What is the optimum post treatment surveillance imaging protocol for low-grade appendiceal mucinous neoplasms and pseudomyxoma peritoneii?

Appendiceal mucinous neoplasms are rare and can be associated with the development of disseminated peritoneal disease known as pseudomyxoma peritonei (PMP). Mucinous tumours identified on appendicectomy are therefore followed up to assess for recurrence and the development of PMP. In addition, individuals who initially present with PMP and are treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) are followed up to assess for recurrence. However, despite the concerted efforts of multiple expert groups, the optimal imaging follow-up protocol is yet to be established. The purpose of this article is to review the available evidence for imaging surveillance in these populations to identify the optimum post-resection imaging follow-up protocol.

Common mitochondrial deletions in RNA-Seq: evaluation of bulk, single-cell, and spatial transcriptomic datasets.

Common mitochondrial DNA (mtDNA) deletions are large structural variants in the mitochondrial genome that accumulate in metabolically active tissues with age and have been investigated in various diseases. We applied the Splice-Break2 pipeline (designed for high-throughput quantification of mtDNA deletions) to human RNA-Seq datasets and describe the methodological considerations for evaluating common deletions in bulk, single-cell, and spatial transcriptomics datasets. A robust evaluation of 1570 samples from 14 RNA-Seq studies showed: (i) the abundance of some common deletions detected in PCR-amplified mtDNA correlates with levels observed in RNA-Seq data; (ii) RNA-Seq library preparation method has a strong effect on deletion detection; (iii) deletions had a significant, positive correlation with age in brain and muscle; (iv) deletions were enriched in cortical grey matter, specifically in layers 3 and 5; and (v) brain regions with dopaminergic neurons (i.e., substantia nigra, ventral tegmental area, and caudate nucleus) had remarkable enrichment of common mtDNA deletions.

The role of radiology in addressing the challenge of lung cancer after lung transplantation.

The importance of lung cancer as a complication of lung transplantation is increasingly recognised. It may become an important survival-limiting factor in lung transplant patients as management of other complications continues to improve and utilisation of extended criteria donors grows. Radiology can play a key role in tackling this issue at multiple stages in the transplantation pathway and follow-up process. Routine chest CT as part of pre-transplant recipient assessment (and donor assessment if available) can identify suspicious lung lesions with high sensitivity and detect chronic structural lung diseases such as pulmonary fibrosis associated with an increased risk of malignancy post-transplant. Pre-transplant CT also provides a comparison for later CT studies in the assessment of nodules or masses. The potential role of regular chest CT for lung cancer screening after transplantation is less certain due to limited available evidence on its efficacy. Radiologists should be cognisant of how the causes of pulmonary nodules in lung transplant patients may differ from the general population, vary with time since transplantation and require specific recommendations for further investigation/follow-up as general guidelines are not applicable. As part of the multidisciplinary team, radiology is involved in an aggressive diagnostic and therapeutic management approach for nodular lung lesions after transplant both through follow-up imaging and image-guided tissue sampling. This review provides a comprehensive overview of available clinical data and evidence on lung cancer in lung transplant recipients, and in particular an assessment of the current and potential roles of pre- and post-transplant imaging. KEY POINTS: • Lung cancer after lung transplantation may become an increasingly important survival-limiting factor as mortality from other complications declines. • There are a number of important roles for radiology in tackling the issue which include pre-transplant CT and supporting an aggressive multidisciplinary management strategy where lung nodules are detected in transplant patients. • The introduction of routine surveillance chest CT after transplant in addition to standard clinical follow-up as a means of lung cancer screening should be considered.

Peritoneal malignancy: anatomy, pathophysiology and an update on modern day imaging.

With increasing subspecialised experience in radical cytoreductive surgery and intra-abdominal chemotherapy for peritoneal malignancy, outcomes have improved significantly in selected patients. The surgery and the treatment regimens are radical and therefore correct patient selection is critical. The radiologist plays a central role in this process by estimating, as precisely as possible, the pre-treatment disease burden. Because of the nature of the disease process, accurate staging is not an easy task. Tumour deposits may be very small and in locations where they are very difficult to detect. It must be acknowledged that no form of modern day imaging has the capability of detecting the smallest peritoneal nodules, which may only be visible to direct inspection or histopathological evaluation. Nonetheless, it behoves the radiologist to be as exact and precise as possible in the reporting of this disease process. This is both to select patients who are likely to benefit from radical treatment, and just as importantly, to identify patients who are unlikely to achieve adequate cytoreductive outcomes. In this review, we outline the patterns of spread of disease and the anatomic basis for this, as well as the essential aspects of reporting abdominal studies in this patient group. We provide an evidence-based update on the relative strengths and limitations of our available multimodality imaging techniques namely CT, MRI and positron emission tomography/CT.

