Gracilis Flap Reconstruction After Proctocolectomy for Malignancy and Inflammatory Bowel Disease.

BACKGROUND: Gracilis flap reconstruction (GFR) following abdominoperineal resection (APR) or proctocolectomy (PC) can reduce pelvic wound complications but has not been adequately assessed in the setting of immunosuppression, fistulous disease, and neoadjuvant chemoradiation. METHODS: Patients undergoing APR/PC with GFR were retrospectively analyzed with regard to perioperative characteristics, and morbidity was assessed. RESULTS: Patients underwent GFR for rectal cancer (n = 28), anal cancer (n = 3), inflammatory bowel disease (n = 13), or benign fistulizing disease (n = 1). 22.2% were chronically immunosuppressed, and 66.7% underwent preoperative chemoradiation. Twenty (44.4%) patients had minor wound complications, all treated nonoperatively. Nine patients had major complications with 4 patients requiring reoperation. The 4 threatened flaps were unilateral, and all were salvaged. Donor site morbidity was minimal. Patients with major complications were older (56 vs. 71 years, P = .030), and less likely to have pelvic drains (P = .018). CONCLUSION: In high-risk perineal wounds, GFR offers durable reconstruction with acceptably low morbidity.

The Impact of an Enhanced Recovery Protocol in a High-Risk Population Undergoing Colon Cancer Surgery.

OBJECTIVE: Enhanced Recovery ERP protocols (ERP) have improved surgical outcomes in patients undergoing elective colon cancer (CC) surgery; however, efficacy in different populations may vary. We examined the impact of an ERP in a population with high rates of obesity and multiple comorbidities. METHODS: We performed a retrospective analysis of factors associated with postoperative complications (PoC) and length of stay (LOS) following CC surgery from 2011 to 2019 in a 5-hospital healthcare system which serves a population with higher rates of obesity (body mass index ≥30kg/m2) and multi-comorbidities, as compared to published studies. Univariable and multivariable analyses were performed. RESULTS: A total of 408 elective CC surgery patients with complete oncologic surgical data were identified. Of these, 191 (46.81%) were under ERP. Factors independently associated with PoC included obesity (OR=1.66, P=.029), laparoscopic (OR=.52, P=.020), and hybrid (OR=.38, P=.012) versus open surgery and ASA (American Society of Anesthesiologists) class ≥3 (OR=1.98, P=.006). ERP did not impact PoC but was associated with a reduction in LOS (ß=-1.02 days, 95%CI: -1.75 - -.30, P=.006). ERP had an impact on LOS in both the non-obese and obese groups (P<.001 and P=.034, respectively). PoC significantly increased LOS (ß=6.67 days, 95%CI: 5.41-7.03, P<.001). CONCLUSIONS: Following elective CC surgery, obesity and medical comorbidities were associated with increased PoC and in turn, as expected, increased LOS. ERP was associated with a reduction in LOS in both obese and non-obese patients. In high-risk populations, application of ERP may be particularly important to optimize surgical outcomes following CC surgery.

Sugarbaker Versus Keyhole Repair for Parastomal Hernia: a Systematic Review and Meta-analysis of Comparative Studies.

INTRODUCTION: Parastomal hernia is a debilitating complication of stoma creation. Parastomal hernia repair with mesh reduces recurrence rates in open and laparoscopic settings. Recent comparative studies conflict with previously pooled data on optimal mesh repair technique. The objective of this study is to examine parastomal hernia recurrence rates after Sugarbaker and keyhole repairs by performing an updated systematic review and meta-analysis of comparative studies. METHODS: A systematic review of PubMed, MEDLINE, EMBASE, the Cochrane database, SCOPUS, and the PROSPERO registry was performed according to PRISMA 2020 guidelines (PROSPERO ID: CRD42021290483). Studies comparing parastomal hernia recurrences after Sugarbaker and keyhole repairs were included. Studies with overlapping patient cohorts (duplicate data), non-comparative studies, studies that did not report the primary outcome of interest, and studies not in the English language were excluded. Study bias was assessed using the Newcastle-Ottawa scale. Pooled mean differences (MD), odds ratios (OR), and risk ratios (RR) with 95% confidence intervals (CI) were calculated. Heterogeneity was assessed using the I2 statistic. Forest plots and funnel plots were generated. Study quality was analyzed using MINORS. Additional subgroup analysis of modern studies was performed. RESULTS: Ten comparative studies published between 2005 and 2021 from 5 countries were included for analysis comprising 347 Sugarbaker repairs and 246 keyhole repairs. There were no differences in patient age, sex, or BMI between the groups. There was no difference between the groups regarding surgical site infection (OR 0.78; CI 0.31-1.98; P = 0.61) or post-operative bowel obstruction (OR 0.76; CI 0.23-2.56; P = 0.66). Sugarbaker repairs were significantly less often associated with parastomal hernia recurrence when compared to keyhole repairs (OR 0.38; CI 0.18-0.78; P = 0.008). There was no significant heterogeneity among the studies comparing parastomal hernia recurrence (I2 = 32%; P = 0.15). Quality analysis revealed a median MINORS score of 11 (range 6-16). Subgroup analysis of studies performed after the previously published pooled analysis (2015-2021) revealed no significant difference in parastomal hernia recurrence between the two groups (OR 0.58; CI 0.24-1.38; P = 0.22) with a significant subgroup effect (P = 0.05). CONCLUSIONS: Though there were lower rates of parastomal hernia recurrence with Sugarbaker repairs on overall analysis, this phenomenon disappeared on subgroup analysis of modern studies. Randomized controlled trials with contemporary cohorts would help further evaluate these repairs and minimize potential bias.

