Histological improvements following energy restriction and exercise: The role of insulin resistance in resolution of MASH.

BACKGROUND & AIMS: Metabolic dysfunction-associated steatohepatitis (MASH) is one of the most common liver diseases worldwide and is characterized by multi-tissue insulin resistance. The effects of a 10-month energy restriction and exercise intervention on liver histology, anthropometrics, plasma biochemistries, and insulin sensitivity were compared to standard of care (control) to understand mechanisms that support liver health improvements. METHODS: Following medical diagnosis of MASH, individuals were randomized to treatment (n = 16) or control (n = 8). Liver fat (magnetic resonance spectroscopy), 18-hour plasma biochemical measurements, and isotopically labeled hyperinsulinemic-euglycemic clamps were completed pre- and post-intervention. Body composition and cardiorespiratory fitness (VO2peak) were also measured mid-intervention. Those in the treatment group were counseled to reduce energy intake and completed supervised, high-intensity interval training (3x/week) for 10 months. Controls continued physician-directed care. RESULTS: Treatment induced significant (p <0.05) reductions in body weight, fat mass, and liver injury, while VO2peak (p <0.05) and non-esterified fatty acid suppression (p = 0.06) were improved. Both groups exhibited reductions in total energy intake, hemoglobin A1c, hepatic insulin resistance, and liver fat (p <0.05). Compared to control, treatment induced a two-fold increase in peripheral insulin sensitivity which was significantly related to higher VO2peak and resolution of liver disease. CONCLUSIONS: Exercise and energy restriction elicited significant and clinically meaningful treatment effects on liver health, potentially driven by a redistribution of excess nutrients to skeletal muscle, thereby reducing hepatic nutrient toxicity. Clinical guidelines should emphasize the addition of aerobic exercise in lifestyle treatments for the greatest histologic benefit in individuals with advanced MASH. IMPACT AND IMPLICATIONS: The mechanisms that underpin histologic improvement in individuals with metabolic dysfunction-associated steatohepatitis (MASH) are not well understood. This study evaluated the relationship between liver and metabolic health, testing how changes in one may affect the other. We investigated the effects of energy restriction and exercise on the association between multi-tissue insulin sensitivity and histologic improvements in participants with biopsy-proven MASH. For the first time, these results show that an improvement in peripheral (but not hepatic) insulin sensitivity and systemic markers of muscle function (i.e. cardiorespiratory fitness) were strongly related to resolution of liver disease. Extrahepatic disposal of substrates and improved fitness levels supported histologic improvement, confirming the addition of exercise as crucial to lifestyle interventions in MASH. CLINICAL TRIAL NUMBER: NCT03151798.

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.

The Peritoneum: Anatomy, Pathologic Findings, and Patterns of Disease Spread.

Disease spread in the abdomen and pelvis generally occurs in a predictable pattern in relation to anatomic landmarks and fascial planes. Anatomically, the abdominopelvic cavity is subdivided into several smaller spaces or compartments by key ligaments and fascial planes. The abdominal cavity has been traditionally divided into peritoneal, retroperitoneal, and pelvic extraperitoneal spaces. Recently, more clinically relevant classifications have evolved. Many pathologic conditions affect the abdominal cavity, including traumatic, inflammatory, infectious, and neoplastic processes. These abnormalities can extend beyond their sites of origin through various pathways. Identifying the origin of a disease process is the first step in formulating a differential diagnosis and ultimately reaching a final diagnosis. Pathologic conditions differ in terms of pathways of disease spread. For example, simple fluid tracks along fascial planes, respecting anatomic boundaries, while fluid from acute necrotizing pancreatitis can destroy fascial planes, resulting in transfascial spread without regard for anatomic landmarks. Furthermore, neoplastic processes can spread through multiple pathways, with a propensity for spread to noncontiguous sites. When the origin of a disease process is not readily apparent, recognizing the spread pattern can allow the radiologist to work backward and ultimately arrive at the site or source of pathogenesis. As such, a cohesive understanding of the peritoneal anatomy, the typical organ or site of origin for a disease process, and the corresponding pattern of disease spread is critical not only for initial diagnosis but also for establishing a road map for staging, anticipating further disease spread, guiding search patterns and report checklists, determining prognosis, and tailoring appropriate follow-up imaging studies. ©RSNA, 2024 Supplemental material is available for this article.