An abbreviated MRI protocol for surveillance of cystic pancreatic lesions.

PURPOSE: Cystic pancreatic lesions (CPLs) are common and increasingly encountered in clinical radiology practice. The appropriate imaging surveillance strategy for lower-risk CPLs (branch duct-intraductal papillary mucinous neoplasms and indeterminant small cystic lesions) has been a topic of intense study and debate in recent years. MRI is considered the investigation of choice for initial characterisation and follow-up of CPLs. Follow-up intervals for CPLs vary from 6 months to 2 years and surveillance may be lifelong or until the patient is no longer considered fit for potential surgical intervention. This creates a significant burden on MRI resources as a standard protocol pancreatic MRI may have an acquisition time of up to 35-50 min. However, the necessity of contrast-enhanced sequences and diffusion weighted imaging (DWI) for routine follow-up of CPLs has been questioned in recent years. METHODS: We reviewed the available evidence to determine whether an abbreviated MRI (A-MRI) protocol may be safely adopted for surveillance of CPLs, as has been implemented in other clinical scenarios. RESULTS: A number of recent retrospective studies have indicated that an A-MRI, omitting contrast-enhanced and DWI, may be used for CPL surveillance without any suspicious features or cases of malignancy being missed. Although small number of cases may need to be recalled for additional MR sequences based on the A-MRI findings, there is still a significant overall timesaving. CONCLUSION: The best available evidence currently suggests that an A-MRI protocol should be considered for routine surveillance of CPLs. Prospective studies are required to ensure the findings reported in these retrospective case studies are backed up in ongoing clinical practice.

Utilizing RNA and outlier analysis to identify an intronic splice-altering variant in AP4S1 in a sibling pair with progressive spastic paraplegia.

We report a likely pathogenic splice-altering AP4S1 intronic variant in two sisters with progressive spastic paraplegia, global developmental delay, shy character, and foot deformities. Sequencing was completed on whole-blood messenger RNA (mRNA) and analyzed for gene expression outliers after exome sequencing analysis failed to identify a causative variant. AP4S1 was identified as an outlier and contained a rare homozygous variant located three bases upstream of exon 5 (NC_000014.8(NM_007077.4):c.295-3C>A). Confirmed by additional RNA-seq, reverse-transcription polymerase chain reaction, and Sanger sequencing, this variant corresponded with exon 5, including skipping, altered isoform usage, and loss of expression from the canonical isoform 2 (NM_001128126.3). Previously, loss-of-function variants within AP4S1 were associated with a quadriplegic cerebral palsy-6 phenotype, AP-4 Deficiency Syndrome. In this study, the inclusion of mRNA-seq allowed for the identification of a previously missed splice-altering variant, and thereby expands the mutational spectrum of AP-4 Deficiency Syndrome to include impacts to some tissue-dependent isoforms.

What the Radiologist Should Know About Treatment of Peritoneal Malignancy.

OBJECTIVE: The purpose of this article is to discuss the role of the radiologist in the treatment of peritoneal cancer, with focus placed on advanced treatment options and selection of patients with resectable disease for whom complete cytoreduction can be achieved. CONCLUSION: Peritoneal cancers traditionally have been associated with significant morbidity and universal mortality; however, the management of such cancers has evolved substantially. Advanced treatment options, including cytoreductive surgery and intraperitoneal chemotherapy, are associated with significantly improved long-term patient survival. To ensure that patients benefit from aggressive multimodality treatments, the radiologist plays a pivotal role in the multidisciplinary team to ensure careful patient selection, identifying individuals with resectable disease for whom complete cytoreduction can be achieved.

Advanced multimodality imaging of inflammatory bowel disease in 2015: An update.

The diagnosis and effective management of inflammatory bowel disease (IBD) requires a combination clinical, endoscopic, histological, biological, and imaging data. While endoscopy and biopsy remains the gold standard for diagnosis of IBD, imaging plays a central role in the assessment of extra mural disease, in disease surveillance and in the assessment of response to medical treatments, which are often expensive. Imaging is also vital in the detection and diagnosis of disease related complications, both acute and chronic. In this review, we will describe, with illustrative images, the imaging features of IBD in adults, with emphasis on up-to-date imaging techniques focusing predominantly on cross sectional imaging and new magnetic resonance imaging techniques.

