Post Treatment Follow up of Prostate Cancer. Fluoride PET/CT Skull Base to Mid-Thigh Fluoride PET/CT is not routinely used in the evaluation of prostate cancer recurrence. There is limited evidence to support its use in this setting. FDG-PET/CT Some foci of metastatic prostate cancer demonstrate increased accumulation of fluorine-18-2-fluoro-2-deoxy-D- glucose (FDG) radiotracer, although this uptake is generally low compared to the other cancers. In 1 study, FDG- PET identified local or metastatic disease in only 28 of 91 patients (31%) with BCR after RP for prostate cancer [79]. FDG-PET is relatively insensitive in detecting osseous metastases compared to standard bone scintigraphy [80]. Ghanem et al [81] have demonstrated that FDG-PET alone or using PET/CT image fusion is less sensitive than MRI in the detection of bone metastases. In the routine setting, FDG-PET has little usefulness in the setting of BCR. However, as advanced metastatic prostate cancer migrates to a high Gleason grade, dedifferentiates, or transforms to other aggressive variants, such as small cell type, the tumor cells are more likely to convert to a higher glucose metabolism, and FDG can become useful in detection and monitoring of this subset of patients. Post-Treatment Follow-up of Prostate Cancer choline PET in staging and restaging of prostate cancer [84]. In intrapatient comparisons of PSMA and fluciclovine, a higher detection rate by PSMA for extraprostatic disease especially at lower PSA levels was reported, with superiority of fluciclovine for the prostate bed, because of significantly lower urinary excretion of fluciclovine compared with PSMA [85,86]. Ga-68 has a physical half-life of 68 minutes, and its production currently requires a generator, which can allow batch production of approximately 2 to 4 patient doses per generator elution [87]. In addition, PSMA PET radiotracers may be useful to select patients for PSMA radioligand therapy, which is recently FDA approved [88].


Post Treatment Follow up of Prostate Cancer. DCFPyL has a half-life of 110 minutes, and its production does not require an on-site cyclotron. Similar to PSMA PET tracer, DCFPyL may be useful to select patients for PSMA therapy, which is recently approved by FDA [88]. Radiography Skeletal Survey Radiographic survey is not routinely used in the evaluation of prostate cancer recurrence. Variant 2: Prostate cancer follow-up. Clinical concern for residual or recurrent disease after nonsurgical local and pelvic treatments. This variant covers the evaluation of BCR in the setting of a broad range of failed treatments targeted locally or to the pelvis, other than RP that is specifically covered in Variant 1. This includes primary radiation therapies, ablation therapies, and secondarily failed salvage therapies, such as failed salvage RT done after RP. RT is commonly performed in the setting of BCR after RP. Guidelines were published in 2013 jointly by ASTRO/AUA and largely endorsed by the American Society of Clinical Oncology [23]. There are 2 distinct clinical scenarios: adjuvant therapy and salvage therapy. It is known that patients with adverse risk factors found at the time of RP (high Gleason scores and/or adverse pathology, extracapsular extension or T4 invasion, seminal vesicle invasion, or positive margins) are at increased risk for BCR [99-105]. In this subgroup, there is consideration for adjuvant RT intended to reduce the high Post-Treatment Follow-up of Prostate Cancer likelihood of recurrence and progression of disease, which is commonly performed approximately 4 to 6 months after surgery. There is strong evidence that adjuvant RT in this setting reduces the risk of BCR and clinical progression of cancer, but the evidence is much less clear on the impact on overall survival. BCR is associated with subsequent progression to metastatic disease and death.


Post Treatment Follow up of Prostate Cancer. In patients who experience BCR after RP, radiation can be given in this setting as a salvage treatment and per ASTRO/AUA should be offered to patients who do not have evidence of metastatic disease. Regarding imaging after failure of adjuvant or salvage therapy, the literature is less rigorous. However, there are some concepts that warrant recognition. The radiation port is designed to spare toxicity to the rectum, and, after failed whole-pelvis RT, the mesorectal and presacral regions that saw much lower radiation dose are a particular area where recurrences are often identified and warrant scrutiny [9]. Additionally, the nodal and bone metastases that are identified in this setting are often in the high pelvis near the level of the common iliac vasculature, at a level just cranial to the top of the radiation treatment port. Fortuin et al [26] noted in their study that 61% of metastatic prostate cancer nodes (in the setting of BCR, before salvage RT) were located in areas outside the conventional pelvic radiation target volume, which may explain the preponderance of nodes that later present after failure of salvage RT above the treated area. Local recurrence can also be seen after failed primary treatment and subsequent failed adjuvant or salvage RT but is much less common than in Variant 1. Local ablative therapies are much less common than RP and primary RT options and make up <5% of primary treatments overall in the United States, but there is great variation in practice, and in some centers, cryoablation is the dominant treatment comprising >70% of patients [106]. Although less well studied, recurrence after ablative therapies seems to be most common locally if the disease was localized initially. CT Abdomen and Pelvis CT is not effective for detecting locally recurrent tumor in an irradiated prostate gland or after ablative therapy because of its limited soft tissue resolution within the prostate gland.


Post Treatment Follow up of Prostate Cancer. In the evaluation of nodal disease, CT heavily relies on size to detect nodal metastases, which is a significant limitation and confers mediocre sensitivity for prostate cancer nodal metastases because large numbers of metastatic nodes are known to be a normal size [26]. CT is useful in following the response of known enlarged metastatic lymphadenopathy to treatment. CT is useful in detecting sclerotic bone and visceral metastases, although bone scan and MRI are superior in the diagnosis and follow-up of bone metastases [27], and choline PET is much better for the detection and follow-up of bone metastases. As bone metastases respond to treatment, they often become more densely sclerotic, which by CT is a common pitfall falsely interpreted as progression. CT is useful when done with IV contrast for cancer detection and surveillance. There is no evidence to support use of CT without IV contrast or multiphasic scanning (ie, without and with IV contrast). CT Chest, Abdomen, and Pelvis There is rarely any indication for consideration of extension of coverage with CT of the chest for follow-up of a patient with a clinical concern for residual or recurrent disease after nonsurgical local and pelvic treatments. Additionally, there is limited evidence to support the use CT chest abdomen and pelvis in this setting. MRI Pelvis MP-MRI has shown to be helpful in the detection of local recurrence after RT, and T2-weighted imaging by itself is very limited for detection of recurrence after RT [29]. Wu et al [39] in a meta-analysis to assess the effectiveness of an MP-MRI in detecting local recurrent prostate cancer post-RT found that DCE imaging, As with Variant 1, typically in this setting, MRI is performed on the pelvis only, at least initially. Residual, recurrent, or metastatic disease is all most likely to be identified in the pelvis, and additional coverage of the abdomen is of little added value.


Post Treatment Follow up of Prostate Cancer. Overall, pelvic MRI in the setting of Variant 2 is complementary to specialized PET examinations (choline, PSMA, or fluciclovine), and both categories of examinations may be beneficial to perform. MRI Abdomen and Pelvis MRI is performed of the pelvis only, at least initially. Residual, recurrent, or metastatic disease is all most likely to be identified in the pelvis, and additional coverage of the abdomen is of little added value. Additionally, there is limited evidence to support the use of MRI abdomen and pelvis for follow-up of a patient with a clinical concern for residual or recurrent disease after nonsurgical local and pelvic treatments. TRUS Prostate Several studies have reported that TRUS is unreliable for the detection of cancer recurrence after EBRT, showing a limited sensitivity of 49% and a specificity of 57%, which is worse than DRE (sensitivity 73%, specificity 66%) [93,121]. TRUS-Guided Biopsy Prostate TRUS-guided sextant biopsy, commonly proposed as the reference standard for detection of local recurrence, may require repeated biopsies to reach a final diagnosis [122,123]. In addition to false-negative results due to sampling error, false-positive results may also occur because the presence of malignant cells in biopsy specimens may represent biologically inactive tumor remnants, especially in the first 1 to 2 years after RT [122,123]. Post-Treatment Follow-up of Prostate Cancer MRI-Targeted Biopsy Prostate Biopsy is best done when targeting suspicious lesions identified by MRI rather than as a nontargeted systematic TRUS biopsy of the region. However, because the native gland is still present, commercially available MRI-US fusion biopsy systems can be used to aid in targeting and improving biopsy accuracy. Candidacy for salvage local therapy is largely determined by identification and characterization of a treatable local recurrence by biopsy, often targeted by MRI.


Post Treatment Follow up of Prostate Cancer. Choline PET/CT Skull Base to Mid-Thigh PET with newer prostate-specific radiotracers has shown excellent performance and great potential for revolutionizing the diagnosis and, consequently, the management of patients with BCR. Choline was the first to receive FDA approval and has been extensively used and studied with several large recent meta-analyses availalable [44,45]. For example, a meta-analysis by Evangelista et al [44] found a sensitivity of 85.6% and a specificity of 92.6% for all sites of recurrence, of which there was a pooled sensitivity of 100% for lymph node metastases with a corresponding 81.8% sensitivity. Note this study combines post-RP and post-RT patients, and there is no evidence of a significant difference in performance of choline PET between these 2 scenarios. It is inferior to MRI for detection of local recurrence, but the meta-analysis still showed a 75.4% sensitivity and an 82% specificity for prostatic fossa recurrence detection. In a study of 184 primary RT patients who experienced BCR, and over half of whom had positive confirmatory biopsies of the prostate and/or distant sites, the median PSA level of those patients having a positive choline PET scan was 6.3 ng/mL with a sensitivity and specificity of 95% and 73%, respectively [124]. In another study of 41 patients who underwent salvage RT to the prostate bed only following RP and subsequent biochemical failure, choline PET scans were positive with a median PSA of 3.1 ng/mL and an interquartile range of 1.9 to 5.6 ng/mL. The vast majority of patients had disease that was found outside of the irradiated prostate bed with 61% having disease outside of the pelvis [124,125]. Bone metastasis detection and treatment response evaluation is also very good. Choline requires an on-site cyclotron for generation of the agent because of the short half-life, which restricts where it is feasible to perform.


