Imaging after Pancreatic Surgery: Expected Findings and Postoperative Complications.

Pancreatic surgery is considered one of the most technically challenging surgical procedures, despite the evolution of modern techniques. Neoplasms remain the most common indication for pancreatic surgery, although inflammatory conditions may also prompt surgical evaluation. The choice of surgical procedure depends on the type and location of the pathologic finding because different parts of the pancreas have separate vascular supplies that may be shared by adjacent organs. The surgical approach could be conventional or minimally invasive (laparoscopic, endoscopic, or robotic assisted). Because of the anatomic complexity of the pancreatic bed, perioperative complications may be frequently encountered and commonly involve the pancreatic-biliary, vascular, lymphatic, or bowel systems, irrespective of the surgical technique used. Imaging plays an important role in the assessment of suspected postoperative complications, with CT considered the primary imaging modality, while MRI, digital subtraction angiography, and molecular imaging are considered ancillary diagnostic tools. Accurate diagnosis of postoperative complications requires a solid understanding of pancreatic anatomy, surgical indications, normal postoperative appearance, and expected postsurgical changes. The practicing radiologist should be familiar with the most common perioperative complications, such as anastomotic leak, abscess, and hemorrhage, and be able to differentiate these entities from normal anticipated postoperative changes such as seroma, edema and fat stranding at the surgical site, and perivascular soft-tissue thickening. In addition to evaluation of the primary operative fossa, imaging plays a fundamental role in assessment of the adjacent organ systems secondarily affected after pancreatic surgery, such as vascular, biliary, and enteric complications. Published under a CC BY 4.0 license. Test Your Knowledge questions are available in the supplemental material. See the invited commentary by Winslow in this issue.

ACR Appropriateness Criteria® Left Lower Quadrant Pain: 2023 Update.

The differential diagnosis for left lower quadrant pain is wide and conditions range from the benign and self-limited to life-threatening surgical emergencies. Along with patient history, physical examination, and laboratory tests, imaging is often critical to limit the differential diagnosis and identify life-threatening abnormalities. This document will discuss the guidelines for the appropriate use of imaging in the initial workup for patients who present with left lower quadrant pain, patients with suspected diverticulitis, and patients with suspected complications from diverticulitis. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation.

MRI assessment of rectal cancer response to neoadjuvant therapy: a multireader study.

OBJECTIVES: A watch and wait strategy with the goal of organ preservation is an emerging treatment paradigm for rectal cancer following neoadjuvant treatment. However, the selection of appropriate patients remains a challenge. Most previous efforts to measure the accuracy of MRI in assessing rectal cancer response used a small number of radiologists and did not report variability among them. METHODS: Twelve radiologists from 8 institutions assessed baseline and restaging MRI scans of 39 patients. The participating radiologists were asked to assess MRI features and to categorize the overall response as complete or incomplete. The reference standard was pathological complete response or a sustained clinical response for > 2 years. RESULTS: We measured the accuracy and described the interobserver variability of interpretation of rectal cancer response between radiologists at different medical centers. Overall accuracy was 64%, with a sensitivity of 65% for detecting complete response and specificity of 63% for detecting residual tumor. Interpretation of the overall response was more accurate than the interpretation of any individual feature. Variability of interpretation was dependent on the patient and imaging feature investigated. In general, variability and accuracy were inversely correlated. CONCLUSIONS: MRI-based evaluation of response at restaging is insufficiently accurate and has substantial variability of interpretation. Although some patients' response to neoadjuvant treatment on MRI may be easily recognizable, as seen by high accuracy and low variability, that is not the case for most patients. KEY POINTS: • The overall accuracy of MRI-based response assessment is low and radiologists differed in their interpretation of key imaging features. • Some patients' scans were interpreted with high accuracy and low variability, suggesting that these patients' pattern of response is easier to interpret. • The most accurate assessments were those of the overall response, which took into consideration both T2W and DWI sequences and the assessment of both the primary tumor and the lymph nodes.

Targeted degradation via direct 26S proteasome recruitment.

Engineered destruction of target proteins by recruitment to the cell's degradation machinery has emerged as a promising strategy in drug discovery. The majority of molecules that facilitate targeted degradation do so via a select number of ubiquitin ligases, restricting this therapeutic approach to tissue types that express the requisite ligase. Here, we describe a new strategy of targeted protein degradation through direct substrate recruitment to the 26S proteasome. The proteolytic complex is essential and abundantly expressed in all cells; however, proteasomal ligands remain scarce. We identify potent peptidic macrocycles that bind directly to the 26S proteasome subunit PSMD2, with a 2.5-Å-resolution cryo-electron microscopy complex structure revealing a binding site near the 26S pore. Conjugation of this macrocycle to a potent BRD4 ligand enabled generation of chimeric molecules that effectively degrade BRD4 in cells, thus demonstrating that degradation via direct proteasomal recruitment is a viable strategy for targeted protein degradation.

