Short- and long-term morbidity after Taylor flap (oblique rectus abdominis flap) for perineal reconstruction after abdominoperineal resection: A single-center series of 140 patients.

BACKGROUND: Abdominoperineal resection (APR) leads to a substantial loss of tissue and a high rate of complications. The Taylor flap is a musculocutaneous flap used in reconstruction after APR. OBJECTIVES: We aimed to analyze the short and long-term morbidity of reconstruction with a Taylor flap (oblique rectus abdominis flap) after APR and to identify the risk factors for postoperative complications. METHODS: We retrospectively included all patients who had undergone APR with immediate reconstruction with a Taylor flap in our department between July 2000 and June 2018. Demographics, oncological data, treatment, and short- and long-term morbidity were reviewed. RESULTS: Among the 140 patients included, we identified early minor complications in 42 patients (30%) and 14 early major complications (10%). Total necrosis of the flap requiring its removal occurred in four patients (2.8%). Eleven patients (7.9%) presented with a midline incision hernia, and seven (5%) presented with a subcostal incision hernia. No perineal hernia was found. No risk factors for the complications were identified. CONCLUSION: The Taylor flap is a safe procedure with few complications and limited donor site morbidity. Moreover, it prevents perineal hernias. These results confirm that the Taylor flap is a well-suited procedure for reconstruction after APR.

Human and rat skeletal muscle single-nuclei multi-omic integrative analyses nominate causal cell types, regulatory elements, and SNPs for complex traits.

Skeletal muscle accounts for the largest proportion of human body mass, on average, and is a key tissue in complex diseases and mobility. It is composed of several different cell and muscle fiber types. Here, we optimize single-nucleus ATAC-seq (snATAC-seq) to map skeletal muscle cell-specific chromatin accessibility landscapes in frozen human and rat samples, and single-nucleus RNA-seq (snRNA-seq) to map cell-specific transcriptomes in human. We additionally perform multi-omics profiling (gene expression and chromatin accessibility) on human and rat muscle samples. We capture type I and type II muscle fiber signatures, which are generally missed by existing single-cell RNA-seq methods. We perform cross-modality and cross-species integrative analyses on 33,862 nuclei and identify seven cell types ranging in abundance from 59.6% to 1.0% of all nuclei. We introduce a regression-based approach to infer cell types by comparing transcription start site-distal ATAC-seq peaks to reference enhancer maps and show consistency with RNA-based marker gene cell type assignments. We find heterogeneity in enrichment of genetic variants linked to complex phenotypes from the UK Biobank and diabetes genome-wide association studies in cell-specific ATAC-seq peaks, with the most striking enrichment patterns in muscle mesenchymal stem cells (∼3.5% of nuclei). Finally, we overlay these chromatin accessibility maps on GWAS data to nominate causal cell types, SNPs, transcription factor motifs, and target genes for type 2 diabetes signals. These chromatin accessibility profiles for human and rat skeletal muscle cell types are a useful resource for nominating causal GWAS SNPs and cell types.

Stress Testing Pathology Models with Generated Artifacts.

BACKGROUND: Machine learning models provide significant opportunities for improvement in health care, but their "black-box" nature poses many risks. METHODS: We built a custom Python module as part of a framework for generating artifacts that are meant to be tunable and describable to allow for future testing needs. We conducted an analysis of a previously published digital pathology classification model and an internally developed kidney tissue segmentation model, utilizing a variety of generated artifacts including testing their effects. The artifacts simulated were bubbles, tissue folds, uneven illumination, marker lines, uneven sectioning, altered staining, and tissue tears. RESULTS: We found that there is some performance degradation on the tiles with artifacts, particularly with altered stains but also with marker lines, tissue folds, and uneven sectioning. We also found that the response of deep learning models to artifacts could be nonlinear. CONCLUSIONS: Generated artifacts can provide a useful tool for testing and building trust in machine learning models by understanding where these models might fail.

Anesthesia Assistance in Screening Colonoscopy and Adenoma Detection Rate Among Trainees.