Clinical Characteristics and Outcomes of Colorectal Cancer in the ColoCare Study: Differences by Age of Onset.

Early-onset colorectal cancer has been on the rise in Western populations. Here, we compare patient characteristics between those with early- (<50 years) vs. late-onset (≥50 years) disease in a large multinational cohort of colorectal cancer patients (n = 2193). We calculated descriptive statistics and assessed associations of clinicodemographic factors with age of onset using mutually-adjusted logistic regression models. Patients were on average 60 years old, with BMI of 29 kg/m2, 52% colon cancers, 21% early-onset, and presented with stage II or III (60%) disease. Early-onset patients presented with more advanced disease (stages III-IV: 63% vs. 51%, respectively), and received more neo and adjuvant treatment compared to late-onset patients, after controlling for stage (odds ratio (OR) (95% confidence interval (CI)) = 2.30 (1.82-3.83) and 2.00 (1.43-2.81), respectively). Early-onset rectal cancer patients across all stages more commonly received neoadjuvant treatment, even when not indicated as the standard of care, e.g., during stage I disease. The odds of early-onset disease were higher among never smokers and lower among overweight patients (1.55 (1.21-1.98) and 0.56 (0.41-0.76), respectively). Patients with early-onset colorectal cancer were more likely to be diagnosed with advanced stage disease, to have received systemic treatments regardless of stage at diagnosis, and were less likely to be ever smokers or overweight.

Harmonized and high-quality datasets of aerosol optical depth at a US continental site, 1997-2018.

Aerosol optical depth (AOD) characterizes the aerosol burden in the atmosphere, while its wavelength dependence is a sign of particle size. Long-term records of wavelength-resolved AOD with high quality and suitable continuity are required for climate change assessment. Typically, climate-related studies use AOD products provided by several, and perhaps different, ground-based instruments. The measurements from these instruments often have different accuracy and temporal resolution. To preserve the advantages of these products (high quality) and to reduce their disadvantages (patchy records), we generate a merged dataset obtained from four instruments deployed at a US continental site in which a nearly-continuous AOD record is found at two wavelengths (500 and 870 nm) with high quality and high temporal resolution (1-min) for a 21-yr period (1997-2018). The combined dataset addresses: (1) varying data quality and resolution mismatch of the individual AOD records, and (2) the uncertainty of the merged AOD and its relevance for user-specified needs. The generated dataset will be beneficial for a wide range of applications including aerosol-radiation interactions.

Adherence to neoadjuvant therapy guidelines for locally advanced rectal cancers in a region with sociodemographic disparities.

BACKGROUND: Practice guidelines recommend neoadjuvant chemoradiation (NCR) for locally advanced rectal cancer (LARC). We examined guideline adherence in a healthcare system serving a region with socioeconomic disparities and poor cancer outcomes. METHODS: Retrospective analysis of factors associated with guideline adherence. RESULTS: 63.1% of stage II/III LARC patients received NCR. Factors associated with adherence included white race (OR = 2.15, p = 0.024), private insurance (OR = 2.70, p = 0.005), employed status (OR = 2.30, p = 0.031), age at diagnosis (OR = 0.74, p = 0.032), appropriate local staging (OR = 9.17, p < 0.0001), and diagnosis later in the study period (OR per 1 year = 1.20, p = 0.006). By multivariate analysis, private insurance (OR = 2.51, p = 0.023), younger age (OR per 10 years = 0.72, p = 0.048) and appropriate local staging (OR = 6.67, p < 0.0001) were associated with adherence. CONCLUSION: Guideline adherence for LARC in our system is low and is impacted by employment, race and insurance status. Standard of care compliance remains an important target for improvement efforts in this underserved region of the nation's Mid-South.