Paraneoplastic Syndromes from Head to Toe: Pathophysiology, Imaging Features, and Workup.

Patients often have symptoms due to the mass effect of a neoplasm on surrounding tissues or the development of distant metastases. However, some patients may present with clinical symptoms that are not attributable to direct tumor invasion. In particular, certain tumors may release substances such as hormones or cytokines or trigger an immune cross-reactivity between malignant and normal body cells, resulting in characteristic clinical features that are broadly referred to as paraneoplastic syndromes (PNSs). Recent advances in medicine have improved the understanding of the pathogenesis of PNSs and enhanced their diagnosis and treatment. It is estimated that 8% of patients with cancer develop a PNS. Diverse organ systems may be involved, most notably the neurologic, musculoskeletal, endocrinologic, dermatologic, gastrointestinal, and cardiovascular systems. Knowledge of various PNSs is necessary, as these syndromes may precede tumor development, complicate the patient's clinical presentation, indicate tumor prognosis, or be mistaken for metastatic spread. Radiologists should be familiar with the clinical presentations of common PNSs and the selection of appropriate imaging examinations. Many of these PNSs have imaging features that can assist with arriving at the correct diagnosis. Therefore, the key radiographic findings associated with these PNSs and the diagnostic pitfalls that can be encountered during imaging are important, as their detection can facilitate early identification of the underlying tumor, reveal early recurrence, and enable monitoring of the patient's response to therapy. © RSNA, 2023 Quiz questions for this article are available in the supplemental material.

Fatty Acid Synthase Inhibitor TVB-2640 Reduces Hepatic de Novo Lipogenesis in Males With Metabolic Abnormalities.

BACKGROUND AND AIMS: Elevated hepatic de novo lipogenesis (DNL) is a key distinguishing characteristic of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis. In rodent models of NAFLD, treatment with a surrogate of TVB-2640, a pharmacological fatty acid synthase inhibitor, has been shown to reduce hepatic fat and other biomarkers of DNL. The purpose of this phase I clinical study was to test the effect of the TVB-2640 in obese men with certain metabolic abnormalities that put them at risk for NAFLD. APPROACH AND RESULTS: Twelve subjects (mean ± SEM, 42 ± 2 years, body mass index 37.4 ± 1.2 kg/m2 , glucose 103 ± 2 mg/dL, triacylglycerols 196 ± 27 mg/dL, and elevated liver enzymes) underwent 10 days of treatment with TVB-2640 at doses ranging from 50-150 mg/day. Food intake was controlled throughout the study. Hepatic DNL was measured before and after an oral fructose/glucose bolus using isotopic labeling with 1-13 C1 -acetate intravenous infusion, followed by measurement of labeled very low-density lipoprotein palmitate via gas chromatography mass spectometry. Substrate oxidation was measured by indirect calorimetry. Across the range of doses, fasting DNL was reduced by up to 90% (P = 0.003). Increasing plasma concentrations of TVB-2640 were associated with progressive reductions in the percent of fructose-stimulated peak fractional DNL (R2  = -0.749, P = 0.0003) and absolute DNL area under the curve 6 hours following fructose/glucose bolus (R2  = -0.554, P = 0.005). For all subjects combined, alanine aminotransferase was reduced by 15.8 ± 8.4% (P = 0.05). Substrate oxidation was unchanged, and safety monitoring revealed that the drug was well tolerated, without an increase in plasma triglycerides. Alopecia occurred in 2 subjects (reversed after stopping the drug), but otherwise no changes were observed in fasting glucose, insulin, ketones, and renal function. CONCLUSION: These data support the therapeutic potential of a fatty acid synthase inhibitor, TVB-2640 in particular, in patients with NAFLD and nonalcoholic steatohepatitis.

