined FDG-PET/CT and MRI for evaluation of bone marrow infiltration in staging of lymphoma: a systematic review and meta-analysis. Eur J Radiol. 2012;81:303–11.View ArticlePubMedGoogle Scholar
- Manohar K, Mittal BR, Bhattacharya A, Malhotra P, Varma S. Fluoro-deoxy-glucose positron emission tomography/computed tomography in lymphoma: a pictorial essay. Indian J Nucl Med. 2013;28:85–92.View ArticlePubMedPubMed CentralGoogle Scholar
- Kostakoglu L, Cheson BD. State-of-the-Art research on “lymphomas: role of molecular imaging for staging, prognostic evaluation, and treatment response”. Front Oncol. 2013;3:212.View ArticlePubMedPubMed CentralGoogle Scholar
- Allen-Auerbach M, de Vos S, Czernin J. PET/computed tomography and lymphoma. Radiol Clin North Am. 2013;51:833–44.View ArticlePubMedGoogle Scholar
- Kluge R, Kurch L, Montravers F, Mauz-Körholz C. FDG PET/CT in children and adolescents with lymphoma. Pediatr Radiol. 2013;43:406–17.View ArticlePubMedGoogle Scholar
- Nakayama M, Okizaki A, Ishitoya S, Sakaguchi M, Sato J, Aburano T. Dual-time-point F-18 FDG PET/CT imaging for differentiating the lymph nodes between malignant lymphoma and benign lesions. Ann Nucl Med. 2013;27:163–9.View ArticlePubMedGoogle Scholar
- Araf S, Montoto S. The use of interim (18)F-fluorodeoxyglucose PET to guide therapy in lymphoma. Future Oncol. 2013;9:807–15.View ArticlePubMedGoogle Scholar
- Barrington SF, Mikhaeel NG. When should FDG-PET be used in the modern management of lymphoma? Br J Haematol. 2014;164:315–28.View ArticlePubMedGoogle Scholar
- Morris-Stiff G, Cheang P, Key S, Verghese A, Havard TJ. Does the surgeon still have a role to play in the diagnosis and management of lymphomas? World J Surg Oncol. 2008;6:13.View ArticlePubMedPubMed CentralGoogle Scholar
- Jaffe ES, Banks PM, Nathwani B, Said J, Swerdlow SH, Ad Hoc Committee on reporting of lymphoid neoplasms; Association of Directors of Anatomic and Surgical Pathology. Recommendations for the reporting of lymphoid neoplasms: a report from the Association of Directors of Anatomic and Surgical Pathology. Mod Pathol. 2004;17:131–5.View ArticlePubMedGoogle Scholar
- Desai D, Arnold M, Saha S, Hinkle G, Soble D, Frye J, et al. Intraoperative gamma detection of FDG distribution in colorectal cancer. Clin Positron Imaging. 1999;2:325.View ArticlePubMedGoogle Scholar
- Desai DC, Arnold M, Saha S, Hinkle G, Soble D, Fry J, et al. Correlative whole-body FDG-PET and intraoperative gamma detection of FDG distribution in colorectal cancer. Clin Positron Imaging. 2000;3:189–96.View ArticlePubMedGoogle Scholar
- Zervos EE, Desai DC, DePalatis LR, Soble D, Martin EW. 18F-labeled fluorodeoxyglucose positron emission tomography-guided surgery for recurrent colorectal cancer: a feasibility study. J Surg Res. 2001;97:9–13.View ArticlePubMedGoogle Scholar
- Essner R, Hsueh EC, Haigh PI, Glass EC, Huynh Y, Daghighian F. Application of an [(18)F]fluorodeoxyglucose-sensitive probe for the intraoperative detection of malignancy. J Surg Res. 2001;96:120–6.View ArticlePubMedGoogle Scholar
- Essner R, Daghighian F, Giuliano AE. Advances in FDG PET probes in surgical oncology. Cancer J. 2002;8:100–8.View ArticlePubMedGoogle Scholar
- Higashi T, Saga T, Ishimori T, Mamede M, Ishizu K, Fujita T, et al. What is the most appropriate scan timing for intraoperative detection of malignancy using 18F-FDG-sensitive gamma probe? Preliminary phantom and preoperative patient study. Ann Nucl Med. 2004;18:105–14.View ArticlePubMedGoogle Scholar
- Yap JT, Carney JP, Hall NC, Townsend DW. Image-guided cancer therapy using PET/CT. Cancer J. 2004;10:221–33.View ArticlePubMedGoogle Scholar