BACKGROUND AND AIMS: The use of anesthesia assistance (AA) for screening colonoscopy has been increasing substantially over the past decade, raising concerns about procedure safety and cost without demonstrating a proven improvement in overall quality indicators such as adenoma detection rate (ADR). The effect of AA on ADR has not been extensively studied among trainees learning colonoscopy. We aimed to determine whether type of sedation used during screening colonoscopy affects trainee ADR. METHODS: Using the electronic endoscopy databases of two hospitals in our medical center, we identified colonoscopies performed by 15 trainees from 2014 through 2018, including all screening examinations in which the cecum was reached. Multivariable logistic regression was used to determine factors associated with adenoma detection. RESULTS: We identified 1420 unique patients who underwent screening colonoscopy by a trainee meeting the inclusion criteria. Of these, 459 (32.3%) were performed with AA. Overall trainee ADR was 39.6%, with ADR increasing from 35.0% in year one of training to 42.8% in year three (p = 0.047). ADR for cases with AA was 37.9%, while ADR for conscious sedation cases was 32.0% (p = 0.374). Despite this 5.9% absolute difference, the use of AA was not associated with finding an adenoma on multivariable analysis when controlling for patient age, sex, smoking status, body mass index, trainee year of training, mean withdrawal time, supervising attending ADR, and bowel preparation quality (OR 0.85; 95% CI 0.67-1.09). CONCLUSIONS: Despite providing the ability to more consistently sedate patients, the use of AA did not affect trainee ADR. These results on trainee ADR and sedation type suggest that the overall lack of association between AA use and ADR is applicable to the trainee setting.

Safety and efficacy of the use of lumen-apposing metal stents in the management of postoperative fluid collections: a large, international, multicenter study.

BACKGROUND: Multiple studies have examined the use of lumen-apposing metal stents (LAMSs) for the drainage of peripancreatic fluid collections. Data on the use of LAMSs for postoperative fluid collections (POFCs) are scarce. POFCs may lead to severe complications without appropriate treatment. We aimed to study the outcomes (technical success, clinical success, rate/severity of adverse events, length of stay, recurrence) of the use of LAMSs for the drainage of POFCs. METHODS: This international, multicenter, retrospective study involved 19 centers between January 2012 and October 2017. The primary outcome was clinical success. Secondary outcomes included technical success and rate/severity of adverse events using the ASGE lexicon. RESULTS: A total of 62 patients were included during the study period. The most common etiology of the POFCs was distal pancreatectomy (46.8 %). The mean (standard deviation) diameter was 84.5 mm (30.7 mm). The most common indication for drainage was infection (48.4 %) and transgastric drainage was the most common approach (82.3 %). Technical success was achieved in 60/62 patients (96.8 %) and clinical success in 57/62 patients (91.9 %) during a median (interquartile range) follow-up of 231 days (90 - 300 days). Percutaneous drainage was needed in 8.1 % of patients. Adverse events occurred intraoperatively in 1/62 patients (1.6 %) and postoperatively in 7/62 (11.3 %). There was no procedure-related mortality. CONCLUSION: This is the largest study on the use of LAMSs for POFCs. It suggests good clinical efficacy and safety of this approach. The use of LAMSs in the management of POFCs is a feasible alternative to percutaneous and surgical drainage.

Biologic Significance of Magnetic Resonance Imaging Invisibility in Localized Prostate Cancer.

PURPOSE: Multiparametric magnetic resonance imaging (mpMRI) is used widely for prostate cancer (PCa) evaluation. Approximately 35% of aggressive tumors, however, are not visible on mpMRI. We sought to identify the molecular alterations associated with mpMRI-invisible tumors and determine whether mpMRI visibility is associated with PCa prognosis. METHODS: Discovery and validation cohorts included patients who underwent mpMRI before radical prostatectomy and were found to harbor both mpMRI-visible (Prostate Imaging and Reporting Data System 3 to 5) and -invisible (Prostate Imaging and Reporting Data System 1 or 2) foci on surgical pathology. Next-generation sequencing was performed to determine differential gene expression between mpMRI-visible and -invisible foci. A genetic signature for tumor mpMRI visibility was derived in the discovery cohort and assessed in an independent validation cohort. Its association with long-term oncologic outcomes was evaluated in a separate testing cohort. RESULTS: The discovery cohort included 10 patients with 26 distinct PCa foci on surgical pathology, of which 12 (46%) were visible and 14 (54%) were invisible on preoperative mpMRI. Next-generation sequencing detected prioritized genetic mutations in 14 (54%) tumor foci (n = 8 mpMRI visible, n = 6 mpMRI invisible). A nine-gene signature (composed largely of cell organization/structure genes) associated with mpMRI visibility was derived (area under the curve = 0.89), and the signature predicted MRI visibility with 75% sensitivity and 100% specificity (area under the curve = 0.88) in the validation cohort. In the testing cohort (n = 375, median follow-up 8 years) there was no significant difference in biochemical recurrence, distant metastasis, or cancer-specific mortality in patients with predicted mpMRI-visible versus -invisible tumors (all P > .05). CONCLUSION: Compared with mpMRI-invisible disease, mpMRI-visible tumors are associated with underexpression of cellular organization genes. mpMRI visibility does not seem to be predictive of long-term cancer outcomes, highlighting the need for biopsy strategies that detect mpMRI-invisible tumors.