Post Treatment Follow up of Prostate Cancer. Choline PET/MRI Skull Base to Mid-Thigh There is limited evidence to support the use of choline PET/MRI for follow-up of a patient with a clinical concern for residual or recurrent disease after nonsurgical local and pelvic treatments. Fluciclovine PET/MRI Skull Base to Mid-Thigh There is limited evidence to support the use of fluciclovine PET/MRI for follow-up of a patient with a clinical concern for residual or recurrent disease after nonsurgical local and pelvic treatments. PET Using Other Agents: There are many additional prostate-specific tracers that are not FDA approved, including 11C-acetate [70,71], 18F-choline [72-74], Bombesin, 18F-fluorodihydrotestosterone [78] that are in various stages of investigation and have been reported to detect local and metastatic recurrent disease in patients with biochemical failure after local treatment. These agents remain investigational, but some have shown excellent results and hold great potential. Fluoride PET/CT Skull Base to Mid-Thigh Fluoride PET/CT is not routinely used in the evaluation of prostate cancer recurrence. PSMA PET/CT Skull Base To Mid-Thigh PSMA was approved by FDA in December 2020 for patients with suspected prostate cancer metastasis who are potentially curable with previous surgery or RT in the University of California, Los Angeles, and the University of California, San Francisco [82]. In a study with 50 patients with BCR after RT who underwent PSMA PET/CT and salvage prostatectomy, the sensitivity and positive predictive value of PSMA PET/CT were both 100%. A separate analysis per lymph node revealed a sensitivity, specificity, positive predictive value, and negative predictive value as 34.78%, 100%, 100%, and 97.52%, respectively [129]. Radiography Skeletal Survey Radiographic survey is not routinely used in the evaluation of prostate cancer recurrence.


Post Treatment Follow up of Prostate Cancer. After an initial favorable response to ADT, a significant fraction of patients with advanced prostate cancer will develop CRPC with a median time to androgen independence of 14 to 30 months [130]. Patients invariably progress to a castration-resistant state in which the cancer will grow despite low levels of serum testosterone [131]. More than 90% of patients with CRPC have bone metastases [132]. Morbidity and mortality from prostate cancer is typically the result of metastatic CRPC. CRPC represents the lethal form of the disease and carries a poor prognosis with a median survival of <2 years for those with metastatic disease [133]. In this setting, imaging is not done for detection or diagnosis of disease, but the role shifts to one of monitoring response to therapy. Bone Scan Bone metastases are common in late-stage metastatic prostate cancer, particularly CRPC. Bone scan in this setting with PSA >60 ng/mL is greatly increased in yield compared to Variants 1 and 2. Bone scan can reflect changes in disease status post-treatment, and successfully treated metastases can become negative, which usually is accompanied by a corresponding marked decrease in serum PSA level. Bone scan can show a flare phenomenon after treatment initiation that could lead to false interpretation as progression [134]. Bone scan and CT are often performed as complimentary modalities, the pair serving as an alternative to specialized PET examinations (choline or fluciclovine). CT Chest, Abdomen, and Pelvis With advanced disease, nodal metastases progress in size and become diagnosable by CT. In this setting, CT is useful in following response of known enlarged metastatic lymphadenopathy to treatment. CT is useful in Post-Treatment Follow-up of Prostate Cancer detecting visceral metastases; liver metastases in particular are the most common visceral metastasis, and CT is very accurate for that evaluation [135].


Post Treatment Follow up of Prostate Cancer. CT is also useful in detecting sclerotic bone metastases, although bone scan and MRI are superior in the diagnosis and follow-up of bone metastases [27], and choline PET is much better for detection and follow-up of bone metastases. As bone metastases respond to treatment, they often become more densely sclerotic, which by CT is a common pitfall falsely interpreted as progression. CT is useful when done with IV contrast for cancer detection and surveillance. There is no evidence to support use of CT without IV contrast or multiphasic scanning (ie, without and with IV contrast). In the setting of metastatic disease, chest CT becomes clinically relevant and is a first-line imaging modality for detection of pulmonary metastases. Bone scan and CT are often performed as complimentary modalities, the pair serving as an alternative to specialized PET examinations (choline or fluciclovine or PSMA). CT Abdomen and Pelvis With advanced disease, nodal metastases progress in size and become diagnosable by CT. In this setting, CT is useful in following response of known enlarged metastatic lymphadenopathy to treatment. CT is useful in detecting visceral metastases; liver metastases in particular are the most common visceral metastasis, and CT is very accurate for that evaluation [135]. CT is also useful in detecting sclerotic bone metastases, although bone scan and MRI are superior in the diagnosis and follow-up of bone metastases [27], and choline PET is much better for the detection and follow-up of bone metastases. As bone metastases respond to treatment, they often become more densely sclerotic, which by CT is a common pitfall falsely interpreted as progression. CT is useful when done with IV contrast for cancer detection and surveillance. There is no evidence to support use of CT without IV contrast or multiphasic scanning (ie, without and with IV contrast).


Post Treatment Follow up of Prostate Cancer. As opposed to Variants 1 and 2 in the setting of metastatic disease, chest CT becomes clinically relevant and is a first-line imaging modality for detection of pulmonary metastases. MRI Abdomen and Pelvis Local recurrence, even if present, becomes of lesser clinical importance in this setting, unless it is locally advanced and is causing urinary or bowel complications. MRI is capable of assessing response to metastatic nodal disease similar to CT based on size, with the addition of also being able to show functional changes. Post-ADT perfusion should greatly decrease with a positive response, and apparent diffusion coefficient values typically increase. Bone metastases can be followed for response by MRI as well in a similar way. In this clinical setting, the likelihood of metastatic disease outside the pelvis is increased. For example, liver metastases and nodal metastases in higher stations are most often seen in the setting of Variant 3. It is probable that coverage of the abdomen in addition to the pelvis would provide more benefit in this setting, but evidence is lacking. MRI Pelvis In this clinical setting, the likelihood of metastatic disease outside the pelvis is increased. For example, liver metastases and nodal metastases in higher stations are most often seen in the setting of Variant 3. It is probable that coverage of the abdomen in addition to the pelvis would provide more benefit, but evidence is lacking. Local recurrence, even if present, becomes of lesser clinical importance in this setting, unless it is locally advanced and is causing urinary or bowel complications. MRI-Targeted Biopsy Prostatectomy Bed Because local recurrence is of lesser clinical importance in the setting of metastatic prostate cancer, MRI-targeted biopsy of the prostate is not routinely used for evaluation.


Post Treatment Follow up of Prostate Cancer. Choline PET/CT Skull Base to Mid-Thigh Although choline PET has been extensively used and studied, with several large meta-analyses available [44,45], the literature is less rigorous for this specific application. There are multiple studies showing its utility in this application [136-139], with no evidence that choline PET has any detriment in performance, and given that metastatic disease outside the pelvis is increased in frequency in this setting and that choline PET activity correlates well with disease activity, it likely is of increased utility for monitoring response to treatment, although there is insufficient data. There is some evidence that ADT decreases choline uptake in lesions that are not CRPC and that it is able to predict treatment response to various agents in the setting of CRPC. Choline requires an on- site cyclotron for generation of the agent because of its short half-life, which restricts where it is feasible to perform. Post-Treatment Follow-up of Prostate Cancer Choline PET/MRI Skull Base to Mid-Thigh There is limited evidence to support the use of choline PET/MRI for follow-up of a patient treated by systemic therapy. Fluoride PET/CT Skull Base to Mid-Thigh Fluoride is a tracer that has been available for clinical use for several decades, and it aims to demonstrate the increased uptake within foci in the bone with increased bone turnover in biologic processes such as metastatic involvement, fracture, or degenerative changes. Fluoride PET has a similar mechanism with bone scan; however, it is a much more sensitive imaging agent, and it offers tomographic evalaution. A recent meta-analysis revealed fluoride PET has a much higher sensitivity compared to bone scan (96% versus 86%) [140]. Another meta- analysis compared fluoride with bone scan and whole body MRI.


Post Treatment Follow up of Prostate Cancer. The results indicated that fluoride has a higher diagnostic accuracy compared to bone scan (0.97 versus 0.842), whereas the dianostic accuracy of fluoride was similar to that of whole body MRI for detecting bone lesions (0.97 versus 0.947) [141]. In addition to its use for detecting bone lesions in the setting of metastatic prostate cancer, quantitative features extracted from fluoride PET have been reported to be promising in treatment response evalaution and prognosis [141]. Although its higher sensitivity for detecting bone metastases, the actual clinical benefit of fluoride PET on patient outcomes is yet to be reported. Fluciclovine PET/CT Skull Base to Mid-Thigh Fluciclovine is FDA approved (May 2016) for imaging of prostate cancer patients with BCR, and its use in metastatic prostate cancer is not as commonly reported as in BCR naturally. There are in vitro studies and anecdotal experience suggesting the potential utility with CRPC [142-144]. In a recent study with 106 patients, fluciclovine PET/CT was compared with bone scan for detecting bone metastases. The sensitivity, specificity, positive predictive value, and negative predictive value for bone scan were 79%, 86%, 45%, and 96%, respectively, whereas corresponding performance metrics for fluciclovine PET/CT were 100%, 98%, 89%, and 100%, respectively [145]. Fluciclovine PET/MRI Skull Base to Mid-Thigh There is limited evidence to support the use of fluciclovine PET/MRI for follow-up of a patient treated by systemic therapy. A small study of patients with primary prostate cancer treated with ADT reported a decrease in radiotracer uptake in local and metastatic lesions on PET/MRI [146].


Post Treatment Follow up of Prostate Cancer. PET Using Other Agents: There are many additional prostate-specific tracers that are not FDA approved, including 11C-acetate [70,71], 18F-choline [72-74], Bombesin, 18F-fluorodihydrotestosterone [78], and a family of related PSMA tracers [76,77,140], that are in various stages of investigation and have been reported to detect local and metastatic recurrent disease in patients with biochemical failure after local treatment. These agents remain investigational, but some have shown excellent results and hold great potential. FDG-PET/CT FDG is an inferior tracer to choline and other prostate-specific agents [79,80,147-149] and has limited use in standard practice. However, as advanced metastatic prostate cancer migrates to a high Gleason grade, dedifferentiates, or transforms to other aggressive variants, such as small cell type, the tumor cells are more likely to convert to a higher glucose metabolism, and FDG can become useful in the detection and monitoring of this subset of patients, although the literature data are limited [150-152]. PSMA PET/CT Skull Base To Mid-Thigh PSMA was FDA approved in December 2020 for imaging of prostate cancer patients with BCR, and its use in metastatic prostate cancer is not as commonly reported as in BCR, and it is mostly limited to research use. In 1 study that compared visual and semiautomatic bone scan evaluations with PSMA PET/CT in 30 patients, visual and semiautomatic bone scan evaluation showed similar results with an average of 19.4 and 17.8 detected bone lesion per patient, whereas PSMA PET/CT revealed 40 lesions per patient [153]. In a study with 51 patients who had inconclusive F-18-NaF PET/CT findings for bone metastases, additional PSMA PET/CT ultimately diagnosed bone metastases in 13 patients (25% of the entire cohort). Patient-based sensitivity, specificity, and accuracy of additional PSMA PET/CT were 100%, 95%, and 96%, respectively [154].