- Barranger E, Kerrou K, Petegnief Y, David-Montefiore E, Cortez A, Daraï E. Laparoscopic resection of occult metastasis using the combination of FDG-positron emission tomography/computed tomography image fusion with intraoperative probe guidance in a woman with recurrent ovarian cancer. Gynecol Oncol. 2005;96:241–4.View ArticlePubMedGoogle Scholar
- Carrera D, Fernandez A, Estrada J, Martin-Comin J, Gamez C. Detection of occult malignant melanoma by 18F-FDG PET-CT and gamma probe. Rev Esp Med Nucl. 2005;24:410–3 [Spanish].View ArticlePubMedGoogle Scholar
- Franc BL, Mari C, Johnson D, Leong SP. The role of a positron- and high-energy gamma photon probe in intraoperative localization of recurrent melanoma. Clin Nucl Med. 2005;30:787–91.View ArticlePubMedGoogle Scholar
- Kraeber-Bodéré F, Cariou B, Curtet C, Bridji B, Rousseau C, Dravet F, et al. Feasibility and benefit of fluorine 18-fluoro-2-deoxyglucose-guided surgery in the management of radioiodine-negative differentiated thyroid carcinoma metastases. Surgery. 2005;138:1176–82.View ArticlePubMedGoogle Scholar
- Gulec SA, Daghighian F, Essner R. PET-Probe. Evaluation of Technical Performance and Clinical Utility of a Handheld High-Energy Gamma Probe in Oncologic Surgery. Ann Surg Oncol. 2006; Jul 24; [Epub ahead of print].Google Scholar
- Meller B, Sommer K, Gerl J, von Hof K, Surowiec A, Richter E, et al. High energy probe for detecting lymph node metastases with 18F-FDG in patients with head and neck cancer. Nuklearmedizin. 2006;45:153–9.PubMedGoogle Scholar
- Nwogu C, Fischer G, Tan D, Glinianski M, Lamonica D, Demmy T. Radioguided detection of lymph node metastasis in non-small cell lung cancer. Ann Thorac Surg. 2006;82:1815–20. discussion 1820.View ArticlePubMedGoogle Scholar
- Curtet C, Carlier T, Mirallié E, Bodet-Milin C, Rousseau C, Barbet J, et al. Prospective comparison of two gamma probes for intraoperative detection of 18F-FDG: in vitro assessment and clinical evaluation in differentiated thyroid cancer patients with iodine-negative recurrence. Eur J Nucl Med Mol Imaging. 2007;34:1556–62.View ArticlePubMedGoogle Scholar
- Gulec SA, Hoenie E, Hostetter R, Schwartzentruber D. PET probe-guided surgery: applications and clinical protocol. World J Surg Oncol. 2007;5:65.View ArticlePubMedPubMed CentralGoogle Scholar
- Gulec SA. PET probe-guided surgery. J Surg Oncol. 2007;96:353–7.View ArticlePubMedGoogle Scholar
- Hall NC, Povoski SP, Murrey DA, Knopp MV, Martin EW. Combined approach of perioperative 18F-FDG PET/CT imaging and intraoperative 18F-FDG handheld gamma probe detection for tumor localization and verification of complete tumor resection in breast cancer. World J Surg Oncol. 2007;5:143.View ArticlePubMedPubMed CentralGoogle Scholar
- Piert M, Burian M, Meisetschlager G, Stein HJ, Ziegler S, Nahrig J, et al. Positron detection for the intraoperative localisation of cancer deposits. Eur J Nucl Med Mol Imaging. 2007;34:1534–44.View ArticlePubMedPubMed CentralGoogle Scholar
- Sarikaya I, Povoski SP, Al-Saif OH, Kocak E, Bloomston M, Marsh S, et al. Combined use of preoperative 18F FDG-PET imaging and intraoperative gamma probe detection for accurate assessment of tumor recurrence in patients with colorectal cancer. World J Surg Oncol. 2007;5:80.View ArticlePubMedPubMed CentralGoogle Scholar
- Sun D, Bloomston M, Hinkle G, Al-Saif OH, Hall NC, Povoski SP, et al. Radioimmunoguided surgery (RIGS), PET/CT image-guided surgery, and fluorescence image-guided surgery: past, present, and future. J Surg Oncol. 2007;96:297–308.View ArticlePubMedGoogle Scholar
- Prior JO, Kosinski M, Delaloye AB, Denys A. Initial report of PET/CT-guided radiofrequency ablation of liver metastases. J Vasc Interv Radiol. 2007;18:801–3.View ArticlePubMedGoogle Scholar
