Purpose

The purpose of this study was to determine the frequency in which the pelvis component of an abdominopelvic CT provides information that would influence clinical management in two separate groups of patients: those with previously resected pancreatic ductal adenocarcinoma (PDA) and those with locally advanced unresectable PDA.

Methods

This institutional review-board approved HIPAA compliant retrospective study with waived informed consent included 247 subjects with histologically proven PDA, including 153 subjects post-pancreaticoduodenectomy and 94 subjects with locally advanced unresectable disease. Imaging reports interpreted between January 2005 and December 2013 were obtained from our institution's Radiology Information System by searching a Cancer Registry database of PDA patients separately for the words "whipple" and "unresectable." CT findings were separated by location in the abdomen or pelvis, and subsequently reviewed and graded for their likelihood of representing metastatic disease. The probability of pelvic CT influencing clinical management-i.e., of finding isolated pelvic metastatic disease-was determined using 95% binomial proportion confidence intervals for both the post-pancreaticoduodenectomy and locally advanced unresectable groups.

Results

No subjects who had undergone pancreaticoduodenectomy had an isolated pelvic metastasis on follow-up imaging (0%; 95% CI 0-2.38, p = 0.0004); 33 had metastatic disease in the abdomen, and 120 had no or equivocal evidence of abdominopelvic metastatic disease. One subject with locally advanced unresectable PDA had a possible isolated pelvic metastasis on follow-up imaging (1.1%; 95% CI 0.03-5.79, p = 0.048); 20 had metastatic disease in the abdomen, and 73 had no or equivocal evidence of abdominopelvic metastatic disease.

Conclusion

Isolated pelvic metastatic disease rarely occurs in patients with PDA who have had prior pancreaticoduodenectomy or have a locally advanced unresectable primary tumor, suggesting routine pelvic CT in follow-up imaging of these patients may not be necessary.

Rett syndrome (RTT) is a severe neurodevelopmental disorder primarily caused by heterozygous loss-of-function mutations in the X-linked gene MECP2 that is a global transcriptional regulator. Mutations in the methyl-CpG binding domain (MBD) of MECP2 disrupt its interaction with methylated DNA. Here, we investigate the effect of a novel MECP2 L124W missense mutation in the MBD of an atypical RTT patient with preserved speech in comparison to severe MECP2 null mutations. L124W protein had a limited ability to disrupt heterochromatic chromocenters due to decreased binding dynamics. We isolated two pairs of isogenic WT and L124W induced pluripotent stem cells. L124W induced excitatory neurons expressed stable protein, exhibited increased input resistance and decreased voltage-gated Na⁺ and K⁺ currents, and their neuronal dysmorphology was limited to decreased dendritic complexity. Three isogenic pairs of MECP2 null neurons had the expected more extreme morphological and electrophysiological phenotypes. We examined development and maturation of L124W and MECP2 null excitatory neural network activity using micro-electrode arrays. Relative to isogenic controls, L124W neurons had an increase in synchronous network burst frequency, in contrast to MECP2 null neurons that suffered a significant decrease in synchronous network burst frequency and a transient extension of network burst duration. A biologically motivated computational neural network model shows the observed changes in network dynamics are explained by changes in intrinsic Na⁺ and K⁺ currents in individual neurons. Our multilevel results demonstrate that RTT excitatory neurons show a wide spectrum of morphological, electrophysiological and circuitry phenotypes that are dependent on the severity of the MECP2 mutation.

Cystic renal cell carcinoma (RCC) is almost certainly overdiagnosed and overtreated. Efforts to diagnose and treat RCC at a curable stage result in many benign neoplasms and indolent cancers being resected without clear benefit. This is especially true for cystic masses, which compared with solid masses are more likely to be benign and, when malignant, less aggressive. For more than 30 years, the Bosniak classification has been used to stratify the risk of malignancy in cystic renal masses. Although it is widely used and still effective, the classification does not formally incorporate masses identified at MRI or US or masses that are incompletely characterized but are highly likely to be benign, and it is affected by interreader variability and variable reported malignancy rates. The Bosniak classification system cannot fully differentiate aggressive from indolent cancers and results in many benign masses being resected. This proposed update to the Bosniak classification addresses some of these shortcomings. The primary modifications incorporate MRI, establish definitions for previously vague imaging terms, and enable a greater proportion of masses to enter lower-risk classes. Although the update will require validation, it aims to expand the number of cystic masses to which the Bosniak classification can be applied while improving its precision and accuracy for the likelihood of cancer in each class.