What Is the Utility of Restaging Imaging for Patients With Clinical Stage II/III Rectal Cancer After Completion of Neoadjuvant Chemoradiation and Prior to Proctectomy?

BACKGROUND: In the United States, patients with clinical stage II or III rectal cancer typically receive neoadjuvant chemoradiation therapy (chemo/XRT) over a 5-6 week period followed by a 6-10 week break prior to proctectomy. In the current study, we evaluate the utilization of restaging studies performed and detection of disease progression during this window. METHODS: A retrospective review of patients with clinical stage II/III rectal cancer was performed. Medical records were analyzed to collect clinicopathologic data and the performance and results of preoperative, early postoperative, and first surveillance CT and/or PET/CT in patients completing long course neoadjuvant chemo/XRT and undergoing proctectomy. RESULTS: Between 2005 and 2017, 176 patients with clinical stage II or III rectal adenocarcinoma completed neoadjuvant chemo/XRT and underwent proctectomy. Preoperative restaging with CT CAP and/or CT/PET was performed in 72 (40.9%) patients with no detection of disease progression. Of the 104 patients without preoperative restaging, 1 had intraoperative detection of liver metastases and 31 had early postoperative reimaging (within 30 days of proctectomy) of which 2 had detection of new pulmonary metastases. Among 72 patients with no preoperative or early postoperative reimaging, first surveillance imaging was available in 47 and detected new metastases in 8 (17%). DISCUSSION: In patients with clinical stage II/III rectal cancer who undergo long course neoadjuvant chemo/XRT, perioperative reimaging with CT CAP and/or PET/CT detects new metastases in a small percentage of patients. A multi-institutional, prospective analysis using standardized staging protocols is warranted to better determine the value of preoperative restaging in these patients.

Restaging Patients with Rectal Cancer Following Neoadjuvant Chemoradiation: A Systematic Review.

BACKGROUND: In the USA, most patients with clinical stage II/III rectal cancer receive neoadjuvant chemoradiation (chemo/XRT) over 5-6 weeks followed by a 6-10-week break before proctectomy. As chemotherapy is delivered at radio-sensitizing doses, there is essentially a 3-month window during which potential systemic disease is untreated. Evidence regarding the utility of restaging patients prior to proctectomy is limited. METHODS: PubMed, Scopus, Web of Science, and the Cochrane Library were searched for studies evaluating the utility of restaging patients with rectal cancer after completion of long-course chemo/XRT, and reporting associated changes in management. Studies that were non-English, included <50 patients, or examining the diagnostic accuracy of imaging modalities were excluded. Study quality was evaluated using the modified Newcastle Ottawa Scale. RESULTS: Eight studies were identified including a total of 1251 patients restaged between completion of chemo/XRT and proctectomy. All studies were retrospective. Restaging identified new metastatic disease in 72 (6.0%) patients, with 4 studies reporting specific sites: liver (n = 28), lung (n = 8), adrenal (n = 1), bone (n = 1), and multiple sites (n = 7). Overall progression (distant or local) was detected in 88 (7.0%) patients and resulted in a change in management in 77 (87.5%) of these patients. Tumor-related prognostic characteristics were inconsistently reported among studies, precluding meta-analysis. CONCLUSIONS: Although restaging between completion of neoadjuvant chemo/XRT and proctectomy detects disease progression in only a small percentage of patients, findings alter the treatment plan in the vast majority of these patients. Multi-institutional collaboration with analysis of well-defined prognostic variables may better identify patients most likely to benefit from restaging.

Portal Venous Stenting in Locally Advanced Pancreatic Cancer to Decrease Risk of Thrombosis Before Irreversible Electroporation: A Case Report and Review of the Literature.