- Agrawal A, Hall NC, Ringel MD, Povoski SP, Martin Jr EW. Combined use of perioperative TSH-stimulated 18F-FDG PET/CT imaging and gamma probe radioguided surgery to localize and verify resection of iodine scan-negative recurrent thyroid carcinoma. Laryngoscope. 2008;118:2190–4.View ArticlePubMedGoogle Scholar
- Cohn DE, Hall NC, Povoski SP, Seamon LG, Farrar WB, Martin Jr EW. Novel perioperative imaging with 18F-FDG PET/CT and intraoperative 18F-FDG detection using a handheld gamma probe in recurrent ovarian cancer. Gynecol Oncol. 2008;110:152–7.View ArticlePubMedGoogle Scholar
- Hall NC, Povoski SP, Murrey DA, Knopp MV, Martin EW. Bringing advanced medical imaging into the operative arena could revolutionize the surgical care of cancer patients. Expert Rev Med Devices. 2008;5:663–7.View ArticlePubMedGoogle Scholar
- Moffatt-Bruce SD, Povoski SP, Sharif S, Hall NC, Ross Jr P, Johnson MA, et al. A novel approach to positron emission tomography in lung cancer. Ann Thorac Surg. 2008;86:1355–7.View ArticlePubMedGoogle Scholar
- Piert M, Carey J, Clinthorne N. Probe-guided localization of cancer deposits using [(18)F]fluorodeoxyglucose. Q J Nucl Med Mol Imaging. 2008;52:37–49.PubMedGoogle Scholar
- Povoski SP, Hall NC, Martin EW, Walker MJ. Multimodality approach of perioperative 18F-FDG PET/CT imaging, intraoperative 18F-FDG handheld gamma probe detection, and intraoperative ultrasound for tumor localization and verification of resection of all sites of hypermetabolic activity in a case of occult recurrent metastatic melanoma. World J Surg Oncol. 2008;6:1.View ArticlePubMedPubMed CentralGoogle Scholar
- Povoski SP, Sarikaya I, White WC, Marsh SG, Hall NC, Hinkle GH, et al. Comprehensive evaluation of occupational radiation exposure to intraoperative and perioperative personnel from 18F-FDG radioguided surgical procedures. Eur J Nucl Med Mol Imaging. 2008;35:2026–34.View ArticlePubMedGoogle Scholar
- van Baardwijk A, Bosmans G, van Suylen RJ, van Kroonenburgh M, Hochstenbag M, Geskes G, et al. Correlation of intra-tumour heterogeneity on 18F-FDG PET with pathologic features in non-small cell lung cancer: a feasibility study. Radiother Oncol. 2008;87:55–8.View ArticlePubMedGoogle Scholar
- Povoski SP, Neff RL, Mojzisik CM, O’Malley DM, Hinkle GH, Hall NC, et al. A comprehensive overview of radioguided surgery using gamma detection probe technology. World J Surg Oncol. 2009;7:11.View ArticlePubMedPubMed CentralGoogle Scholar
- Murrey Jr DA, Bahnson EE, Hall NC, Povoski SP, Mojzisik CM, Young DC, et al. Perioperative (18)F-fluorodeoxyglucose-guided imaging using the becquerel as a quantitative measure for optimizing surgical resection in patients with advanced malignancy. Am J Surg. 2009;198:834–40.View ArticlePubMedGoogle Scholar
- Gollub MJ, Akhurst TJ, Williamson MJ, Shia J, Humm JL, Wong WD, et al. Feasibility of ex vivo FDG PET of the colon. Radiology. 2009;252:232–9.View ArticlePubMedGoogle Scholar
- Klaeser B, Mueller MD, Schmid RA, Guevara C, Krause T, Wiskirchen J. PET-CT-guided interventions in the management of FDG-positive lesions in patients suffering from solid malignancies: initial experiences. Eur Radiol. 2009;19:1780–5.View ArticlePubMedGoogle Scholar
- Molina MA, Goodwin WJ, Moffat FL, Serafini AN, Sfakianakis GN, Avisar E. Intra-operative use of PET probe for localization of FDG avid lesions. Cancer Imaging. 2009;9:59–62.View ArticlePubMedPubMed CentralGoogle Scholar
- Mallarajapatna GJ, Kallur KG, Ramanna NK, Susheela SP, Ramachandra PG. PET/CT-guided percutaneous biopsy of isolated intramuscular metastases from postcricoid cancer. J Nucl Med Technol. 2009;37:220–2.View ArticlePubMedGoogle Scholar
- Hall NC, Povoski SP, Murrey DA, Martin Jr EW, Knopp MV. Ex vivo specimen FDG PET/CT imaging for oncology. Radiology. 2010;255:663–4.View ArticlePubMedGoogle Scholar