Post Treatment Follow up of Prostate Cancer. PSMA PET/CT has the potential to estimate tumor burden in metastatic prostate cancer for selecting patients who may benefit from PSMA radioligand therapies. For this purpose, the actual relationship between alterations in PSMA expression and PSMA uptake at PET/CT imaging versus ADT treatment status is yet to be reported. Post-Treatment Follow-up of Prostate Cancer DCFPyL PET/CT Skull Base To Mid-Thigh DCFPyL PET/CT was FDA approved in May 2021 for imaging of prostate cancer patients with BCR, and its use in metastatic prostate cancer is not routine clinically and is confined to research. In 1 prospective study with 15 patients with metastatic prostate cancer, DCFPyL PET/CT was compared with F-18-NaF PET/CT for detection of bone lesions. Results of this study revealed 405 bone lesions suggestive of sites of prostate cancer were identified on at least one scan. On DCFPyL PET/CT, 391 (96.5%) were definitively positive, 4 (1.0%) were equivocally positive, and 10 (2.5%) were negative. Whereas on F-18-NaF PET/CT, the corresponding values were 388 (95.8%), 4 (1.0%), and 13 (3.2%), respectively. Of the definitively negative lesions on DCFPyL PET/CT, 8 of 10 (80.0%) were sclerotic, and 2 of 10 (20.0%) were infiltrative or marrow-based. Additionally, 12 of 13 (92.3%) of the definitively negative lesions on F-18-NaF PET/CT were infiltrative or marrow-based, and 1 of 13 (7.7%) was lytic. Both tracers had similar sensitivities for detecting bone lesions in metastatic prostate cancer patients [155]. In a limited number of studies, utility of DCFPyL PET/CT is evaluated for therapeutic response to ADT in metastatic prostate cancer patients. In a prospective study with 6 patients with metastatic castration resistant prostate cancer, DCFPyL PET/CT was used at baseline and 3 months after treatment to monitor the therapy response to bipolar ADT. Results revealed that 3 of 6 (50%) patients had progression on DCFPyL PET/CT.


Imaging after Breast Surgery

Imaging after Breast Surgery.  OR Discussion of Procedures by Variant Variant 1: Female. Age 40 years or older. Postsurgical excision with nonmalignant pathology. Asymptomatic. Initial imaging. Benign breast disease can be classified into 3 broad categories: nonproliferative lesions, proliferative lesions without atypia, and proliferative lesions with atypia. Nonproliferative lesions include benign calcifications, fibrocystic changes, fibroadenomas, lipomas, fat necrosis, and nonsclerosing adenosis. Proliferative lesions without atypia include usual ductal hyperplasia, sclerosing adenosis, complex fibroadenomas, radial scars/complex sclerosing lesions, papillomas, and papillomatosis. Proliferative lesions with atypia include atypical ductal hyperplasia, atypical lobular hyperplasia, lobular carcinoma in situ (LCIS), and flat epithelial atypia [4,5]. Benign breast disease and breast tissue density are independent risk factors for developing breast cancer [5,6]. One study of women from the Breast Cancer Surveillance Consortium (BCSC) reported breast cancer in 25% of women with excision for aUMass Memorial Medical Center, Worchester, Massachusetts. bPanel Chair, Alpert Medical School of Brown University, Providence, Rhode Island. cPanel Vice-Chair, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida. dWashington University School of Medicine, Saint Louis, Missouri. eUniversity of Cincinnati, Cincinnati, Ohio. fPenn State Health Hershey Medical Center, Hershey, Pennsylvania. gUniversity of Utah, Salt Lake City, Utah. hKaiser Permanente, Atlanta, Georgia. iMemorial Sloan Kettering Cancer Center, New York, New York. jUniversity of Michigan, Ann Arbor, Michigan. kSt. Bernards Healthcare, Jonesboro, Arkansas. lDuke Signature Care, Durham, North Carolina; American College of Physicians. mPrinceton Community Hospital, Princeton, West Virginia; American College of Surgeons. nProMedica Breast Care, Toledo, Ohio. oEmory University Hospital, Atlanta, Georgia; RADS Committee.


Imaging after Breast Surgery

Imaging after Breast Surgery. pHoag Family Cancer Institute, Newport Beach, California and University of Southern California, Los Angeles, California; Commission on Nuclear Medicine and Molecular Imaging. qSpecialty Chair, NYU Clinical Cancer Center, New York, New York. Reprint requests to: publications@acr.org Imaging after Breast Surgery proliferative lesions with atypia [7]. Almost 30% of women with breast cancer have a history of benign breast disease [4]. Although there are no relevant studies examining mammographic follow-up intervals of benign breast disease following surgical biopsy, there are some studies examining imaging intervals following benign core biopsy. In populations with nonproliferative lesions or proliferative lesions without atypia, imaging intervals of 6 months compared to routine annual screening did not improve cancer detection rates or change invasive cancer rates, stage, tumor size, or nodal status [11,12]. The studies on proliferative lesions with atypia, examining the need for excision and, if not excised, need for short interval follow-up, are varied [13-16] and are outside the scope of this document. Atypical ductal hyperplasia on core biopsy typically warrants surgical consultation and/or multidisciplinary discussion regarding the benefits and risks of subsequent excision. There is more varied practice in management of atypical lobular hyperplasia, LCIS, and flat epithelial atypia found on core biopsy. One study of more than 2 million screening mammograms in nearly 800,000 women, with 15% having a self- reported history of prior benign percutaneous or excisional breast biopsy, showed no difference in mammographic sensitivity; however, there was decreased specificity and mammographic performance, which was attributed to tissue characteristics rather than the biopsy itself [18].


Imaging after Breast Surgery

Imaging after Breast Surgery. Another study comparing patients with history of proliferative lesions with atypia with matched screenings based on age, density, and breast cancer family history also found no differences in mammographic sensitivity or proportion of interval cancers; however, they also reported lower specificity in the atypical proliferative lesions group [19]. FDG-PET Breast Dedicated There is no relevant literature to support the use of fluorine-18-2-fluoro-2-deoxy-D-glucose (FDG)-PET breast imaging in this clinical scenario. Although there are no relevant studies examining mammographic follow-up intervals of benign breast disease following surgical biopsy, there are some studies examining imaging intervals following benign core biopsy. In populations with nonproliferative lesions or proliferative lesions without atypia, imaging intervals of 6 months compared with routine annual screening did not improve cancer detection rates or change invasive cancer rates, stage, tumor size, or nodal status [11,12]. The studies on proliferative lesions with atypia, examining the need for Imaging after Breast Surgery excision and, if not excised, the need for short interval follow-up, are varied [13-16,20] and are outside the scope of this document. A majority agree that there is a need for surgical excision when atypical ductal hyperplasia is found on core biopsy. There is more varied practice in management of atypical lobular hyperplasia, LCIS, and flat epithelial atypia found on core biopsy. One study of more than 2 million screening mammograms in nearly 800,000 women, with 15% having a self- reported history of prior benign percutaneous or excisional breast biopsy, showed no difference in mammographic sensitivity; however, there was decreased in specificity and mammographic performance, which was attributed to tissue characteristics rather than the biopsy itself [18].


Imaging after Breast Surgery

Imaging after Breast Surgery. Another study comparing patients with history of proliferative lesions with atypia with matched screenings based on age, density, and breast cancer family history also found no differences in mammographic sensitivity or proportion of interval cancers; however, they also reported lower specificity in the atypical proliferative lesions group [19]. MRI Breast Without IV Contrast There is no relevant literature to support the use of MRI breast without IV contrast for screening in this clinical scenario. Sestamibi MBI There is no relevant literature to support the use of Tc-99m sestamibi molecular breast imaging (MBI) in this clinical scenario. Variant 2: Female. Age 30 to 39 years. Postsurgical excision with nonmalignant pathology. Asymptomatic. Initial imaging. Benign breast disease can be classified into 3 broad categories: nonproliferative lesions, proliferative lesions without atypia, and proliferative lesions with atypia. Nonproliferative lesions include benign calcifications, fibrocystic changes, fibroadenomas, lipomas, fat necrosis, and nonsclerosing adenosis. Proliferative lesions without atypia include usual ductal hyperplasia, sclerosing adenosis, complex fibroadenomas, radial scars/complex sclerosing lesions, papillomas, and papillomatosis. Proliferative lesions with atypia include atypical ductal hyperplasia, atypical lobular hyperplasia, LCIS, and flat epithelial atypia [4,5]. Benign breast disease and breast tissue density are independent risk factors for developing breast cancer [5,6]. One study of women from the BCSC reported breast cancer in 25% of women with excision for proliferative lesions with atypia [7]. Almost 30% of women with breast cancer have a history of benign breast disease [4]. Imaging after Breast Surgery FDG-PET Breast Dedicated There is no relevant literature to support the use of FDG-PET breast in this clinical scenario.


Imaging after Breast Surgery

Imaging after Breast Surgery. MRI Breast Without IV Contrast There is no relevant literature to support the use of MRI breast without IV contrast for screening in this clinical scenario. Sestamibi MBI There is no relevant literature to support the use of Tc-99m sestamibi MBI in this clinical scenario. Imaging after Breast Surgery Variant 3: Adult female younger than 30 years of age. Postsurgical excision with nonmalignant pathology. Asymptomatic. Initial imaging. Benign breast disease can be classified into 3 broad categories: nonproliferative lesions, proliferative lesions without atypia, and proliferative lesions with atypia. Nonproliferative lesions include benign calcifications, fibrocystic changes, fibroadenomas, lipomas, fat necrosis, and nonsclerosing adenosis. Proliferative lesions without atypia include usual ductal hyperplasia, sclerosing adenosis, complex fibroadenomas, radial scars/complex sclerosing lesions, papillomas, and papillomatosis. Proliferative lesions with atypia include atypical ductal hyperplasia, atypical lobular hyperplasia, LCIS, and flat epithelial atypia [4,5]. Benign breast disease and breast tissue density are independent risk factors for developing breast cancer [5,6]. One study of women from the BCSC reported breast cancer in 25% of women with excision for proliferative lesions with atypia [7]. Almost 30% of women with breast cancer have a history of benign breast disease [4]. FDG-PET Breast Dedicated There is no relevant literature to support the use of FDG-PET breast in this clinical scenario. MRI Breast Without and With IV Contrast There is no relevant literature to support the routine use of MRI breast without and with IV contrast in an average- risk patient. Some benign breast disease, especially atypical ductal hyperplasia and lobular neoplasia can increase Imaging after Breast Surgery MRI Breast Without IV Contrast There is no relevant literature to support the use of MRI breast without IV contrast for screening in this clinical scenario.