Background: For patients with locally advanced pancreatic cancer, irreversible electroporation (IRE) is a fairly novel treatment tool that has shown promise in improving survival. However, many patients being considered for IRE have tumors adjacent to and/or encasing portal vasculature, increasing risk of postoperative portal vein thrombosis and associated complications. This report describes a successful new approach of portal venous stenting preoperatively to decrease this risk. Case Presentation: A 64-year-old female with locally advanced pancreatic cancer, initially deemed too high risk for IRE therapy because of portal vein-superior mesenteric vein confluence encasement and compression, was offered and underwent venous stenting to decrease the chance of postoperative thrombosis and related complications. Stenting improved portal venous flow, decreased collateralization, and allowed for successful IRE. At 61 days post-IRE, there was no significant tumor growth and the stent remained patent. Conclusion: Preoperative portomesenteric stenting could expand the population eligible for IRE therapy, allowing for this treatment in patients without other options. To the authors' knowledge, this is the first reported case of portal venous stenting for this purpose.

Neuromagnetic oscillations predict evoked-response latency delays and core language deficits in autism spectrum disorders.

Previous studies have observed evoked response latency as well as gamma band superior temporal gyrus (STG) auditory abnormalities in individuals with autism spectrum disorders (ASD). A limitation of these studies is that associations between these two abnormalities, as well as the full extent of oscillatory phenomena in ASD in terms of frequency and time, have not been examined. Subjects were presented pure tones at 200, 300, 500, and 1,000 Hz while magnetoencephalography assessed activity in STG auditory areas in a sample of 105 children with ASD and 36 typically developing controls (TD). Findings revealed a profile such that auditory STG processes in ASD were characterized by pre-stimulus abnormalities across multiple frequencies, then early high-frequency abnormalities followed by low-frequency abnormalities. Increased pre-stimulus activity was a 'core' abnormality, with pre-stimulus activity predicting post-stimulus neural abnormalities, group membership, and clinical symptoms (CELF-4 Core Language Index). Deficits in synaptic integration in the auditory cortex are associated with oscillatory abnormalities in ASD as well as patient symptoms. Increased pre-stimulus activity in ASD likely demonstrates a fundamental signal-to-noise deficit in individuals with ASD, with elevations in oscillatory activity suggesting an inability to maintain an appropriate 'neural tone' and an inability to rapidly return to a resting state prior to the next stimulus.

Missing and delayed auditory responses in young and older children with autism spectrum disorders.

BACKGROUND: The development of left and right superior temporal gyrus (STG) 50 ms (M50) and 100 ms (M100) auditory responses in typically developing (TD) children and in children with autism spectrum disorder (ASD) was examined. Reflecting differential development of primary/secondary auditory areas and supporting previous studies, it was hypothesized that whereas left and right M50 STG responses would be observed equally often in younger and older children, left and right M100 STG responses would more often be absent in younger than older children. In ASD, delayed neurodevelopment would be indicated via the observation of a greater proportion of ASD than TD subjects showing missing M100 but not M50 responses in both age groups. Missing M100 responses would be observed primarily in children with ASD with language impairment (ASD + LI) (and perhaps concomitantly lower general cognitive abilities). METHODS: Thirty-five TD controls, 63 ASD without language impairment (ASD - LI), and 38 ASD + LI were recruited. Binaural tones were presented. The presence or absence of a STG M50 and M100 was scored. Subjects were grouped into younger (6-10 years old) and older groups (11-15 years old). RESULTS: Although M50 responses were observed equally often in older and younger subjects and equally often in TD and ASD, left and right M50 responses were delayed in ASD - LI and ASD + LI. Group comparisons showed that in younger subjects M100 responses were observed more often in TD than ASD + LI (90 versus 66%, p = 0.04), with no differences between TD and ASD - LI (90 versus 76%, p = 0.14) or between ASD - LI and ASD + LI (76 versus 66%, p = 0.53). In older subjects, whereas no differences were observed between TD and ASD + LI, responses were observed more often in ASD - LI than ASD + LI. Findings were similar when splitting the ASD group into lower- and higher-cognitive functioning groups. CONCLUSION: Although present in all groups, M50 responses were delayed in ASD. Examining the TD data, findings indicated that by 11 years, a right M100 should be observed in 100% of subjects and a left M100 in 80% of subjects. Thus, by 11 years, lack of a left and especially right M100 offers neurobiological insight into sensory processing that may underlie language or cognitive impairment.

The fusiform response to faces: explicit versus implicit processing of emotion.