Ligament of Treitz: Anatomy, Relevance of Radiologic Findings, and Radiologic-Pathologic Correlation.

OBJECTIVE. The objective of this article is to discuss the anatomy, embryonic origin, normal variants, and various attachments of the ligament of Treitz. We also describe the pathologic processes that develop along the ligament of Treitz and the role of cross-sectional imaging in identifying these conditions. CONCLUSION. The ligament of Treitz, also known as the suspensory ligament of the duodenum, is an important anatomic landmark in the abdomen. It is essential that radiologists understand the anatomic attachments, normal variants, and various pathologic conditions involving the ligament of Treitz as well as the role of cross-sectional imaging in the assessment of these conditions.

Clinical Importance of Incidental Homogeneous Renal Masses That Measure 10-40 mm and 21-39 HU at Portal Venous Phase CT: A 12-Institution Retrospective Cohort Study.

BACKGROUND. Incidental homogeneous renal masses are frequently encountered at portal venous phase CT. The American College of Radiology Incidental Findings Committee's white paper on renal masses recommends additional imaging for incidental homogeneous renal masses greater than 20 HU, but single-center data and the Bosniak classification version 2019 suggest the optimal attenuation threshold for detecting solid masses should be higher. OBJECTIVE. The purpose of this article is to determine the clinical importance of small (10-40 mm) incidentally detected homogeneous renal masses measuring 21-39 HU at portal venous phase CT. METHODS. We performed a 12-institution retrospective cohort study of adult patients who underwent portal venous phase CT for a nonrenal indication. The date of the first CT at each institution ranged from January 1, 2008, to January 1, 2014. Consecutive reports from 12,167 portal venous phase CT examinations were evaluated. Images were reviewed for 4529 CT examinations whose report described a focal renal mass. Eligible masses were 10-40 mm, well-defined, subjectively homogeneous, and 21-39 HU. Of these, masses that were shown to be solid without macroscopic fat; classified as Bosniak IIF, III, or IV; or confirmed to be malignant were considered clinically important. The reference standard was renal mass protocol CT or MRI, ultrasound of definitively benign cysts or solid masses, single-phase contrast-enhanced CT or unenhanced MRI showing no growth or morphologic change for 5 years or more, or clinical follow-up 5 years or greater. A reference standard was available for 346 masses in 300 patients. The 95% CIs were calculated using the binomial exact method. RESULTS. Eligible masses were identified in 4.2% of patients (514/12,167; 95% CI, 3.9-4.6%). Of 346 masses with a reference standard, none were clinically important (0%; 95% CI, 0-0.9%). Mean mass size was 17 mm; 72% (248/346) measured 21-30 HU, and 28% (98/346) measured 31-39 HU. CONCLUSION. Incidental small homogeneous renal masses measuring 21-39 HU at portal venous phase CT are common and highly likely benign. CLINICAL IMPACT. The change in attenuation threshold signifying the need for additional imaging from greater than 20 HU to greater than 30 HU proposed by the Bosniak classification version 2019 is supported.

Cross-Sectional Imaging Evaluation of Vascular Lesions in the Gastrointestinal Tract and Mesentery.

Gastrointestinal (GI) tract and mesenteric vascular lesions can have various clinical presentations, of which GI bleeding is the most common. This collection of pathology is highly variable in etiology ranging from occlusive disease to vascular malformations to trauma to neoplasms which makes for a challenging workup and diagnosis. The advent of multiple imaging modalities and endoscopic techniques makes the diagnosis of these lesions more achievable, and familiarity with their various imaging findings can have a significant impact on patient management. In this article, we review the gamut of GI tract and mesenteric vascular lesions and their associated imaging findings.