Renal Cell Carcinoma: Accuracy of Multidetector Computed Tomography in the Assessment of Renal Sinus Fat Invasion.

PURPOSE: The purpose of this study was to evaluate the accuracy of multidetector computed tomography (MDCT) in the preoperative assessment of renal sinus fat invasion (RSFI) in patients with renal cell carcinoma (RCC) and to assess imaging features that improve detection of RSFI on CT. METHODS: This is a single-institution retrospective review of 53 consecutive patients with histologically proven RCC who underwent triple-phase preoperative contrast MDCT prior to partial or radical nephrectomy. Two experienced radiologists (R1 and R2), blinded to the final histology result, independently reviewed the preoperative MDCT studies to assess for RSFI. Histopathology was used as the gold standard for the presence of RSFI. RESULTS: Of 55 surgically resected RCCs that were evaluated with contrast-enhanced MDCT, 34.5% (19/55) of RCCs had RSFI on final histopathology. Multidetector CT demonstrated high sensitivity (R1, 100%; R2, 93.7%) for the detection of RSFI, but a low positive predictive value (R1, 40%; R2, 53%) and specificity (R1, 38.4%; R2, 66.6%). Interreader agreement for RSFI was moderate (κ = 0.56). Renal tumors were significantly larger in cases with RSFI (6.3 ± 3.219 cm) than tumors without RSFI (4.1 ± 2.9 cm) (P = 0.0275). Renal sinus fat invasion was more commonly associated to an irregular tumor margin at the tumor renal sinus fat interface (P < 0.001). CONCLUSIONS: Multidetector computed tomography demonstrates a high sensitivity but low positive predictive value in diagnosing RSFI with implications for prognosis and treatment planning. Tumor size, location, irregular tumor margin at the tumor/renal sinus interface, and invasion into pelvicaliceal structures can aid in the diagnosis of RSFI on preoperative MDCT.

Imaging of bone metastasis: An update.

Early detection of skeletal metastasis is critical for accurate staging and optimal treatment. This paper briefly reviews our current understanding of the biological mechanisms through which tumours metastasise to bone and describes the available imaging methods to diagnose bone metastasis and monitor response to treatment. Among the various imaging modalities currently available for imaging skeletal metastasis, hybrid techniques which fuse morphological and functional data are the most sensitive and specific, and positron emission tomography (PET)/computed tomography and PET/magnetic resonance imaging will almost certainly continue to evolve and become increasingly important in this regard.

Evaluation of imaging quality of pulmonary 64-MDCT angiography in pregnancy and puerperium.

OBJECTIVE: The aim of this study was to quantitatively and qualitatively evaluate pulmonary 64-MDCT angiography image quality in pregnancy and puerperium, compared with female nonpregnant control subjects. MATERIALS AND METHODS: The study group comprised 124 consecutive pregnant and postpartum women and 124 female nonpregnant control subjects who presented with suspected pulmonary embolism. The individual studies were evaluated for subjective and objective diagnostic quality. RESULTS: Objective measurements of the arterial enhancement in the pulmonary trunk and left and right pulmonary arteries found that there was no statistically significant difference in attenuation values between the pregnant and puerperium group and the control group for pulmonary artery opacification. The mean attenuation in the pulmonary trunk was 270.54 HU in the pregnant group, 277.53 HU in the puerperium group, and 293.90 HU in the control group. CONCLUSION: We found no significant difference in diagnostic quality of pulmonary CT angiography using MDCT between the study and control groups. The use of MDCT acquisition, faster injection rates, higher contrast medium concentration, and higher trigger levels may decrease the number of nondiagnostic studies in this population. MDCT may be a worthwhile investigation in the majority of pregnant patients with suspected pulmonary embolism.

PET/CT in the imaging of ovarian Cancer.

Ovarian cancer is responsible for the largest proportion of deaths among patients with gynecologic cancer. This paper discusses fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) in the imaging of ovarian cancer. We discuss and demonstrate how FDG PET/CT can be used to appropriately guide clinical management decisions in patients with ovarian cancer. In particular, FDG PET/CT shows great promise for the preoperative evaluation of women with primary ovarian cancer and for subsequent postoperative assessment for recurrence.

Incidental pulmonary nodules detected on abdominal computed tomography.