Regions of the fusiform gyrus (FG) respond preferentially to faces over other classes of visual stimuli. It remains unclear whether emotional face information modulates FG activity. In the present study, whole-head magnetoencephalography (MEG) was obtained from fifteen healthy adults who viewed emotionally expressive faces and made button responses based upon emotion (explicit condition) or age (implicit condition). Dipole source modeling produced source waveforms for left and right primary visual and left and right fusiform areas. Stronger left FG activity (M170) to fearful than happy or neutral faces was observed only in the explicit task, suggesting that directed attention to the emotional content of faces facilitates observation of M170 valence modulation. A strong association between M170 FG activity and reaction times in the explicit task provided additional evidence for a role of the fusiform gyrus in processing emotional information.

The human visual cortex responds to gene therapy-mediated recovery of retinal function.

Leber congenital amaurosis (LCA) is a rare degenerative eye disease, linked to mutations in at least 14 genes. A recent gene therapy trial in patients with LCA2, who have mutations in RPE65, demonstrated that subretinal injection of an adeno-associated virus (AAV) carrying the normal cDNA of that gene (AAV2-hRPE65v2) could markedly improve vision. However, it remains unclear how the visual cortex responds to recovery of retinal function after prolonged sensory deprivation. Here, 3 of the gene therapy trial subjects, treated at ages 8, 9, and 35 years, underwent functional MRI within 2 years of unilateral injection of AAV2-hRPE65v2. All subjects showed increased cortical activation in response to high- and medium-contrast stimuli after exposure to the treated compared with the untreated eye. Furthermore, we observed a correlation between the visual field maps and the distribution of cortical activations for the treated eyes. These data suggest that despite severe and long-term visual impairment, treated LCA2 patients have intact and responsive visual pathways. In addition, these data suggest that gene therapy resulted in not only sustained and improved visual ability, but also enhanced contrast sensitivity.

Auditory magnetic mismatch field latency: a biomarker for language impairment in autism.

BACKGROUND: Auditory processing abnormalities are frequently observed in autism spectrum disorders (ASD), and these abnormalities may have sequelae in terms of clinical language impairment (LI). The present study assessed associations between language impairment and the amplitude and latency of the superior temporal gyrus magnetic mismatch field (MMF) in response to changes in an auditory stream of tones or vowels. METHODS: Fifty-one children with ASD, and 27 neurotypical control subjects, all aged 6 to 15 years, underwent neuropsychological evaluation, including tests of language function, as well as magnetoencephalographic recording during presentation of tones and vowels. The MMF was identified in the difference waveform obtained from subtraction of responses to standard from deviant stimuli. RESULTS: Magnetic mismatch field latency was significantly prolonged (p < .001) in children with ASD, compared with neurotypical control subjects. Furthermore, this delay was most pronounced (∼50 msec) in children with concomitant LI, with significant differences in latency between children with ASD with LI and those without (p < .01). Receiver operator characteristic analysis indicated a sensitivity of 82.4% and specificity of 71.2% for diagnosing LI based on MMF latency. CONCLUSIONS: Neural correlates of auditory change detection (the MMF) are significantly delayed in children with ASD, and especially those with concomitant LI, suggesting a neurobiological basis as well as a clinical biomarker for LI in ASD.

MEG detection of delayed auditory evoked responses in autism spectrum disorders: towards an imaging biomarker for autism.

Motivated by auditory and speech deficits in autism spectrum disorders (ASD), the frequency dependence of superior temporal gyrus (STG) 50 msec (M50) and 100 msec (M100) neuromagnetic auditory evoked field responses in children with ASD and typically developing controls were evaluated. Whole-cortex magnetoencephalography (MEG) was obtained from 17 typically developing children and 25 children with ASD. Subjects were presented tones with frequencies of 200, 300, 500, and 1,000 Hz, and left and right STG M50 and M100 STG activity was examined. No M50 latency or amplitude Group differences were observed. In the right hemisphere, a Group x Frequency ANOVA on M100 latency produced a main effect for Group (P=0.01), with an average M100 latency delay of 11 msec in children with ASD. In addition, only in the control group was the expected association of earlier M100 latencies in older than younger children observed. Group latency differences remained significant when hierarchical regression analyses partialed out M100 variance associated with age, IQ, and language ability (all P-values <0.05). Examining the right-hemisphere 500 Hz condition (where the largest latency differences were observed), a sensitivity of 75%, a specificity of 81%, and a positive predictive value (PPV) of 86% was obtained at a threshold of 116 msec. The M100 latency delay indicates disruption of encoding simple sensory information. Given similar findings in language impaired and non-language impaired ASD subjects, a right-hemisphere M100 latency delay appears to be an electrophysiological endophenotype for autism.