Imaging after Breast Surgery

Imaging after Breast Surgery. Sestamibi MBI There is no relevant literature to support the use of Tc-99m sestamibi MBI in this clinical scenario. Variant 4: Adult female. Postsurgical excision for breast cancer. Positive margins. Asymptomatic. Initial imaging. Margin status is an important predictor of local recurrence of invasive or in situ cancer after breast conservation surgery. For invasive breast cancer (with or without DCIS), a negative margin is defined as no tumor on ink by histology. In contrast, guidelines recommend that margins for pure DCIS (with or without microinvasion) be at least 2 mm [21]. Frequencies of positive margins after initial surgery vary based on multiple factors including type of breast cancer, appearance on imaging, breast density, and surgical technique. Positive margins at first surgery and at final breast surgery are predictors of breast cancer recurrence [23]. The goal of surgery is to remove the tumor and obtain negative margins. Re-excision is usually performed in the setting of positive margins, often without additional imaging evaluation. Imaging is sometimes used to help delineate residual disease before re-excision. Sometimes despite re-excision, margins remain close or positive. Digital Breast Tomosynthesis Diagnostic There is no relevant literature to support the routine use of diagnostic DBT in this clinical scenario. When diagnostic mammography is performed in this scenario, it is typically for evaluation of residual calcifications, which are better visualized on magnification mammograms rather than DBT. One small retrospective study evaluated postexcision mammography and MRI to assess for residual disease. Of 51 patients with malignant calcifications (32 with and 19 without residual disease), mammography sensitivity, specificity, and accuracy were 78.1%, 42.1%, and 62.7%, respectively.


Imaging after Breast Surgery

Imaging after Breast Surgery. MRI was better than mammography, especially in the setting of low background parenchymal enhancement, in which sensitivity, specificity, and accuracy were 88.8%, 57.1%, and 76.5%, respectively [24]. Another small single institution study of 281 patients with ductal carcinoma in situ, of which 144 underwent postexcision preirradiation mammography, found postexcision preirradiation mammography resulted in a change in surgical management in 7% (10/144) and removal of residual ductal carcinoma in situ in 4% (6/144) of patients. More importantly there was no significant change in 10-year local recurrence-free survival (95% versus 92%, with and without postexcision preirradiation mammography) [25]. Digital Breast Tomosynthesis Screening There is no relevant literature to support the use of screening DBT in this clinical scenario. FDG-PET Breast Dedicated There is no relevant literature to support the use of FDG-PET breast in this clinical scenario. Imaging after Breast Surgery Mammography Diagnostic There is insufficient evidence to support the routine use of diagnostic mammography in this clinical scenario. However, it can be helpful in a subset of patients in which there is concern for residual microcalcifications, which are better visualized on magnification mammograms rather than DBT. One small retrospective study evaluated postexcision mammography and MRI to assess for residual disease. Of 51 patients with malignant calcifications (32 with and 19 without residual disease), mammography sensitivity, specificity, and accuracy were 78.1%, 42.1%, and 62.7%, respectively. MRI was better than mammography, especially in the setting of low background parenchymal enhancement, in which sensitivity, specificity, and accuracy were 88.8%, 57.1%, and 76.5%, respectively [24].


Imaging after Breast Surgery

Imaging after Breast Surgery. Another small single institution study of 281 patients with ductal carcinoma in situ, of which 144 underwent postexcision preirradiation mammography, found postexcision preirradiation mammography resulted in a change in surgical management in 7% (10/144) and removal of residual ductal carcinoma in situ in 4% (6/144) of patients. More importantly there was no significant change in 10-year local recurrence-free survival (95% versus 92%, with and without postexcision preirradiation mammography) [25]. Mammography Screening There is no relevant literature to support the use of screening mammography in this clinical scenario. MRI Breast Without and With IV Contrast There is insufficient evidence to support the routine use of MRI breast without and with IV contrast in this clinical scenario. MRI, when performed, is generally done before initial surgery. However, it may be performed following initial surgery in the setting of unsuspected positive margins. Evaluating residual disease in the surgical cavity is limited with MRI because of associated benign enhancement of the borders of the resection cavity obscuring residual disease. MRI may be helpful in identification of more widespread disease or remote disease [26,27]. This information can guide surgical planning for re-excision or need for mastectomy. One small retrospective study evaluated postexcision mammography and MRI to assess for residual disease in 51 patients with malignant calcifications (32 with and 19 without residual disease). MRI was better than mammography, especially in the setting of low background parenchymal enhancement, where sensitivity, specificity, and accuracy were 88.8%, 57.1%, and 76.5%, respectively. However higher background parenchymal enhancement did reduce sensitivity and accuracy [24]. MRI Breast Without IV Contrast There is no relevant literature to support the use of MRI breast without IV contrast for screening in this clinical scenario.


Imaging after Breast Surgery

Imaging after Breast Surgery. Sestamibi MBI There is no relevant literature to support the use of Tc-99m sestamibi MBI in this clinical scenario. US Breast There is no relevant literature to support the use of breast US in this clinical scenario. Variant 5: Adult female. Surveillance following completion of breast conservation therapy for breast cancer. Negative margins. With or without radiation. Asymptomatic. Margin status is an important predictor of local recurrence of invasive or in situ cancer after breast conservation surgery. For invasive breast cancer (with or without DCIS), a negative margin is defined as no tumor on ink by histology. The aim of surveillance in patients after primary breast cancer treatment is to detect local recurrence and/or second breast cancers before symptoms develop. Women with a personal history of breast cancer develop a second breast cancer at a rate of 5% to 10% within 5 to 10 years after initial diagnosis [28-30]. Factors predicting risk of locoregional recurrence include age, tumor grade and size, multifocality, nodal involvement, receptor status, and whether the patient received radiotherapy, chemotherapy, or hormonal therapy [31-33]. Interval breast cancers have been reported in 24% to 30% with mammographic surveillance [34-36], and 7% with the use of multimodality imaging with mammography, US, and MRI [37]. Interval cancers are more likely to occur in women <40 to 50 years of age, in those with primary cancers that are negative estrogen receptor/progesterone receptor (ER/PR) or triple negative (negative ER/PR and negative HER2), in those with primary cancers being interval cancers, in patients with history of breast conservation therapy without radiation, and in women with dense breast tissue [35,36,38,39]. These patients may benefit from supplemental screening. Please refer to the ACR Imaging after Breast Surgery


Imaging after Breast Surgery

Imaging after Breast Surgery. Digital Breast Tomosynthesis Diagnostic Annual mammography is the best imaging test for surveillance in this clinical scenario, with reduction of mortality compared with women with history of breast cancer who do not get annual mammography [40,41]. The most common presentation of a recurrent or second breast cancer in patients with a personal history of breast cancer is an abnormal mammogram in an otherwise asymptomatic patient [22,34,36]. This ACR practice parameter allows asymptomatic women with a personal history of breast cancer to undergo diagnostic mammography [42]. A survey of radiologists showed variability in recommendation of diagnostic versus screening mammography for women treated with breast conservation therapy. Most (79%) recommended at least 1 diagnostic mammogram, with 49% recommending diagnostic mammography up to 2 years and 33% recommending diagnostic mammography from 2 to 5 years [43]. This is supported by the fact that most locoregional recurrences occur within 5 years after diagnosis [34,35,44], with recurrence risk greatest 2 to 3 years after initial therapy [23,28,33,37]. There is suboptimal compliance of annual mammography in select patients with a history of breast cancer. Groups most impacted are younger women <45 to 50 years of age, older women >65 years of age, African Americans and other underrepresented minorities, and women who did not have a recent physician visit [34,45-50]. The American Society of Radiology Oncology (ASTRO) and National Comprehensive Cancer Network (NCCN) both recommend annual mammographic surveillance for women who have completed radiation therapy as part of breast conservation therapy, with the first imaging performed at 6 to 12 months [51,52]. Other studies have found imaging before 12 months is not beneficial and/or leads to unnecessary additional imaging because of acute breast changes, supporting the first mammogram to be at 12 months after the last mammogram [30,53-56].


Imaging after Breast Surgery

Imaging after Breast Surgery. More frequent imaging of the ipsilateral affected breast beyond annual surveillance mammography, at 6-month intervals for the first 2 to 5 years, has also been studied. Two groups showed no benefits to this more frequent imaging [30,56]. One study found lower stage of recurrence in women undergoing 6-month surveillance compared with annual surveillance; however, this may be secondary to decreased compliance with imaging recommendations in the annual surveillance group and follow-up was insufficient to assess for any mortality differences [57]. The addition of DBT to 2-D digital mammography or 2-D synthetic images in the surveillance of patients with prior breast cancer history has been shown to reduce recall rates and indeterminate findings [58-61], without significant change in cancer detection rate [60,61]. Digital Breast Tomosynthesis Screening Annual mammography is the best imaging test for surveillance in this clinical scenario, with reduction of mortality compared with women with history of breast cancer who do not get annual mammography [40,41]. The most common presentation of a recurrent or second breast cancer in patients with a personal history of breast cancer is an abnormal mammogram in an otherwise asymptomatic patient [22,34,36]. The ACR practice parameters state asymptomatic women previously treated for breast cancer may undergo annual screening or diagnostic mammography, as determined by the imaging facility [42]. The most common factor influencing this decision is the number of years since cancer diagnosis and treatment. A survey of radiologists showed variability in recommendation of diagnostic versus screening mammography for women treated with breast conservation therapy. Most (79%) recommended at least 1 diagnostic mammogram, with 49% recommending diagnostic mammography up to 2 years and 33% recommending diagnostic mammography from 2 to 5 years [43].


Imaging after Breast Surgery

Imaging after Breast Surgery. This is supported by the fact that most locoregional recurrences occur within 5 years after diagnosis [34,35,44], with recurrence risk greatest 2 to 3 years after initial therapy [23,28,33,37]. There is suboptimal compliance of annual screening mammography in select patients with a history of breast cancer. Groups most impacted are younger women <45 to 50 years of age, older women >65 years of age, African Americans and other underrepresented minorities, and women who did not have a recent physician visit [34,45-50]. The ASTRO and NCCN guidelines both recommend annual mammographic surveillance for women who have completed radiation therapy as part of breast conservation therapy, with the first imaging performed at 6 to 12 months [51,52]. Other studies have found imaging before 12 months is not beneficial and/or leads to unnecessary additional imaging due to acute breast changes, supporting the first mammogram to be at 12 months after the last mammogram [30,53-56]. Imaging after Breast Surgery More frequent imaging of the ipsilateral affected breast beyond annual surveillance mammography, at 6-month intervals for the first 2 to 5 years, has also been studied. Two groups showed no benefits to this more frequent imaging [30,56]. One study found lower stage of recurrence in women undergoing 6-month surveillance compared to annual surveillance; however, this may be secondary to decreased compliance with imaging recommendations in the annual surveillance group and follow-up was insufficient to assess for any mortality differences [57]. The addition of DBT to 2-D digital mammography or 2-D synthetic images in the surveillance of patients with prior breast cancer history has been shown to reduce recall rates and indeterminate findings [58-61], without significant change in cancer detection rate [60,61]. FDG-PET Breast Dedicated There is no relevant literature to support the use of FDG-PET breast in this clinical scenario.