OBJECTIVES: To review the characteristics and outcome of incidental pulmonary nodules reported on abdominal computed tomography (CT). METHODS: A database search of abdominal CTs from January 1, 2004, to December 31, 2006, revealed 413 patients with incidental pulmonary nodules and at least one follow-up chest CT. Demographic information, nodule characteristics, and eventual outcome of the nodules were analyzed. RESULTS: Of the 413 patients, 56% had benign nodules, 11% had malignant nodules, and the remaining 33% had insufficient follow-up. There was a statistically significant difference (P < 0.05) in the age of the patients, history of malignancy, and size of the incidental nodule between benign and malignant groups. No malignant nodules were found in patients younger than 59 years who did not have a known or suspected malignancy. CONCLUSION: Small pulmonary nodules (<8 mm) on abdominal CT in patients younger than 50 years with no history of malignancy are unlikely to be malignant.

Brown fat at PET/CT: correlation with patient characteristics.

PURPOSES: To assess the prevalence of brown fat in patients with cancer, compare demographic characteristics of those with and those without brown fat, and correlate these characteristics with the mean and maximum standardized uptake values of brown fat. MATERIALS AND METHODS: This case-control study was institutional review board approved and HIPAA compliant. Informed consent was waived. Reports of 12 195 consecutive positron emission tomography/computed tomography examinations performed in 6867 patients between January 2004 and November 2008 were reviewed for documented fluorodeoxyglucose (FDG) uptake in brown fat (n = 298). Control patients (n = 298) without brown fat were chosen and matched for age, sex, and month and year of examination. Age, sex, weight, body mass index, ethnicity, and examination stage (initial vs restaging) were compared between groups. Paired Student t test, χ(2) test, Pearson correlation coefficient, and analysis of variance were used for statistical analysis. RESULTS: Uptake of FDG in brown fat was demonstrated in 298 of 6867 (4.33%) patients. Prevalence of brown fat was significantly higher in female (5.9% [211 of 3587]) than in male patients (2.65% [87 of 3280]; P < .001). Those with brown fat had significantly lower body weight (147.5 lb ± 3.8 vs 168.61 lb ± 5.0; P < .001) and body mass index (24.3 ± 0.54 vs 27.6 ± 0.77; P < .001) than control patients. There was no significant difference in the prevalence of brown fat among ethnic groups. The maximum standardized uptake value of brown fat had a significant inverse correlation with age (r = -0.3, P < .001). CONCLUSION: Patients with brown fat were more likely to be female and thinner than those without brown fat. Younger patients were more likely to have higher maximum standardized uptake values of brown fat.

Cereblon is a direct protein target for immunomodulatory and antiproliferative activities of lenalidomide and pomalidomide.

Thalidomide and the immunomodulatory drug, lenalidomide, are therapeutically active in hematological malignancies. The ubiquitously expressed E3 ligase protein cereblon (CRBN) has been identified as the primary teratogenic target of thalidomide. Our studies demonstrate that thalidomide, lenalidomide and another immunomodulatory drug, pomalidomide, bound endogenous CRBN and recombinant CRBN-DNA damage binding protein-1 (DDB1) complexes. CRBN mediated antiproliferative activities of lenalidomide and pomalidomide in myeloma cells, as well as lenalidomide- and pomalidomide-induced cytokine production in T cells. Lenalidomide and pomalidomide inhibited autoubiquitination of CRBN in HEK293T cells expressing thalidomide-binding competent wild-type CRBN, but not thalidomide-binding defective CRBN(YW/AA). Overexpression of CRBN wild-type protein, but not CRBN(YW/AA) mutant protein, in KMS12 myeloma cells, amplified pomalidomide-mediated reductions in c-myc and IRF4 expression and increases in p21(WAF-1) expression. Long-term selection for lenalidomide resistance in H929 myeloma cell lines was accompanied by a reduction in CRBN, while in DF15R myeloma cells resistant to both pomalidomide and lenalidomide, CRBN protein was undetectable. Our biophysical, biochemical and gene silencing studies show that CRBN is a proximate, therapeutically important molecular target of lenalidomide and pomalidomide.

Imaging of preoperative liver transplantation in adults: what radiologists should know.

Therapeutic strategies for treating patients with liver failure, particularly optimization of liver transplantation, are constantly being refined, with the goal of improving long-term survival with the lowest risk for toxicity in donors and recipients. Optimal planning for liver transplantation requires a multidisciplinary collaboration between the radiologist, hepatologist, clinical oncologist, and transplant surgeon. Radiologists play an essential role in identifying normal and abnormal variant anatomy and other conditions that may be present, a task that is critical for accurate surgical planning. Radiologists also must understand how their findings affect patient preparation. An awareness of the range of indications for liver transplantation, imaging modalities, and current surgical techniques is important to properly evaluate a patient who may undergo liver transplantation. Establishing a pretransplantation definition of the extent of liver disease and thoroughly evaluating the vascular and biliary anatomy are paramount for proper assessment of potential recipients and donors for liver transplantation.