Transcriptomic heterogeneity in multifocal prostate cancer.

BACKGROUND: Commercial gene expression assays are guiding clinical decision making in patients with prostate cancer, particularly when considering active surveillance. Given heterogeneity and multifocality of primary prostate cancer, such assays should ideally be robust to the coexistence of unsampled higher grade disease elsewhere in the prostate in order to have clinical utility. Herein, we comprehensively evaluated transcriptomic profiles of primary multifocal prostate cancer to assess robustness to clinically relevant multifocality. METHODS: We designed a comprehensive, multiplexed targeted RNA-sequencing assay capable of assessing multiple transcriptional classes and deriving commercially available prognostic signatures, including the Myriad Prolaris Cell Cycle Progression score, the Oncotype DX Genomic Prostate Score, and the GenomeDX Decipher Genomic Classifier. We applied this assay to a retrospective, multi-institutional cohort of 156 prostate cancer samples. Derived commercial biomarker scores for 120 informative primary prostate cancer samples from 44 cases were determined and compared. RESULTS: Derived expression scores were positively correlated with tumor grade (rS = 0.53-0.73; all P < 0.001), both within the same case and across the entire cohort. In cases of extreme grade-discordant multifocality (co-occurrence of grade group 1 [GG1] and ≥GG4 foci], gene expression scores were significantly lower in low- (GG1) versus high-grade (≥GG4) foci (all P < 0.001). No significant differences in expression scores, however, were observed between GG1 foci from prostates with and without coexisting higher grade cancer (all P > 0.05). CONCLUSIONS: Multifocal, low-grade and high-grade prostate cancer foci exhibit distinct prognostic expression signatures. These findings demonstrate that prognostic RNA expression assays performed on low-grade prostate cancer biopsy tissue may not provide meaningful information on the presence of coexisting unsampled aggressive disease. FUNDING: Prostate Cancer Foundation, National Institutes of Health (U01 CA214170, R01 CA183857, University of Michigan Prostate Specialized Program of Research Excellence [S.P.O.R.E.] P50 CA186786-05, Weill Cornell Medicine S.P.O.R.E. P50 CA211024-01A1), Men of Michigan Prostate Cancer Research Fund, University of Michigan Comprehensive Cancer Center core grant (2-P30-CA-046592-24), A. Alfred Taubman Biomedical Research Institute, and Department of Defense.

The Use of Biomarkers in the Risk Stratification of Cystic Neoplasms.

Cyst fluid biomarkers may be used to identify pancreatic cyst subtypes. Biomarkers are selected based on their ability to accurately distinguish mucinous from nonmucinous cysts and to risk stratify cysts based on malignant potential. Biomarkers of interest include but are not limited to amylase, oncogenes, DNA analysis, and epigenetic markers. The introduction of next-generation sequencing and molecular panels has aided in improved diagnostic accuracy and risk stratification. This review presents the diagnostic performance of currently available biomarkers and proposes an algorithm to incorporate their use in the diagnosis of pancreatic cysts.

Efficacy and safety of therapeutic ERCP in patients with cirrhosis: a large multicenter study.