- Nalley C, Wiebeck K, Bartel TB, Bodenner D, Stack Jr BC. Intraoperative radiation exposure with the use of (18)F-FDG-guided thyroid cancer surgery. Otolaryngol Head Neck Surg. 2010;142:281–3.View ArticlePubMedGoogle Scholar
- de Jong JS, van Ginkel RJ, Slart RH, Lemstra CL, Paans AM, Mulder NH, et al. FDG-PET probe-guided surgery for recurrent retroperitoneal testicular tumor recurrences. Eur J Surg Oncol. 2010;36:1092–5.View ArticlePubMedGoogle Scholar
- Hartemink KJ, Muller S, Smulders YM, Petrousjka van den Tol M, Comans EF. Fluorodeoxyglucose F18(FDG)-probe guided biopsy. Ned Tijdschr Geneeskd. 2010;154:A1884 [Dutch].PubMedGoogle Scholar
- Lee GO, Costouro NG, Groome T, Kashani-Sabet M, Leong SPL. The use of intraoperative PET probe to resect metastatic melanoma. BMJ Case Rep. 2010; doi:10.1136/bcr.12.2009.2593.Google Scholar
- Klaeser B, Wiskirchen J, Wartenberg J, Weitzel T, Schmid RA, Mueller MD, et al. PET/CT-guided biopsies of metabolically active bone lesions: applications and clinical impact. Eur J Nucl Med Mol Imaging. 2010;37:2027–36.View ArticlePubMedGoogle Scholar
- García JR, Fraile M, Soler M, Bechini J, Ayuso JR, Lomeña F. PET/CT-guided salvage surgery protocol. Results with ROLL Technique and PET probe. Rev Esp Med Nucl. 2011;30:217–22 [Spanish].View ArticlePubMedGoogle Scholar
- Kim WW, Kim JS, Hur SM, Kim SH, Lee SK, Choi JH, et al. Radioguided surgery using an intraoperative PET probe for tumor localization and verification of complete resection in differentiated thyroid cancer: a pilot study. Surgery. 2011;149:416–24.View ArticlePubMedGoogle Scholar
- Manca G, Biggi E, Lorenzoni A, Boni G, Roncella M, Ghilli M, et al. Simultaneous detection of breast tumor resection margins and radioguided sentinel node biopsy using an intraoperative electronically collimated probe with variable energy window: a case report. Clin Nucl Med. 2011;36:e196–8.View ArticlePubMedGoogle Scholar
- Povoski SP, Hall NC, Murrey Jr DA, Chow AZ, Gaglani JR, Bahnson EE, et al. Multimodal imaging and detection approach to 18F-FDG-directed surgery for patients with known or suspected malignancies: a comprehensive description of the specific methodology utilized in a single-institution cumulative retrospective experience. World J Surg Oncol. 2011;9:152.View ArticlePubMedPubMed CentralGoogle Scholar
- Tatli S, Gerbaudo VH, Feeley CM, Shyn PB, Tuncali K, Silverman SG. PET/CT-guided percutaneous biopsy of abdominal masses: initial experience. J Vasc Interv Radiol. 2011;22:507–14.View ArticlePubMedGoogle Scholar
- Werner MK, Aschoff P, Reimold M, Pfannenberg C. FDG-PET/CT-guided biopsy of bone metastases sets a new course in patient management after extensive imaging and multiple futile biopsies. Br J Radiol. 2011;84:e65–7.View ArticlePubMedGoogle Scholar
- Sainani NI, Shyn PB, Tatli S, Morrison PR, Tuncali K, Silverman SG. PET/CT-guided radiofrequency and cryoablation: is tumor fluorine-18 fluorodeoxyglucose activity dissipated by thermal ablation? J Vasc Interv Radiol. 2011;22:354–60.View ArticlePubMedGoogle Scholar
- Francis CL, Nalley C, Fan C, Bodenner D, Stack Jr BC. 18F-fluorodeoxyglucose and 131I Radioguided Surgical Management of Thyroid Cancer. Otolaryngol Head Neck Surg. 2012;146:26–32.View ArticlePubMedGoogle Scholar
- Bains S, Reimert M, Win AZ, Khan S, Aparici CM. A patient with psoriatic arthritis imaged with FDG-PET/CT demonstrated an unusual imaging pattern with muscle and fascia involvement: a case report. Nucl Med Mol Imaging. 2012;46:138–43.View ArticlePubMedPubMed CentralGoogle Scholar
- Vos CG, Hartemink KJ, Muller S, Oosterhuis JW, Meijer S, van den Tol MP, et al. Clinical applications of FDG-probe guided surgery. Acta Chir Belg. 2012;112:414–8.View ArticlePubMedGoogle Scholar