Imaging after Breast Surgery

Imaging after Breast Surgery. Mammography Diagnostic Annual mammography is the best imaging test for surveillance in this clinical scenario, with reduction of mortality compared to women with history of breast cancer who do not get annual mammography [40,41]. The most common presentation of a recurrent or second breast cancer in patients with a personal history of breast cancer is an abnormal mammogram in an otherwise asymptomatic patient [22,34,36]. The ACR practice parameters allows asymptomatic women with a personal history of breast cancer to undergo diagnostic mammography [42]. A survey of radiologists showed variability in recommendation of diagnostic versus screening mammography for women treated with breast conservation therapy. Most (79%) recommended at least 1 diagnostic mammogram, with 49% recommending diagnostic mammography up to 2 years and 33% recommending diagnostic mammography from 2 to 5 years [43]. This is supported by the fact that most locoregional recurrences occur within 5 years after diagnosis [34,35,44], with recurrence risk greatest 2 to 3 years after initial therapy [23,28,33,37]. There is suboptimal compliance of annual mammography in select patients with a history of breast cancer. Groups most impacted are younger women <45 to 50 years of age, older women >65 years of age, African Americans and other underrepresented minorities, and women who did not have a recent physician visit [34,45-50]. The ASTRO and NCCN guidelines both recommend annual mammographic surveillance for women who have completed radiation therapy as part of breast conservation therapy, with the first imaging performed at 6 to 12 months [51,52]. Other studies have found imaging before 12 months is not beneficial and/or leads to unnecessary additional imaging due to acute breast changes, supporting the first mammogram to be at 12 months after the last mammogram [30,53-56].


Imaging after Breast Surgery

Imaging after Breast Surgery. More frequent imaging of the ipsilateral affected breast beyond annual surveillance mammography, at 6-month intervals for the first 2 to 5 years, has also been studied. Two groups showed no benefits to this more frequent imaging [30,56]. One study found a lower stage of recurrence in women undergoing 6-month surveillance compared with annual surveillance; however, this may be secondary to decreased compliance with imaging recommendations in the annual surveillance group, and follow-up was insufficient to assess for any mortality differences [57]. The addition of DBT to 2-D digital mammography or 2-D synthetic images in the surveillance of patients with prior breast cancer history has been shown to reduce recall rates and indeterminate findings [58-61], without significant change in cancer detection rate [60,61]. Mammography Screening Annual mammography is the best imaging test for surveillance in this clinical scenario, with reduction of mortality compared with women with history of breast cancer who do not get annual mammography [40,41]. The most common presentation of a recurrent or second breast cancer in patients with a personal history of breast cancer is an abnormal mammogram in an otherwise asymptomatic patient [22,34,36]. The ACR practice parameters state asymptomatic women previously treated for breast cancer may undergo annual screening or diagnostic mammography, as determined by the imaging facility [42]. The most common factor influencing this decision is the number of years since cancer diagnosis and treatment. A survey of radiologists showed variability in recommendation of diagnostic versus screening mammography for women treated with breast conservation therapy. Most (79%) recommended at least 1 diagnostic mammogram, with 49% recommending diagnostic mammography up to 2 years and 33% recommending diagnostic mammography from 2 to 5 years [43].


Imaging after Breast Surgery

Imaging after Breast Surgery. Most locoregional recurrences occur within 5 years after diagnosis [34,35,44], with recurrence risk greatest 2 to 3 years after initial therapy [23,28,33,37]. Imaging after Breast Surgery There is suboptimal compliance of annual screening mammography in select patients with a history of breast cancer. Groups most impacted are younger women <45 to 50 years of age, older women >65 years of age, African Americans and other underrepresented minorities, and women who did not have a recent physician visit [34,45-50]. The ASTRO and NCCN guidelines both recommend annual mammographic surveillance for women who have completed radiation therapy as part of breast conservation therapy, with the first imaging performed at 6 to 12 months [51,52]. Other studies have found imaging before 12 months is not beneficial and/or leads to unnecessary additional imaging due to acute breast changes, supporting the first mammogram to be at 12 months after the last mammogram [30,53-56]. More frequent imaging of the ipsilateral affected breast beyond annual surveillance mammography, at 6-month intervals for the first 2 to 5 years, has also been studied. Two groups showed no benefits to this more frequent imaging [30,56]. One study found lower stage of recurrence in women undergoing 6-month surveillance compared with annual surveillance; however, this may be secondary to decreased compliance with imaging recommendations in the annual surveillance group and follow-up was insufficient to assess for any mortality differences [57]. The addition of DBT to 2-D digital mammography or 2-D synthetic images in the surveillance of patients with prior breast cancer history, has been shown to reduce recall rates and indeterminate findings [58-61], without significant change in cancer detection rate [60,61]. MRI Breast Without and With IV Contrast There is insufficient literature to support the routine use of MRI breast without and with IV contrast in this clinical scenario.


Imaging after Breast Surgery

Imaging after Breast Surgery. The utility for breast MRI surveillance in patients with a personal history of breast cancer depends upon associated risk factors of the studied populations, as well as institutional protocols. The ACR recommends annual breast MRI surveillance for any woman with a lifetime risk of breast cancer of ~20% or greater [8,10]. Annual breast MRI is recommended for women with a personal history of breast cancer and dense breasts as well as women diagnosed with breast cancer before 50 years of age [10], because these risk factor combinations likely result in a ~20% or greater estimated lifetime risk of developing breast cancer [10,62,63]. Annual breast MRI is also recommended for women with a mammographically occult primary breast cancer [62,63]. A large observational study from BCSC data of 812,164 women compared mammographic and MRI performance in women with and without a personal history of breast cancer. They found MRI was more likely to be performed in patients with a family history of breast cancer and personal history of breast cancer and in women with dense breast tissue. There were higher biopsy rates with MRI (6.3%) compared with mammography (2.2%), with lower cancer yield (19.5% versus 34.7%, respectively) [64]. The findings of higher cancer detection rates with MRI compared with mammography, with lower specificity and positive predictive value were confirmed [65,66]. Another large community-based study from BCSC data of 13,266 women with a personal history of breast cancer compared surveillance with MRI and mammography to mammography alone. The group with breast MRI had higher biopsy rates (odds ratio, 2.2) and cancer detection rates (odds ratio, 1.7), with no significant difference in sensitivity or interval cancers. This study did not control for confounders and suggested subgroup analysis was warranted to better delineate risks and benefits of breast MRI in this patient population [67].


Sepsis

Sepsis.  Introduction/Background According to the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3), sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection [1]. Therefore, what differentiates sepsis from simple infection is the presence of an aberrant host response to the underlying infection and the presence of organ dysfunction. When unexplained organ dysfunction is present, a search for possible causes of infection should commence, and radiological imaging is an integral part of this investigation. In 2017, the global incidence of sepsis was estimated to be 48.9 million cases with 11 million sepsis-related deaths (accounting for nearly 20% of all global deaths) [2]. Within the United States, according to the Centers for Disease Control and Prevention, the incidence of sepsis is >1.7 million adults per year. Greater than 15% of Americans diagnosed with sepsis die as a result of sepsis each year, and the in-hospital mortality is >30%, exemplifying that prompt recognition and treatment is crucial. Furthermore, sepsis was shown to account for 5.2% of total United States hospital costs (>20 billion dollars) in 2011, and the incidence is only rising because of an aging population [3,4]. Risk factors for the development of sepsis overlap with risk factors for infection and include immune compromise, chronic diseases such as malignancy, certain patient demographics (infants and elderly persons, males, Black race), as well as numerous unidentified causes [5]. This ACR Appropriateness Criteria on Sepsis focuses on thoracic and abdominopelvic causes of sepsis. Other causes of sepsis such as osteomyelitis, diabetic foot infections, periprosthetic infections, and cardiovascular infections (including endocarditis and those due to implantable devices) are not addressed. OR aPortland VA Healthcare System and Oregon Health & Science University, Portland, Oregon. bOregon Health & Science University, Portland, Oregon.


Sepsis

Sepsis. cThe University of Texas MD Anderson Cancer Center, Houston, Texas. dPanel Chair, University of Kansas Medical Center, Kansas City, Kansas. ePanel Chair, Lauderdale Radiology Group, Florence, Alabama. fPanel Chair, UT Southwestern Medical Center, Dallas, Texas. gNational Jewish Health, Denver, Colorado. hUT Southwestern Medical Center, Dallas, Texas. iThe University of Texas MD Anderson Cancer Center, Houston, Texas. jDuke University Medical Center, Durham, North Carolina. kCreighton University School of Medicine, Omaha, Nebraska. lThe University of Chicago Medical Center, Chicago, Illinois; American College of Physicians. mMedstar Washington Hospital Center, Washington, District of Columbia; American College of Chest Physicians. nUT Southwestern Medical Center, Dallas, Texas; Commission on Nuclear Medicine and Molecular Imaging. oMayo Clinic Florida, Jacksonville, Florida. pBrigham & Women's Hospital, Boston, Massachusetts. qUniversity of Illinois at Chicago College of Medicine, Chicago, Illinois; American College of Physicians. rNew York University Langone Medical Center, New York, New York. sThe University of Texas MD Anderson Cancer Center, Houston, Texas. tBrigham & Women's Hospital, Boston, Massachusetts; Committee on Emergency Radiology-GSER. uSpecialty Chair, Northwestern University, Chicago, Illinois. vSpecialty Chair, Johns Hopkins University School of Medicine, Baltimore, Maryland. wSpecialty Chair, University of Chicago, Chicago, Illinois. The American College of Radiology seeks and encourages collaboration with other organizations on the development of the ACR Appropriateness Criteria through representation of such organizations on expert panels. Participation on the expert panel does not necessarily imply endorsement of the final document by individual contributors or their respective organization. Reprint requests to: publications@acr.org Sepsis Discussion of Procedures by Variant Variant 1: Suspected or confirmed sepsis. Cough or dyspnea or chest pain. Initial imaging.


Sepsis

Sepsis. CT plays an important role in the evaluation of patients with suspected sepsis because of its high positive predictive value (PPV) [6]. When performed as either an initial or follow-up imaging study, CT often leads to a change in management [7]. CT Chest With IV Contrast Pohlan et al [6] performed a retrospective study of 357 emergency department (ED) patients with suspected sepsis, of which 132 underwent CT scan within 72 hours of admission. The most commonly identified source of infection, which the authors refer to as septic foci, was in the chest (pneumonia) reported in 38.6% (49/127) of patients. A PPV of 81.82% (confidence interval [CI], 76.31%-86.28%) was calculated for septic foci identified by CT. However, the negative predictive value (NPV) was only 21.74% (CI, 10.73%-39.11%). Patients with suspected sepsis who received a CT within 72 hours of admission were given a final diagnosis of sepsis in 93.3% of cases (124/132). The detection of septic foci in 76.5% of CTs results in a high diagnostic yield for CT in septic ED patients, particularly in patients who are extremely ill and/or require intensive care unit (ICU) admission. Just et al [7] performed a single-center 1 year retrospective study of all CT scans of the chest, abdomen, or both ordered in pursuit of suspected infection in surgical ICU patients. A source of infection was found in 76/144 of cases (52.8%) and resulted in a change of management in 65/144 (45%) of patients, including a change in antimicrobial regimen, surgery, and nonsurgical interventions such as placement of drainage catheters. A pathologic infectious source was found in the chest in 72% of patients who underwent chest CT. Use of intravenous (IV) contrast was not specified, and preceding diagnostic procedures including chest radiography were not recorded. CT Chest Without and With IV Contrast There are no data to support the use of any added value of a CT chest without IV contrast immediately before acquisition of a contrast-enhanced CT in the diagnosis of sepsis.