Calcified Adrenal Lesions: Pattern Recognition Approach on Computed Tomography With Pathologic Correlation.

Incidental adrenal lesions are found in 2% to 10% of the population. The presence and pattern of calcifications, in conjunction with other clinical and imaging features, such as soft tissue attenuation, enhancement, and laterality, can aid in narrowing a differential diagnosis, thereby preventing unnecessary biopsies and avoiding delays in management. Calcified adrenal lesions can be categorized under the clinical and laboratory headings of normal adrenal function, hyperfunctioning adrenal tissue, and adrenal insufficiency. In this review, we provide an algorithmic approach to assessing calcified adrenal nodules with correlative radiologic findings.

Lumbosacral plexiform neurofibroma: a rare case in an adult without neurofibromatosis type I.

Plexiform neurofibromas are an uncommon variant of neurofibromas that are described as being essentially pathognomonic of neurofibromatosis type 1 (NF1). Plexiform neurofibromas in the absence of NF1 are extremely rare. We present the case of a 38-year-old woman with a large multilobulated lumbosacral mass extending into the pelvis and proximal thigh. Histopathology of a CT-guided biopsy of the mass revealed it to be a neurofibroma. The imaging findings were consistent with a plexiform subtype. Further imaging and clinical workup showed that the patient had no other identifiable neurofibromas and did not meet criteria for the diagnosis of NF1.

Bleeding Liver Masses: Imaging Features With Pathologic Correlation and Impact on Management.

OBJECTIVE. The purposes of this article are to discuss a variety of liver masses that can present with hemorrhage, including their characteristic imaging features, and to propose a diagnostic approach. CONCLUSION. A broad spectrum of pathologic conditions can present as spontaneous hemorrhage within or surrounding the liver and may present acutely or as a chronic or incidental finding. Imaging characteristics and clinical history can often narrow the differential diagnosis and guide management.

Villous Gastrointestinal Tumors: Multimodality Imaging with Histopathologic Correlation.

Villous lesions are advanced adenomas that manifest most commonly in the colon; however, they can develop throughout the gastrointestinal tract. The duodenum is the most common small-bowel site of these lesions. Although in most cases these are isolated lesions that occur sporadically, patients with certain specific colorectal cancer syndromes, including familial adenomatous polyposis and hereditary nonpolyposis colorectal cancer, may develop multiple advanced adenomas. Villous lesions are important because although they are histologically benign, they may harbor dysplasia and have potential for malignancy. These characteristics make them a primary target for colorectal cancer screening with optical and virtual colonoscopy. However, these lesions can also be symptomatic and detected at diagnostic imaging when patients present for examination. They have characteristic features at a variety of imaging examinations, including barium fluoroscopy, CT, MRI, and endoscopic US. It is important for radiologists to be aware of these lesions, their potential morphologies, and their typical appearances at multimodality imaging. Although villous tumors can be detected at imaging and confirmed with biopsy, owing to limitations in identifying dysplasia and foci of malignancy with the above modalities alone and the potential for malignancy, referral for surgical resection of these lesions ultimately is required. ©RSNA, 2018.

HIV-related Malignancies and Mimics: Imaging Findings and Management.