Interventional radiology in the management of abdominal collections after distal pancreatectomy: a retrospective review.

OBJECTIVE: The purpose of this study was to assess the technical and clinical success and complications of imaging-guided percutaneous catheter drainage of peripancreatic fluid collections after distal pancreatectomy. MATERIALS AND METHODS: Between January 2001 and February 2009, the cases of patients who underwent distal pancreatectomy were selected from a surgical database, and the cases of those who underwent subsequent interventional radiologic percutaneous drainage were identified. Details of percutaneous catheter drainage were recorded, and technical and clinical success was determined. Technical success was defined as successful percutaneous imaging-guided placement of a drainage catheter. Primary clinical success was defined as resolution of peripancreatic fluid collection with percutaneous drainage only. Secondary clinical success was defined as resolution of peripancreatic fluid collection with percutaneous drainage and additional manipulations (i.e., tube repositioning, additional catheter drainage) and no surgical débridement. Multifactor logistic regression analysis was used to identify predictors of drain failure. RESULTS: Between January 2001 and February 2009, 365 patients underwent distal pancreatectomy. Of these, 51 patients (14%; 25 men, 26 women; mean age, 53.4 years; range, 18-81 years) underwent 57 CT-guided percutaneous procedures for drainage of postsurgical peripancreatic fluid collection. The mean interval between surgery and drainage was 23.5 days (median, 17 days; range, 2-120 days), and the mean collection size was 7.3 cm in transverse dimension (median, 6.9 cm; range, 2.3-16 cm). The mean duration of catheter drainage was 39.7 days (median, 24 days; range, 3-220 days). The technical success rate was 100%, primary clinical success rate was 60%, and primary and secondary clinical success rates together were 95%. Three of the 51 patients (6%) needed surgery for definitive management of the collection. One of 51 patients (2%) had a complication of the interventional radiologic procedure. Catheter size and the need for additional catheter manipulation were significantly associated with drainage failure (p < 0.05). CONCLUSION: Catheter drainage of peripancreatic fluid collections after distal pancreatectomy is a technically safe and clinically effective procedure. Although extra manipulations may be needed to achieve clinical success, the combined primary and secondary clinical success rates are high.

Treatment of deep intramuscular and musculoskeletal abscess: experience with 99 CT-guided percutaneous catheter drainage procedures.

OBJECTIVE: The purpose of this article is to describe our experience draining deep muscular and musculoskeletal abscess collections with CT guidance, emphasizing clinicopathologic factors associated with drain failure, and to further analyze patient outcomes according to whether the process involves muscle alone or also involves adjacent bone or joint (skeletal involvement). MATERIALS AND METHODS: The details of percutaneous catheter drainage were retrospectively recorded for all drainages performed over a 9-year period. The technical and clinical successes of percutaneous catheter drainage were determined. Multifactor logistic regression analysis was used to identify predictors of drain failure (malignancy, age, chemotherapy, surgery, infection, complexity, size, days in situ, and skeletal involvement). These parameters were assessed in all patients, those with muscle involvement alone and those with musculoskeletal collections. RESULTS: Eighty-nine of 94 patients underwent one percutaneous drainage procedure and 5 of 94 patients underwent two drainages for a total of 99 drainages in 94 patients (one drainage [n = 89] and two drainages [n = 5]). There were 62 men and 32 women with a mean age of 58.5 years (age range [±SD], 22.3-88.0 ± 16 years). The abscess diameters ranged from 1.8 to 13 cm (mean, 5.3 ± 2.5 cm), volume aspirated ranged from 0 to 200 mL (mean, 45 ± 44 mL), and mean duration of drainage was 16.2 days (range, 2-110 ± 18.7 days). The iliopsoas muscle was the most common site of drainage, accounting for 87.8% of the total. Catheter insertion was possible in all patients, with the muscular component successfully drained in 82% (81/99) overall: 85% (46/54) of those with muscle involvement alone and 77% (35/45) of those with musculoskeletal collections. Catheter drainage and antibiotic administration resulted in 65.6% (65/99) not requiring any surgical intervention and resolution of abnormal white cell count or fevers in 98.8% (79/80) of those with abnormal parameters before treatment. Skeletal infection was associated with increased risk of drainage failure (p = 0.0001). CONCLUSION: Percutaneous imaging-guided musculoskeletal drainage is clinically useful, safe, and effective for draining complex musculoskeletal collections. It is highly effective for draining collections involving muscle alone; however, skeletal infection is associated with a higher risk of drain failure.