ACR Appropriateness Criteria® Hernia.

Abdominopelvic hernias are common clinical entities composed of a wide variety of congenital, traumatic, and iatrogenic etiologies. Any weakness in the body wall may result in hernia of cavity contents with concomitant risks of morbidity and mortality. Presentations may be specific, palpable body wall mass/bulge, or vague, nonspecific pain through bowel obstruction. This document focuses on initial imaging of the adult population with signs of symptoms prompting suspicion of abdominopelvic hernia. Imaging of the abdomen and pelvis to evaluate defects is essential for prompt diagnosis and treatment. Often CT and ultrasound are the first-line modalities to quickly evaluate the abdomen and pelvis, providing for accurate diagnoses and management of patients. MRI protocols may be useful as first-line imaging studies, especially in patients with orthopedic instrumentation. Although often performed, abdominal radiographs and fluorographic procedures may provide indirect evidence of hernias but are usually not indicated for initial diagnosis of hernia. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer-reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances in which peer-reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation.

ACR Appropriateness Criteria® Right Lower Quadrant Pain: 2022 Update.

This document focuses on imaging in the adult and pregnant populations with right lower quadrant (RLQ) abdominal pain, including patients with fever and leukocytosis. Appendicitis remains the most common surgical pathology responsible for RLQ abdominal pain in the United States. Other causes of RLQ pain include right colonic diverticulitis, ureteral stone, and infectious enterocolitis. Appropriate imaging in the diagnosis of appendicitis has resulted in decreased negative appendectomy rate from as high as 25% to approximately 1% to 3%. Contrast-enhanced CT remains the primary and most appropriate imaging modality to evaluate this patient population. MRI is approaching CT in sensitivity and specificity as this technology becomes more widely available and utilization increases. Unenhanced MRI and ultrasound remain the diagnostic procedures of choice in the pregnant patient. MRI and ultrasound continue to perform best in the hands of the experts. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer-reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances in which peer-reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation.

Review of uterine fibroids: imaging of typical and atypical features, variants, and mimics with emphasis on workup and FIGO classification.

Uterine fibroids are the most common gynecologic neoplasm. Although non-degenerated fibroids are easily identifiable on imaging, degenerated fibroids, fibroid variants, and fibroids with unusual growth patterns can constitute a diagnostic dilemma. Identification of these abnormal morphologic features can alter the diagnosis of presumed uterine fibroids and hence change management plans. This article reviews the typical and atypical radiologic imaging features of uterine fibroids, with an emphasis on the pitfalls, mimics, and radiologically identifiable features that can alter clinical management plans.

ACR Appropriateness Criteria® Staging of Colorectal Cancer: 2021 Update.

Preoperative imaging of rectal carcinoma involves accurate assessment of the primary tumor as well as distant metastatic disease. Preoperative imaging of nonrectal colon cancer is most beneficial in identifying distant metastases, regardless of primary T or N stage. Surgical treatment remains the definitive treatment for colon cancer, while organ-sparing approach may be considered in some rectal cancer patients based on imaging obtained before and after neoadjuvant treatment. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

ACR Appropriateness Criteria® Anorectal Disease.

This review summarizes the relevant literature for the selection of the initial imaging in 4 clinical scenarios in patients with suspected inflammatory disease or postoperative complication of the anorectum. These clinical scenarios include suspected perianal fistula or abscess; rectovesicular or rectovaginal fistula; proctitis or pouchitis; and suspected complication following proctectomy, coloproctectomy, or colectomy with a pouch or other anastomosis. The appropriateness of imaging modalities as they apply to each clinical scenario is rated as usually appropriate, may be appropriate, and usually not appropriate to assist the selection of the most appropriate imaging modality in the corresponding clinical scenarios of anorectal disease. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

Can Hernia Sac to Abdominal Cavity Volume Ratio Predict Fascial Closure Rate for Large Ventral Hernia? Reliability of the Tanaka Score.