The risk of developing malignancy is higher in patients with human immunodeficiency virus (HIV) infection than in non-HIV-infected patients. Several factors including immunosuppression, viral coinfection, and high-risk lifestyle choices lead to higher rates of cancer in the HIV-infected population. A subset of HIV-related malignancies are considered to be acquired immunodeficiency syndrome (AIDS)-defining malignancies, as their presence confirms the diagnosis of AIDS in an HIV-infected patient. The introduction of highly active antiretroviral therapy (HAART) has led to a significant drop in the rate of AIDS-defining malignancies, including Kaposi sarcoma, non-Hodgkin lymphoma, and invasive cervical carcinoma. However, non-AIDS-defining malignancies (eg, Hodgkin lymphoma, lung cancer, hepatocellular carcinoma, and head and neck cancers) now account for an increasing number of cancer cases diagnosed in HIV-infected patients. Although the number has decreased, AIDS-defining malignancies account for 15%-19% of all deaths in HIV-infected patients in the post-HAART era. Most HIV-related malignancies in HIV-infected patients manifest at an earlier age with a more aggressive course than that of non-HIV-related malignancies. Understanding common HIV-related malignancies and their specific imaging features is crucial for making an accurate and early diagnosis, which impacts management. Owing to the weakened immune system of HIV-infected patients, other entities such as various infections, particularly opportunistic infections, are prevalent in these patients. These processes can have confounding clinical and imaging manifestations that mimic malignancy. This article reviews the most common AIDS-defining and non-AIDS-defining malignancies, the role of imaging in their diagnosis, and the imaging mimics of malignancies in HIV-infected patients. ©RSNA, 2018.

Nongynecologic Findings Seen at Pelvic US.

Ultrasonography (US) is frequently the first imaging modality used to examine women with symptoms involving the pelvis. It is widely available and involves no exposure to ionizing radiation. Images can be acquired with a transabdominal, endovaginal, or translabial approach, and the use of video clips and three-dimensional reconstructions can be helpful. US is excellent for assessment of the uterus, ovaries, and adnexa. Occasionally, nongynecologic pelvic diseases arising from the gastrointestinal, genitourinary, and musculoskeletal systems and the pelvic peritoneal and extraperitoneal spaces may be detected and can be a source of diagnostic dilemma. US can be helpful not only in the detection but also occasionally in the characterization of such entities. Computed tomography and magnetic resonance imaging are useful in complicated cases. In this article, the normal US appearance of the bowel and US signs of bowel disease and specific entities, including appendicitis, diverticular disease, bowel obstruction, appendiceal mucocele, and intestinal tumors, are reviewed. The lower urinary tract is included in the field of view in every pelvic US examination; commonly encountered entities related to the urinary bladder, distal ureter, and urethra are illustrated. In addition to arising in the gastrointestinal and genitourinary tracts, pathologic conditions in the pelvis can arise in the peritoneal or extraperitoneal space. Although conditions of the pelvic peritoneal and extraperitoneal spaces are rare, it is important to recognize these entities and distinguish them from the more common gynecologic diseases. Owing to the implications for diagnosis and management, radiologists and other physicians who perform pelvic US should be aware of the spectrum of nongynecologic pathologic entities that can be detected. ©RSNA, 2017.

Post-operative complications of cholecystectomy: what the radiologist needs to know.

Cholecystectomy is one of the most performed surgical procedures. The safety of this surgery notwithstanding, the sheer volume of operations results in a notable incidence of post-cholecystectomy complications. Early and accurate diagnosis of such complications is essential for timely and effective management. Imaging techniques are critical for this purpose, aiding in distinguishing between expected postsurgical changes and true complications. This review highlights current knowledge on the indications for cholecystectomy, pertinent surgical anatomy and surgical technique, and the recognition of anatomical variants that may complicate surgery. The article also outlines the roles of various imaging modalities in identifying complications, the spectrum of possible postsurgical anatomical changes, and the implications of such findings. Furthermore, we explore the array of complications that can arise post-cholecystectomy, such as biliary system injuries, gallstone-related issues, vascular complications, and the formation of postsurgical collections. Radiologists should be adept at identifying normal and abnormal postoperative findings to guide patient management effectively.

Unusual liver tumors: spectrum of imaging findings with pathologic correlation.

The liver is a common location for both primary and secondary cancers of the abdomen. Radiologists become familiar with the typical imaging features of common benign and malignant liver tumors; however, many types of liver tumors are encountered infrequently. Due to the rarity of these lesions, their typical imaging patterns may not be easily recognized, meaning their underlying pathologic features may not be discovered or suggested until an invasive biopsy is performed. In this review article, we discuss multiple hepatic neoplasms that are both unusual and rare. Some have typical imaging patterns, whereas others are non-specific and can only be included in the differential diagnosis. The clinical history and serologic findings are often critical in suggesting these entities; therefore, these are also discussed to familiarize the radiologist with the appropriate clinical setting of each. The article includes an image-rich description of each entity with accompanying figures describing the ultrasonography, computed tomography, and magnetic resonance imaging features of each disease process. Novel therapies and prognosis of several of the diseases are also included in the discussion.