Sepsis

Sepsis. FDG-PET/CT Skull Base to Mid-Thigh There are no data to support the use of fluorine-18-2-fluoro-2-deoxy-D-glucose (FDG)-PET/CT as an initial diagnostic imaging study in the diagnosis of sepsis. MRI Chest Without and With IV Contrast Although MRI can readily detect pulmonary and pleural infections, there are no data to support the use of MRI chest without and with IV contrast as an initial diagnostic imaging study in the diagnosis of sepsis. MRI Chest Without IV Contrast Although MRI can readily detect pulmonary and pleural infections, there are no data to support the use of MRI chest without IV contrast as an initial diagnostic imaging study in the diagnosis of sepsis. Radiography Chest Chest radiography is a commonly obtained study in the ED because of its portability and rapid acquisition. Additionally, it has the potential of providing valuable information as an initial screening tool for infection/pneumonia, particularly in patients with sepsis who may not be able to provide a history. Furthermore, chest radiography is commonly obtained in septic patients for evaluation of adequate placement of external devices, such as endotracheal tubes and central venous catheters, at which time radiologists can concurrently evaluate for an underlying source of infection. Capp et al [8] performed a retrospective study of ED patients admitted to the ICU with the diagnosis of severe sepsis or septic shock over a 12 month period and evaluated the accuracy of chest radiography in the diagnosis of pneumonia. Of 1,400 patients admitted to the ICU, 170 met criteria for severe sepsis or septic shock, and 85 were diagnosed with pneumonia. The sensitivity and specificity of initial chest radiography was 58% (95% CI, 46%- 68%) and 91% (95% CI, 81%-95%), respectively, for the diagnosis of pneumonia. Sepsis Variant 2: Suspected or confirmed sepsis. Cough or dyspnea or chest pain. Normal or equivocal or nonspecific chest radiograph. Next imaging study.


Sepsis

Sepsis. CT plays an important role in the evaluation of patients with suspected sepsis because of its high PPV [6] when performed as either an initial or follow-up imaging study and which often leads to a change in management [7]. Septic foci are most commonly detected in the chest, abdomen, or pelvis. CT Chest With IV Contrast Pohlan et al [6] performed a retrospective study of 357 ED patients with suspected sepsis, of whom 132 underwent CT scan within 72 hours of admission. The most commonly identified source of infection, which the authors refer to as septic foci, was in the chest (pneumonia) reported in 38.6% (49/127) of patients. A PPV of 81.82% (CI, 76.31%-86.28%) was calculated for septic foci identified by CT. However, the NPV was only 21.74% (CI, 10.73%- 39.11%). Patients with suspected sepsis who received a CT within 72 hours of admission were given a final diagnosis of sepsis in 93.3% of cases (124/132). The detection of septic foci in 76.5% of CTs results in a high diagnostic yield for CT in septic ED patients, particularly in patients who are extremely ill and/or require ICU admission. Just et al [7] performed a single-center 1 year retrospective study of all CT scans of the chest, abdomen, or both ordered in pursuit of suspected infection in surgical ICU patients. A source of infection was found in 76/144 of cases (52.8%) and resulted in a change of management in 65/144 (45%) of patients, including a change in antimicrobial regimen, surgery, and nonsurgical interventions such as placement of drainage catheters. A pathologic infectious source was found in the chest in 72% of patients who underwent chest CT. Use of IV contrast was not specified in this study. Furthermore, preceding diagnostic procedures including chest radiography were not recorded. CT Chest Without and With IV Contrast There are no data to support the use of any added value of a CT chest without IV contrast immediately before acquisition of a contrast-enhanced CT in the diagnosis of sepsis.


Sepsis

Sepsis. FDG-PET/CT Skull Base to Mid-Thigh Tseng et al [9] performed a single-center retrospective observational study of 53 patients admitted with sepsis of unknown origin who underwent initial workup including unrevealing chest radiography followed by FDG-PET/CT within 2 weeks of sepsis diagnosis. Of these, 35/53 (66%) of patients had positive FDG-PET/CT findings and 13/53 (25%) of patients had treatment modified based on imaging results, which included surgery (9/13) and placement of drainage catheters (4/13). Although the majority of infections identified were musculoskeletal (19/53, 38%), the second most common site of infection was in the chest (13/53, 25%). Kluge et al [10] performed a single-center 6 year retrospective study of critically ill patients with severe sepsis or septic shock of unknown origin. Eighteen patients underwent initial workup, including unrevealing chest radiography followed by FDG-PET/CT (without any other prior cross-sectional imaging). Of these, 14/18 (78%) of patients had positive FDG-PET/CT findings, of which 3/18 (17%) of patients were false positives, 11/18 (61%) of patients were true positives, and 6/18 (33%) of patients had treatment modified based on imaging results, which included surgery and initiation/prolongation of antibiotic therapy. There were no false negatives (100% NPV). Brondserud et al [11] performed a single-center retrospective study of 157 patients with 165 separate episodes of bacteremia of unknown origin who had also undergone FDG-PET/CT as part of workup for infection or sepsis. FDG-PET/CT was able to detect the site of infection in 93/165 scans (56.4%). It was the first modality to identify the site of infection in 41.1% of cases, led to changes in antimicrobial therapy in 14.7% of patients, and resulted in a new infection-related diagnosis unrelated to bacteremia in 9.8% of episodes. FDG-PET/CT had a high clinical impact in 47.3% of cases and was independent of duration of preceding antimicrobial treatment as well as number of days of bacteremia.


Sepsis

Sepsis. Pijl et al [12] performed a single-center retrospective cohort study of all ICU patients with culture-proven blood stream infection over a 10 year period who had undergone FDG-PET/CT specifically to assess for source of Sepsis infection after an initial negative conventional workup. Of the 30 patients included in the study, FDG-PET/CT identified a source of infection in 70% of patients and had a sensitivity of 90.9% and a specificity of 87.5% with discharge diagnosis serving as the reference standard. The most common sources of infection found were pneumonia and septic arthritis. The overall PPV was 95.2%, and the NPV was 77.8% for identifying a focus of infection. Of the positive FDG-PET/CTs, 52% identified a new infectious focus that led to treatment modifications such as abscess drainage, removal of infected material, or change in antimicrobial therapy. FDG-PET/CT still resulted in treatment changes in an additional 14% who already had a known infectious focus. Given that PET/CT does not provide the same degree of anatomic localization as a dedicated diagnostic dose CT, PET/CT is not considered useful as the next imaging modality after chest radiograph. Therefore, it should only be considered for use after source localization with CT has failed. MRI Chest Without and With IV Contrast Although MRI can readily detect pulmonary and pleural infection, there are no data to support the use of MRI chest without and with IV contrast as the next diagnostic imaging study after normal, equivocal, or nonspecific chest radiography in the diagnosis of sepsis. MRI Chest Without IV Contrast Although MRI can readily detect pulmonary and pleural infection, there are no data to support the use of MRI chest without IV contrast as the next diagnostic imaging study after normal, equivocal, or nonspecific chest radiography in the diagnosis of sepsis. Variant 3: Suspected or confirmed sepsis. Acute abdominal pain. Initial imaging.


Sepsis

Sepsis. CT plays an important role in the evaluation of patients with suspected sepsis because of its high PPV [6] when performed as either an initial or follow-up imaging study, and which often leads to a change in management [7]. Septic foci are most commonly detected in the chest, abdomen, or pelvis. CT Abdomen and Pelvis With IV Contrast Pohlan et al [6] performed a retrospective study of 357 ED patients with suspected sepsis, of whom 132 underwent CT scan within 72 hours of admission. The second and third most commonly identified septic foci were in the abdomen, 22.0% (28/127 patients), and pelvis/genitourinary tract 20.5% (26/127 patients). A PPV of 81.82% (CI, 76.31%-86.28%) was calculated for septic foci identified by CT. However, the NPV was only 21.74% (CI, 10.73%- 39.11%). Patients with suspected sepsis who received a CT within 72 hours of admission were given a final diagnosis of sepsis in 93.3% of cases (124/132). The detection of septic foci in 76.5% of CTs results in a high diagnostic yield for CT in septic ED patients, particularly in patients who are extremely ill and/or require ICU admission. Just et al [7] performed a single-center 1 year retrospective study of all CT scans of the chest and/or abdomen ordered in pursuit of suspected infection in surgical ICU patients. A source of infection was found in 76/144 of cases (52.8%) and resulted in a change of management in 65/144 (45%) of patients, including a change in antimicrobial regimen, surgery, and nonsurgical interventions such as placement of drainage catheters. A pathologic infectious source was found in up to 44% of patients who underwent abdominal CT (exact breakdown not provided). Use of IV contrast was not specified in this study. Furthermore, preceding diagnostic procedures such as abdominal radiography were not recorded. Hoddick et al [13] performed a prospective study of 12 patients with urosepsis who were evaluated with both ultrasound (US) and CT.


Sepsis

Sepsis. Of these, 6/12 patients had renal abscesses, of whom 6/6 (100%) of the patients were identified on both US and contrast-enhanced CT. One patient had multiple perirenal abscesses, and another patient had a gas-forming perinephric abscess that were both missed by US but seen on CT. CT Abdomen and Pelvis Without and With IV Contrast There are no data to support the use of any added value of a CT abdomen and pelvis without IV contrast immediately before acquisition of a contrast-enhanced CT in the diagnosis of sepsis. Sepsis CT abdomen and pelvis with IV contrast but may be useful in specific clinical situations such as urosepsis from suspected obstructing renal calculi or ureteral calculi. FDG-PET/CT Skull Base to Mid-Thigh There are no data to support the use of FDG-PET/CT as an initial diagnostic imaging study in the diagnosis of sepsis. Fluoroscopy Contrast Enema There are no data to support the use of fluoroscopy contrast enema as an initial diagnostic imaging study in the diagnosis of sepsis. Fluoroscopy Upper GI Series with Small Bowel Follow-Through There are no data to support the use of fluoroscopy upper gastrointestinal (GI) series with small bowel follow- through as an initial diagnostic imaging study in the diagnosis of sepsis. MRI Abdomen and Pelvis Without and With IV Contrast There are no data to support the use of MRI abdomen and pelvis without and with IV contrast as an initial diagnostic imaging study in the diagnosis of sepsis. The majority of patients with sepsis are too unstable to undergo a relatively long imaging procedure, especially with the availability of alternate imaging modalities that are shorter and easier to obtain. However, in certain situations, such as targeting a specific source of clinically suspected infection, MRI has been shown to be useful. Given that perianal sepsis occurs in up to 10% of neutropenic patients, Ashkar et al [14] performed a retrospective review of neutropenic patients from hematologic malignancy who were given the diagnosis of perianal sepsis.