BACKGROUND: The hernia sac to abdominal cavity volume ratio (VR) on abdominal CT was described previously as a way to predict which hernias would be less likely to achieve fascial closure. The aim of this study was to test the reliability of the previously described cutoff ratio in predicting fascial closure in a cohort of patients with large ventral hernias. METHODS: Patients who underwent elective, open incisional hernia repair of 18 cm or larger width at a single center were identified. The primary end point of interest was fascial closure for all patients. Secondary outcomes included operative details and abdominal wall-specific quality-of-life metrics. We used VR as a comparison variable and calculated the test characteristics (ie, sensitivity, specificity, and positive and negative predictive values). RESULTS: A total of 438 patients were included, of which 337 (77%) had complete fascial closure and 101 (23%) had incomplete fascial closure. The VR cutoff of 25% had a sensitivity of 76% (95% CI, 71% to 80%), specificity of 64% (95% CI, 54% to 74%), positive predictive value of 88% (95% CI, 83% to 91%), and negative predictive value of 45% (95% CI, 36% to 53%). The incomplete fascial closure group had significantly lower quality of life scores at 1 year (83.3 vs 52.5; p = 0.001), 2 years (85 vs 33.3; p = 0.003), and 3 years (86.7 vs 63.3; p = 0.049). CONCLUSIONS: In our study, the VR cutoff of 25% was sensitive for predicting complete fascial closure for patients with ratios below this threshold. Although there is a higher likelihood of incomplete fascial closure when VR is ≥ 25%, this end point cannot be predicted reliably. Additional studies should be done to study this ratio in conjunction with other hernia-related variables to better predict this important surgical end point.

Activation of the IRE1 RNase through remodeling of the kinase front pocket by ATP-competitive ligands.

Inositol-Requiring Enzyme 1 (IRE1) is an essential component of the Unfolded Protein Response. IRE1 spans the endoplasmic reticulum membrane, comprising a sensory lumenal domain, and tandem kinase and endoribonuclease (RNase) cytoplasmic domains. Excess unfolded proteins in the ER lumen induce dimerization and oligomerization of IRE1, triggering kinase trans-autophosphorylation and RNase activation. Known ATP-competitive small-molecule IRE1 kinase inhibitors either allosterically disrupt or stabilize the active dimeric unit, accordingly inhibiting or stimulating RNase activity. Previous allosteric RNase activators display poor selectivity and/or weak cellular activity. In this study, we describe a class of ATP-competitive RNase activators possessing high selectivity and strong cellular activity. This class of activators binds IRE1 in the kinase front pocket, leading to a distinct conformation of the activation loop. Our findings reveal exquisitely precise interdomain regulation within IRE1, advancing the mechanistic understanding of this important enzyme and its investigation as a potential small-molecule therapeutic target.

ACR Appropriateness Criteria® Suspected Small-Bowel Obstruction.

Small-bowel obstruction is a common cause of abdominal pain and accounts for a significant proportion of hospital admissions. Radiologic imaging plays the key role in the diagnosis and management of small-bowel obstruction as neither patient presentation, the clinical examination, nor laboratory testing are sufficiently sensitive or specific enough to diagnose or guide management. This document focuses on the imaging evaluation of the two most commonly encountered clinical scenarios related to small-bowel obstruction: the acute presentation and the more indolent, low-grade, or intermittent presentation. This document hopes to clarify the appropriate utilization of the many imaging procedures that are available and commonly employed in these clinical settings. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

ACR Appropriateness Criteria® Crohn Disease.

Three common clinical scenarios involving use of imaging in Crohn disease are covered. These include the initial evaluation of Crohn disease when the diagnosis has not been previously established, the evaluation for anticipated exacerbation of known disease, and the evaluation of disease activity during therapy monitoring. The appropriateness of a given imaging modality for each scenario is rated as one of three categories (usually appropriate, may be appropriate, usually not appropriate) to help guide evaluation. Pediatric presentation of Crohn disease and the appropriateness of imaging are not covered in this document. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

Cyanopyrrolidine Inhibitors of Ubiquitin Specific Protease 7 Mediate Desulfhydration of the Active-Site Cysteine.

Ubiquitin specific protease 7 (USP7) regulates the protein stability of key cellular regulators in pathways ranging from apoptosis to neuronal development, making it a promising therapeutic target. Here we used an engineered, activated variant of the USP7 catalytic domain to perform structure-activity studies of electrophilic peptidomimetic inhibitors. Employing this USP7 variant, we found that inhibitors with a cyanopyrrolidine warhead unexpectedly promoted a ß-elimination reaction of the initial covalent adducts, thereby converting the active-site cysteine residue to dehydroalanine. We determined that this phenomenon is specific for the USP7 catalytic cysteine and that structural features of the inhibitor and protein microenvironment impact elimination rates. Using comprehensive docking studies, we propose that the characteristic conformational dynamics of USP7 allow access to conformations that promote the ligand-induced elimination. Unlike in conventional reversible-covalent inhibition, the compounds described here irreversibly destroy a catalytic residue while simultaneously converting the inhibitor to a nonelectrophilic byproduct. Accordingly, this unexpected finding expands the scope of covalent inhibitor modalities and offers intriguing insights into enzyme-inhibitor dynamics.