Beyond the GIST: mesenchymal tumors of the stomach.

Intramural gastric masses arise in the wall of the stomach (generally within the submucosa or muscularis propria), often with intact overlying mucosa. These tumors are typically mesenchymal in origin and have overlapping radiologic appearances. A combination of features such as location, attenuation, enhancement, and growth pattern may suggest one diagnosis over another. Gastrointestinal stromal tumors (GISTs) account for the majority of intramural tumors and can vary widely in appearance, from small intraluminal lesions to exophytic masses that protrude into the peritoneal cavity, commonly with areas of hemorrhage or necrosis. A well-circumscribed mass measuring -70 to -120 HU is a lipoma. Leiomyomas usually manifest as low-attenuation masses at the gastric cardia. Homogeneous attenuation is a noteworthy characteristic of schwannomas, particularly for larger lesions that might otherwise be mistaken for GISTs. A hypervascular mass in the antrum is a common manifestation of glomus tumors. Hemangiomas are also hypervascular but often manifest in childhood. Inflammatory fibroid polyps usually arise as a polypoid mass in the antrum. Inflammatory myofibroblastic tumors are infiltrative neoplasms with a propensity for local recurrence. Plexiform fibromyxomas are rare, usually antral tumors. Carcinoid tumors are epithelial in origin, but often submucosal in location, and therefore should be distinguished from other intramural lesions. Multiple carcinoid tumors are associated with hypergastrinemia, either in the setting of chronic atrophic gastritis or Zollinger-Ellison syndrome. Sporadic solitary carcinoid tumors not associated with hypergastrinemia have a higher rate of metastasis. Histopathologic analysis, including immunohistochemistry, is usually required for diagnosis of intramural masses.

Non-Alcoholic Fatty Pancreas Disease: The Unsung Disease.

Non-alcoholic fatty pancreas disease (NAFPD) is a relatively new and emerging disease that is increasingly diagnosed yearly, like non-alcoholic fatty liver disease (NAFLD). It is associated especially with metabolic syndrome and obesity. As awareness of pancreatic steatosis and its clinical implications increase, it is diagnosed more frequently. The researchers have explained the clinical importance of NAFPD and the diseases it causes, such as pancreatitis, pancreatic insufficiency, and pancreatic cancer. Although the definitive treatment is not yet established, the primary treatment approach is weight loss since NAFPD is associated with metabolic syndrome as well as obesity. Although pharmacological agents, such as oral hypoglycemic agents, have been investigated in animal experiments, studies on humans have not been conducted. Since the research on NAFPD is still insufficient, it is a subject that needs to be investigated, and further studies are needed to explore its pathophysiology, clinical impact, and its management.

Superior mesenteric artery thrombosis and small bowel necrosis: An uncommon thromboembolic manifestation in COVID-19 pneumonia.

Thromboembolism is a recognized complication in patients with COVID-19 infection. It is believed that coagulopathy results secondary to severe inflammatory response syndrome with release of cytokines, viral activation of coagulation cascade or viral related vasculitis. Both arterial and venous thromboembolic complications have been described, however venous thromboembolic complications are much far common. We present an uncommon thromboembolic complication of the superior mesenteric artery in a 49-year-old male with COVID-19 pneumonia. The patient also developed segmental infarct of his renal transplant. Patients with SARS-COV-2 infection should be closely evaluated and monitored for the development of thromboembolic complications. Prompt evaluation with CT angiography of suspected thromboembolism could help early diagnosis and treatment which can reflect better patients' outcomes.