Sepsis

Sepsis. Of the 19 included patients, 9 patients underwent pelvic MRI without and with IV contrast. Of these, 88% (8/9) of the patients were found to have a focal collection compatible with a perianal abscess. This resulted in intraoperative drainage of the fluid collection in 6 patients, of whom 80% (5/6) of patients were confirmed to have a purulent draining cavity intraoperatively; 20% (1/6) of the patients was deemed to be a false-positive result. MRI Abdomen and Pelvis Without IV Contrast There are no data to support the use of MRI abdomen and pelvis without IV contrast as an initial diagnostic imaging study in the diagnosis of sepsis. Nuclear Medicine Scan Gallbladder There are no data to support the use of nuclear medicine scan gallbladder as an initial diagnostic imaging study in the diagnosis of sepsis. Radiography Abdomen Although abdominal radiography is portable and rapidly acquired, it rarely provides a definitive diagnosis in the setting of sepsis. It may provide information that increases the probability of an abdominal source such as pneumoperitoneum, but these findings would likely be suspected by physical examination and necessitate further evaluation with CT or US regardless [15,16]. US Abdomen Abdominal/pelvic US is often chosen as the initial imaging modality in patients of child-bearing age in the evaluation of suspected intraabdominal sepsis. Potential diagnoses responsible for sepsis in this setting can be divided into gynecological causes (such as endometritis, salpingitis, oophoritis, tubo-ovarian abscess, pelvic peritonitis) and nongynecological causes (such as acute appendicitis, diverticulitis, ileitis/colitis, epiploic appendagitis, and urological causes), which can be assessed to varying degrees on US [17]. In the setting of urosepsis, US is often considered the first imaging modality of choice in part because of its portability and rapid acquisition [15,16].


Sepsis

Sepsis. Based on recent studies, there is potential value in employment of artificial intelligence techniques to enhance the value of abdominal US in the setting of sepsis, but this discussion is beyond the scope of this topic. Sorenson et al [18] performed a retrospective review of 221 patients with first-time bacteremia suspected to be urosepsis. Of these, 116/221 (52%) of the patients underwent further evaluation with either abdominal US or abdomen/pelvis CT. Major abnormalities were found in 37/115 (32%) of patients and most commonly included pyonephrosis and renal calculi. Of these, 15/115 (13%) of the patients underwent urological intervention as a result of imaging findings. Follow-up of the 105 patients who did not undergo initial imaging revealed that 10/105 (9.5%) Sepsis of the patients were readmitted the following year with urosepsis; of these patients, imaging by US or CT was indicated for 6/10, and a major abnormality was detected in 3/6 imaged patients. Hoddick et al [13] performed a prospective study of 12 patients with urosepsis who were evaluated with both US and CT. Of these, 6/12 patients had renal abscesses, of whom 6/6 (100%) of the patients were identified on both US and contrast-enhanced CT. One patient had multiple perirenal abscesses, and another patient had a gas-forming perinephric abscess that were both missed by US but seen on CT. WBC Scan Abdomen and Pelvis There are no data to support the use of white blood cell (WBC) scan abdomen and pelvis as an initial diagnostic imaging study added in the diagnosis of sepsis. Variant 4: Suspected or confirmed sepsis. No specific symptoms suggestive of origin, or symptoms cannot be assessed. Initial imaging. CT plays an important role in the evaluation of patients with suspected sepsis because of its high PPV [6] when performed as either an initial or follow-up imaging study, which often leads to a change in management [7]. Septic foci are most commonly detected in the chest, abdomen, or pelvis.


Sepsis

Sepsis. Of note, transthoracic echocardiography, which plays an important role in the diagnosis of infective endocarditis and associated sepsis, is not addressed in this appropriateness criteria owing to the scope of the topic and that this imaging examination is typically performed outside of radiology. CT Abdomen and Pelvis With IV Contrast Pohlan et al [6] performed a retrospective study of 357 ED patients with suspected sepsis, of whom 132 underwent CT scan within 72 hours of admission. The second and third most commonly identified septic foci were in the abdomen, 22.0% (28/127 patients), and pelvis/genitourinary tract 20.5% (26/127 patients). A PPV of 81.82% (CI, 76.31%-86.28%) was calculated for septic foci identified by CT. However, the NPV was only 21.74% (CI, 10.73%- 39.11%). Patients with suspected sepsis who received a CT within 72 hours of admission were given a final diagnosis of sepsis in 93.3% of cases (124/132). The detection of septic foci in 76.5% of CTs results in a high diagnostic yield for CT in septic ED patients, particularly in patients who are extremely ill and/or require ICU admission. Just et al [7] performed a single-center 1 year retrospective study of all CT scans of the chest and/or abdomen ordered in pursuit of suspected infection in surgical ICU patients. A source of infection was found in 76/144 of cases (52.8%) and resulted in a change of management in 65/144 (45%) of patients, including a change in antimicrobial regimen, surgery, and nonsurgical interventions such as placement of drainage catheters. A pathologic infectious source was found in up to 44% of patients who underwent abdominal CT (exact breakdown not provided). Use of IV contrast was not specified in this study. Furthermore, preceding diagnostic procedures such as abdominal radiography were not recorded.


Sepsis

Sepsis. CT Abdomen and Pelvis Without and With IV Contrast There are no data to support the use of any added value of a CT abdomen and pelvis without IV contrast immediately before acquisition of a contrast-enhanced CT in the diagnosis of sepsis. CT Chest, Abdomen, and Pelvis With IV Contrast Pohlan et al [6] performed a retrospective study of 357 ED patients with suspected sepsis, of whom 132 underwent CT scan within 72 hours of admission. The most commonly identified source of infection, which the authors refer to as septic foci, was in the chest (pneumonia) reported in 38.6% (49/127) of patients. The second and third most commonly identified septic foci were in the abdomen, 22.0% (28/127 patients), and pelvis/genitourinary tract, 20.5% (26/127 patients). A PPV of 81.82% (CI, 76.31%-86.28%) was calculated for septic foci identified by CT. However, the NPV was only 21.74% (CI, 10.73%-39.11%). Patients with suspected sepsis who received a CT within 72 hours of admission were given a final diagnosis of sepsis in 93.3% of cases (124/132). The detection of Sepsis septic foci in 76.5% of CTs results in a high diagnostic yield for CT in septic ED patients, particularly in patients who are extremely ill and/or require ICU admission. Just et al [7] performed a single-center 1 year retrospective study of all CT scans of the chest, abdomen, or both ordered in pursuit of suspected infection in surgical ICU patients. A source of infection was found in 76/144 of cases (52.8%) and resulted in a change of management in 65/144 (45%) of patients, including a change in antimicrobial regimen, surgery, and nonsurgical interventions such as placement of drainage catheters. A pathologic infectious source was found in the chest in 72% of patients who underwent chest CT. A pathologic infectious source was found in up to 44% of patients who underwent abdominal CT (exact breakdown not provided). Use of IV contrast was not specified in this study. Furthermore, preceding diagnostic procedures including chest radiography were not recorded.


Sepsis

Sepsis. CT Chest, Abdomen, and Pelvis Without and With IV Contrast There are no data to support the use of any added value of a CT chest, abdomen, and pelvis without IV contrast immediately before acquisition of a contrast-enhanced CT in the diagnosis of sepsis. CT Chest With IV Contrast Pohlan et al [6] in a retrospective study of 357 ED patients with suspected sepsis, of whom 132 underwent CT scan within 72 hours of admission, the most commonly identified source of infection, which the authors refer to as septic foci, was in the chest (pneumonia) reported in 38.6% (49/127) of patients. A PPV of 81.82% (CI 76.31%-86.28%) was calculated for a septic focus identified by CT. However, the NPV was only 21.74% (CI 10.73%-39.11%). Patients with suspected sepsis who received a CT within 72 hours of admission were given a final diagnosis of sepsis in 93.3% of cases (124/132). The detection of septic foci in 76.5% of CTs results in a high diagnostic yield for CT in septic ED patients, particularly in patients who are extremely ill and/or require ICU admission. Just et al [7] performed a single-center 1 year retrospective study of all CT scans of the chest and/or abdomen ordered in pursuit of suspected infection in surgical ICU patients. A source of infection was found in 76/144 of cases (52.8%) and resulted in a change of management in 65/144 (45%) of patients, including a change in antimicrobial regimen, surgery, and nonsurgical interventions such as placement of drainage catheters. A pathologic infectious source was found in the chest in 72% of patients who underwent chest CT. Use of IV contrast was not specified in this study. Furthermore, preceding diagnostic procedures including chest radiography were not recorded. CT Chest Without and With IV Contrast There are no data to support the use of any added value of a CT chest without IV contrast immediately before acquisition of a contrast-enhanced CT in the diagnosis of sepsis.


Sepsis

Sepsis. FDG-PET/CT Skull Base to Mid-Thigh There are no data to support the use of FDG-PET/CT as an initial diagnostic imaging study in the diagnosis of sepsis. Fluoroscopy Contrast Enema There are no data to support the use of fluoroscopy contrast enema as an initial diagnostic imaging study in the diagnosis of sepsis. Sepsis Fluoroscopy Upper GI Series with Small Bowel Follow-Through There are no data to support the use of fluoroscopy upper GI series with small bowel follow-through as an initial diagnostic imaging study in the diagnosis of sepsis. MRI Abdomen and Pelvis Without and With IV Contrast There are no data to support the use of MRI abdomen and pelvis without and with IV contrast as an initial diagnostic imaging study in the diagnosis of sepsis. The majority of patients with sepsis are too unstable to undergo a relatively long imaging procedure, especially with the availability of alternate imaging modalities that are shorter and easier to obtain. However, in certain situations, such as targeting a specific source of clinically suspected infection, MRI has been shown to be useful. Given that perianal sepsis occurs in up to 10% of neutropenic patients, Ashkar et al [14] performed a retrospective review of neutropenic patients from hematologic malignancy who were given the diagnosis of perianal sepsis. Of the 19 included patients, 9 patients underwent pelvic MRI without and with IV contrast. Of these, 88% (8/9) of the patients were found to have a focal collection compatible with a perianal abscess. This resulted in intraoperative drainage of the fluid collection in 6 patients, of whom 80% (5/6) of patients were confirmed to have a purulent draining cavity intraoperatively; 20% (1/6) of the patients was deemed to be a false-positive result. MRI Abdomen and Pelvis Without IV Contrast There are no data to support the use of MRI abdomen and pelvis without IV contrast as an initial diagnostic imaging study in the diagnosis of sepsis.