Small bowel transplant: state-of-the-art vascular and nonvascular imaging.

BACKGROUND: Small bowel transplant (SBT) is a surgical procedure that may be used in patients with pathology resulting in severe intestinal failure resistant to conventional forms of surgical and nonsurgical treatment. Intestinal failure is defined as the failure of enterocytes to absorb sufficient macronutrients, water, and/or electrolytes to sustain homeostasis and/or promote growth. With the advancement of surgical techniques and advancements in perioperative transplant management, SBT has become an increasingly common treatment for intestinal failure, with survival rates for SBT comparable to those for other solid organ transplants. MATERIALS AND METHODS: This review provides background on SBT, its variations, and the associated preoperative and postoperative imaging studies with regard to surgical planning and anticipated complications. RESULTS AND CONCLUSIONS: With the increasing use of SBT, radiologists will be expected to be familiar with the diagnostic studies and available endovascular interventions associated with this procedure.

Endothelial intercellular cell adhesion molecule 1 contributes to cell aggregate formation in CHO cells cultured in serum-free media.

Chinese hamster ovary (CHO) cells have been adapted to grow in serum-free media and in suspension culture to facilitate manufacturing needs. Some CHO cell lines, however, tend to form cell aggregates while being cultured in suspension. This can result in reduced viability and capacity for single cell cloning (SCC) via limiting dilution, and process steps to mitigate cell aggregate formation, for example, addition of anti-cell-aggregation agents. In this study, we have identified endothelial intercellular cell adhesion molecule 1 (ICAM-1) as a key protein promoting cell aggregate formation in a production competent CHO cell line, which is prone to cell aggregate formation. Knocking out (KO) the ICAM-1 gene significantly decreased cell aggregate formation in the culture media without anti-cell-aggregation reagent. This trait can simplify the process of transfection, selection, automated clone isolation, and so on. Evaluation in standard cell line development of ICAM-1 KO and wild-type CHO hosts did not reveal any noticeable impacts on titer or product quality. Furthermore, analysis of a derived nonaggregating cell line showed significant reductions in expression of cell adhesion proteins. Overall, our data suggest that deletion of ICAM-1 and perhaps other cell adhesion proteins can reduce cell aggregate formation and improve clonality assurance during SCC.

ACR Appropriateness Criteria® Palpable Abdominal Mass-Suspected Neoplasm.

Palpable abdominal masses may arise from the abdominal cavity or the abdominal wall. The differential diagnosis is broad for each variant ranging from benign lipomas, inflammatory processes, to malignant tumors. The imaging approach to diagnosis varies by location. For intra-abdominal masses, contrast-enhanced CT and ultrasound examination have demonstrated accuracy. For abdominal wall masses, which may arise from muscle, subcutaneous tissue, or connective tissue, MRI, CT, and ultrasound all provide diagnostic value. This publication reviews the current evidence supporting the imaging approach to diagnosis of palpable abdominal masses for two variants: suspected intra-abdominal neoplasm and suspected abdominal wall masses. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

ACR Appropriateness Criteria® Left Lower Quadrant Pain-Suspected Diverticulitis.

This review summarizes the relevant literature regarding imaging of suspected diverticulitis as an etiology for left lower quadrant pain, and imaging of complications of acute diverticulitis. The most common cause of left lower quadrant pain in adults is acute sigmoid or descending colonic diverticulitis. Appropriate imaging triage for patients with suspected diverticulitis should address the differential diagnostic possibilities and what information is necessary to make a definitive management decision. Patients with diverticulitis may require surgery or interventional radiology procedures because of associated complications, including abscesses, fistulas, obstruction, or perforation. As a result, there has been a trend toward greater use of imaging to confirm the diagnosis of diverticulitis, evaluate the extent of disease, and detect complications before deciding on appropriate treatment. Additionally, in the era of bundled payments and minimizing health care costs, patients with acute diverticulitis are being managed on an outpatient basis and rapid diagnostic imaging at the time of initial symptoms helps to streamline and triage patients to the appropriate treatment pathway. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

Hepatic capsular retraction: An updated MR imaging review.

Hepatic capsular retraction is a morphologic descriptor that refers to invagination or focal flattening of the typical smooth contour of the liver capsule. It is an uncommon finding that, when combined with other imaging features and clinical context, can help to refine the differential diagnosis in patients with liver lesions. Although this descriptor has historically been used in reference to a small subset of benign and malignant lesions, the differential has since been expanded with the discovery of new entities causing capsular retraction as well as with novel and increased use of liver-directed treatment techniques. Additionally, modern imaging techniques now allow for improved detection and characterization of capsular retraction. In this review, we discuss these common and uncommon causes of capsular retraction, with an emphasis on findings from body MRI.