- Hall N, Murrey D, Povoski S, Barker D, Zhang J, Bahnson E, et al. Evaluation of 18FDG PET/CT image quality with prolonged injection-to-scan times. Mol Imaging Biol. 2012;14(2, supplement):P610.Google Scholar
- Hall NC, Povoski SP, Zhang J, Knopp MV, Martin Jr EW. Use of intraoperative nuclear medicine imaging technology: strategy for improved patient management. Expert Rev Med Devices. 2013;10:149–52.View ArticlePubMedGoogle Scholar
- Povoski SP, Chapman GJ, Murrey Jr DA, Lee R, Martin Jr EW, Hall NC. Intraoperative detection of 18F-FDG-avid tissue sites using the increased probe counting efficiency of the K-alpha probe design and variance-based statistical analysis with the three-sigma criteria. BMC Cancer. 2013;13:98.View ArticlePubMedPubMed CentralGoogle Scholar
- Cerci JJ, Pereira Neto CC, Krauzer C, Sakamoto DG, Vitola JV. The impact of coaxial core biopsy guided by FDG PET/CT in oncological patients. Eur J Nucl Med Mol Imaging. 2013;40:98–103.View ArticlePubMedGoogle Scholar
- Win AZ, Aparici CM. Real-time FDG PET/CT-guided bone biopsy in a patient with two primary malignancies. Eur J Nucl Med Mol Imaging. 2013;40:1787–8.View ArticlePubMedGoogle Scholar
- Cerci JJ, Huber FZT, Bogoni M. PET/CT-guided biopsy of liver lesions. Clin Transl Imaging. 2014;2:157–63.View ArticleGoogle Scholar
- Povoski SP, Murrey Jr DA, Smith SM, Martin Jr EW, Hall NC. 18F-FDG PET/CT oncologic imaging at extended injection-to-scan acquisition time intervals derived from a single-institution 18F-FDG-directed surgery experience: feasibility and quantification of 18F-FDG accumulation within 18F-FDG-avid lesions and background tissues. BMC Cancer. 2014;14:453.View ArticlePubMedPubMed CentralGoogle Scholar
- Chapman GJ, Povoski SP, Hall NC, Murrey Jr DA, Lee R, Martin Jr EW. Comparison of two threshold detection criteria methodologies for determination of probe positivity for intraoperative in situ identification of presumed abnormal 18F-FDG-avid tissue sites during radioguided oncologic surgery. BMC Cancer. 2014;14:667.View ArticlePubMedPubMed CentralGoogle Scholar
- Thurston MO. Development of the gamma-detecting probe for radioimmunoguided surgery. In: Martin EW, editor. Radioimmunoguided Surgery (RIGS) in the Detection and Treatment of Colorectal Cancer, 1st edition. Austin: R.G. Landes Company; 1994. p. 41–65.Google Scholar
- Martin Jr EW, Thurston MO. The use of monoclonal antibodies (MAbs) and the development of an intraoperative hand-held probe for cancer detection. Cancer Invest. 1996;14:560–71.View ArticlePubMedGoogle Scholar
- Martin EW, Chapman GJ, Subramaniam VV, Povoski SP. Intraoperative detection of gamma emissions using K-alpha X-ray fluorescence. Expert Rev Med Devices. 2010;7:431–4.View ArticlePubMedGoogle Scholar
- GFE Gesellschaft für Forschungs und Entwicklungsservice mbH); Gamma Locator DXI: [http://www.gfe-service.de/en/ylocator.php].
- Gerl J, Ameil F, Kojouharov Z, , Surowiec D. High energy gamma probe with position sensing capability. European Patent EP 1 596 223 B1; Filed May 10, 2005; Published January 21, 2009.Google Scholar
- Gerl J. Kojouharov Z, Ameil E, Surowiec D. High energy gamma probe with position sensing capability. United States Patent US 7,312,460 B2; Filed May 10, 2005; Published December 25, 2007.Google Scholar
- Lecomte R, Schmitt D, Lamoureux G. Geometry study of a high resolution PET detection system using small detectors. IEEE T Nucl Sci. 1984;31:556–61.View ArticleGoogle Scholar
- Levin CS. New imaging technologies to enhance the molecular sensitivity of positron emission tomography. Proc IEEE. 2008;96:439–67.View ArticleGoogle Scholar
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