Sepsis

Sepsis. MRI Chest Without and With IV Contrast Although MRI can readily detect pulmonary and pleural infection, there are no data to support the use of MRI chest without and with IV contrast as an initial diagnostic imaging study in the diagnosis of sepsis. MRI Chest Without IV Contrast Although MRI can readily detect pulmonary and pleural infection, there are no data to support the use of MRI chest without IV contrast as an initial diagnostic imaging study in the diagnosis of sepsis. Nuclear Medicine Scan Gallbladder There are no data to support the use of nuclear medicine scan gallbladder as an initial diagnostic imaging study in the diagnosis of sepsis. Radiography Abdomen Although abdominal radiography is portable and rapidly acquired (which is of obvious benefit for a suspected or confirmed septic patient), it rarely provides a definitive diagnosis in the setting of sepsis. It may provide information that increases the probability of an abdominal source such as pneumoperitoneum, but these findings would be suspected by physical examination and would still necessitate further evaluation with CT or US regardless [15,16]. Radiography Chest Chest radiography is a commonly obtained study in the ED because of its portability and rapid acquisition. Additionally, it has the potential of providing valuable information as an initial screening tool for pneumonia, particularly in patients with sepsis who may not be able to provide a history. Furthermore, chest radiography is commonly obtained in septic patients for the evaluation of adequate placement of external devices such as endotracheal tubes and central venous catheters at which time radiologists can concurrently evaluate for an underlying source of infection. Capp et al [8] performed a retrospective study of ED patients admitted to the ICU with the diagnosis of severe sepsis or septic shock over a 12 month period and evaluated the accuracy of chest radiography in the diagnosis of pneumonia.


Sepsis

Sepsis. Of 1,400 patients admitted to the ICU, 170 met criteria for severe sepsis or septic shock, and 85 were diagnosed with pneumonia. The sensitivity and specificity of initial chest radiography was 58% (95% CI, 46%- 68%) and 91% (95% CI, 81%-95%), respectively, for the diagnosis of pneumonia. US Abdomen Abdominal/pelvic US is often chosen as the initial imaging modality in patients of child-bearing age in the evaluation of suspected intraabdominal sepsis. Potential diagnoses responsible for sepsis in this setting can be divided into gynecological causes (such as endometritis, salpingitis, oophoritis, tubo-ovarian abscess, pelvic peritonitis) and nongynecological causes (such as acute appendicitis, diverticulitis, ileitis/colitis, epiploic appendagitis, and urological causes), which can be assessed to varying degrees on US [17]. In the setting of Sepsis urosepsis, US is often considered the first imaging modality of choice in part because of its portability and rapid acquisition (which is of obvious benefit for a suspected or confirmed septic patient) [15,16]. Based on recent studies, there is potential value in employment of artificial intelligence techniques to enhance the value of abdominal US in the setting of sepsis, but this discussion is beyond the scope of this topic. Sorenson et al [18] performed a retrospective review of 221 patients with first-time bacteremia suspected to be urosepsis. Of these, 116/221 (52%) of the patients underwent further evaluation with either abdominal US or abdomen/pelvis CT. Major abnormalities were found in 37/115 (32%) of the patients and most commonly included pyonephrosis and renal calculi. Of these, 15/115 (13%) of the patients underwent urological intervention as a result of imaging findings.


Sepsis

Sepsis. Follow-up of the 105 patients who did not undergo initial imaging revealed that 10/105 (9.5%) of the patients were readmitted the following year with urosepsis; of these patients, imaging by US or CT was indicated for 6/10, and a major abnormality was detected in 3/6 imaged patients. Hoddick et al [13] performed a prospective study of 12 patients with urosepsis who were evaluated with both US and CT. Of these, 6/12 patients had renal abscesses, of whom 6/6 (100%) of the patients were identified on both US and contrast-enhanced CT. One patient had multiple perirenal abscesses, and another patient had a gas-forming perinephric abscess that were both missed by US but seen on CT. WBC Scan Abdomen and Pelvis There are no data to support the use of WBC scan abdomen and pelvis as an initial diagnostic imaging study in the diagnosis of sepsis. Variant 5: Suspected or confirmed sepsis. No specific symptoms suggestive of origin, or symptoms cannot be assessed. Normal or equivocal or nonspecific chest radiograph. Next imaging study. CT plays an important role in the evaluation of patients with suspected sepsis because of its high PPV [6] when performed as either an initial or follow-up imaging study, which often leads to a change in management [7]. Septic foci are most commonly detected in the chest, abdomen, or pelvis. Of note, transthoracic echocardiography, which plays an important role in the diagnosis of infective endocarditis and associated sepsis, is not addressed in this appropriateness criteria owing to the scope of the topic and that this imaging examination is typically performed outside of radiology. CT Abdomen and Pelvis With IV Contrast Pohlan et al [6] in a retrospective study of 357 ED patients with suspected sepsis, of whom 132 underwent CT scan within 72 hours of admission, the second and third most commonly identified septic foci were in the abdomen, 22.0% (28/127 patients), and pelvis/genitourinary tract, 20.5% (26/127 patients).


Sepsis

Sepsis. A PPV of 81.82% (CI 76.31%- 86.28%) was calculated for a septic focus identified by CT. However, the NPV was only 21.74% (CI 10.73%- 39.11%). Patients with suspected sepsis who received a CT within 72 hours of admission were given a final diagnosis of sepsis in 93.3% of cases. The detection of septic foci in 76.5% of CTs results in a high diagnostic yield for CT in septic ED patients, particularly in patients who are extremely ill and/or require ICU admission. Just et al [7] performed a single-center 1 year retrospective study of all CT scans of the chest, abdomen, or both ordered in pursuit of suspected infection in surgical ICU patients. A source of infection was found in 76/144 of cases (52.8%) and resulted in a change of management in 65/144 (45%) of patients, including a change in antimicrobial regimen, surgery, and nonsurgical interventions such as placement of drainage catheters. A pathologic infectious source was found in up to 44% of patients who underwent abdominal CT (exact breakdown not provided). Use of IV contrast was not specified in this study. Furthermore, preceding diagnostic procedures including chest radiography were not recorded. Hoddick et al [13] performed a prospective study of 12 patients with urosepsis who were evaluated with both US and CT. Of these, 6/12 patients had renal abscesses, of whom 6/6 (100%) of patients were identified on both US and contrast-enhanced CT. One patient had multiple perirenal abscesses, and another patient had a gas-forming perinephric abscess that were both missed by US but seen on CT. CT Abdomen and Pelvis Without and With IV Contrast There are no data to support the use of any added value of a CT abdomen and pelvis without IV contrast immediately before acquisition of a contrast-enhanced CT in the diagnosis of sepsis. Sepsis CT Chest, Abdomen, and Pelvis With IV Contrast Pohlan et al [6] performed a retrospective study of 357 ED patients with suspected sepsis, of whom 132 underwent CT scan within 72 hours of admission.


Sepsis

Sepsis. The most commonly identified source of infection, which the authors refer to as septic foci, was in the chest (pneumonia) reported in 38.6% (49/127) of patients. The second and third most commonly identified septic foci were in the abdomen, 22.0% (28/127 patients), and pelvis/genitourinary tract, 20.5% (26/127 patients). A PPV of 81.82% (CI, 76.31%-86.28%) was calculated for septic foci identified by CT. However, the NPV was only 21.74% (CI, 10.73%-39.11%). Patients with suspected sepsis who received a CT within 72 hours of admission were given a final diagnosis of sepsis in 93.3% of cases (124/132). The detection of septic foci in 76.5% of CTs results in a high diagnostic yield for CT in septic ED patients, particularly in patients who are extremely ill and/or require ICU admission. Just et al [7] performed a single-center 1 year retrospective study of all CT scans of the chest, abdomen, or both ordered in pursuit of suspected infection in surgical ICU patients. A source of infection was found in 76/144 of cases (52.8%) and resulted in a change of management in 65/144 (45%) of patients, including a change in antimicrobial regimen, surgery, and nonsurgical interventions such as placement of drainage catheters. A pathologic infectious source was found in the chest in 72% of patients who underwent chest CT. A pathologic infectious source was found in up to 44% of patients who underwent abdominal CT (exact breakdown not provided). Use of IV contrast was not specified in this study. Furthermore, preceding diagnostic procedures including chest radiography were not recorded. CT Chest, Abdomen, and Pelvis Without and With IV Contrast There are no data to support the use of any added value of a CT chest, abdomen, and pelvis without IV contrast immediately before acquisition of a contrast-enhanced CT in the diagnosis of sepsis.


Sepsis

Sepsis. CT Chest With IV Contrast Pohlan et al [6] in a retrospective study of 357 ED patients with suspected sepsis, of whom 132 underwent CT scan within 72 hours of admission, the most commonly identified source of infection, which the authors refer to as septic foci, was in the chest (pneumonia) reported in 38.6% (49/127) of patients. A PPV of 81.82% (CI 76.31%-86.28%) was calculated for a septic focus identified by CT. However, the NPV was only 21.74% (CI 10.73%-39.11%). Patients with suspected sepsis who received a CT within 72 hours of admission were given a final diagnosis of sepsis in 93.3% of cases (124/132). The detection of septic foci in 76.5% of CTs results in a high diagnostic yield for CT in septic ED patients, particularly in patients who are extremely ill and/or require ICU admission. Just et al [7] performed a single-center 1 year retrospective study of all CT scans of the chest, abdomen, or both ordered in pursuit of suspected infection in surgical ICU patients. A source of infection was found in 76/144 of cases (52.8%) and resulted in a change of management in 65/144 (45%) of patients, including a change in antimicrobial regimen, surgery, and nonsurgical interventions such as placement of drainage catheters. A pathologic infectious source was found in the chest in 72% of patients who underwent chest CT. Use of IV contrast was not specified in this study. Furthermore, preceding diagnostic procedures including chest radiography were not recorded. Sepsis CT Chest Without and With IV Contrast There are no data to support the use of any added value of a CT chest without IV contrast immediately before acquisition of a contrast-enhanced CT in the diagnosis of sepsis. FDG-PET/CT Skull Base to Mid-Thigh Tseng et al [9] performed a single-center retrospective observational study of 53 patients admitted with sepsis of unknown origin who underwent initial workup including unrevealing chest radiography followed by FDG-PET/CT within 2 weeks of sepsis diagnosis.