BACKGROUND AND AIMS: Patients with cirrhosis may be less than optimal candidates for ERCP because of underlying ascites, coagulopathy, encephalopathy, and other problems. Although the risks of surgery in patients with cirrhosis are well known, few data are available regarding ERCP in patients with cirrhosis. We performed a retrospective, multicenter study of ERCP in patients with cirrhosis to evaluate outcomes, efficacy, and safety. METHODS: Multicenter retrospective study. RESULTS: A total of 538 ERCP procedures were performed on 328 patients with cirrhosis. A total of 229 patients had Child-Pugh (CP) class A, 229 patients had CP class B, and 80 patients had CP class C. Thrombocytopenia and coagulopathy were corrected before ERCP. The 30-day, procedure-related adverse events included post-ERCP pancreatitis (n = 25, 4.6%: 21 mild, 3 moderate, 1 severe), hemorrhage (n = 6, 1.1%), cholangitis (n = 15, 2.8%), perforation (n = 2, 0.4%), aspiration pneumonia (n = 5, 0.9%), bile leakage (n = 1, 0.2%), cholecystitis (n = 1, 0.2%), and death (n = 1, 0.2%). There was a higher incidence of adverse events in patients with CP class B and C disease when compared with those with CP class A disease (11.4%, 11.3%, and 6.1%, respectively; P = .048). There was no correlation between the risk of significant hemorrhage and the presence of coagulopathy or CP class, even in those who underwent a sphincterotomy. The presence of poorly controlled encephalopathy correlated with a higher overall adverse event rate (P = .003). Sub-analysis revealed that patients without primary sclerosing cholangitis had a significantly higher overall rate of adverse events, pancreatitis, bleeding, and cardiopulmonary adverse events after ERCP when compared with those with primary sclerosing cholangitis. CONCLUSIONS: Our study was performed on a large series of patients with cirrhosis undergoing ERCP. Overall, the adverse events seen in patients with cirrhosis are similar to those seen in the general population of patients undergoing ERCP, although patients with CP classes B and C have higher adverse event rates compared with those with CP class A. Patients with cirrhosis without primary sclerosing cholangitis had significantly greater adverse event rates when compared with patients with primary sclerosing cholangitis.

Endoscopic ultrasound-fine needle injection for oncological therapy.

The minimal invasiveness and precision of endoscopic ultrasound (EUS) has lead to both its widespread use as a diagnostic and staging modality for gastrointestinal and pancreaticobiliary malignancies, and to its expanding role as a therapeutic modality. EUS-guided celiac plexus neurolysis is now a well-accepted modality for palliation of pain in patients with pancreatic cancer. EUS-guided ablation, brachytherapy, fiducial marker placement, and antitumor agent injection have been described as methods of performing minimally invasive oncological therapy. EUS-fine needle injection may be performed as adjunctive, alternative, or palliative treatment. This review summarizes the studies to date that have described these methods. A literature search using the PubMed/MEDLINE databases was performed. While most published studies to date are limited with disappointing outcomes, the concept of a role of EUS in oncological therapy seems promising.

A Trial of Rectal Indomethacin to Prevent Post-ERCP Pancreatitis in Patients with Suspected Type 3 Sphincter of Oddi Dysfunction.

BACKGROUND AND AIM: Recent data have suggested that rectal indomethacin can also reduce the incidence of post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP). The aim of this study was to determine whether prophylactic rectal indomethacin with PD stenting would reduce the incidence and severity of PEP compared to PD stenting alone in patients undergoing manometry for suspected SOD type 3. PATIENTS AND METHODS: A retrospective review of consecutive patients who underwent an ERCP with manometry for suspected SOD type 3 was performed. Patients were divided into two groups: (a) those who received a prophylactic PD stent (n = 285) and (b) those who received a prophylactic PD stent and a single dose of 100-mg indomethacin suppositories after ERCP (n = 57). The rate of PEP was compared between the two groups. RESULTS: The two patient groups were similar with regard to patient and procedure risk factors for PEP. Post-ERCP pancreatitis developed in 22 % patients. There was no significant difference in the incidence of PEP in the PD stent group compared to the PD stent and indomethacin group (23 vs. 18 %, respectively; p = 0.39). Moderate-to-severe pancreatitis developed in 21 (7 %) patients in the PD stent group compared to 5 (9 %) patients in the PD stent and indomethacin group (p = 0.78). Among patients with PEP, the median length of hospital stay was not significantly longer in the PD stent group compared to the PD stent and indomethacin group (6 vs. 4 days, respectively; p = 0.11). CONCLUSIONS: In patients with suspected SOD type 3, prophylactic rectally administered indomethacin with PD stenting was not observed to affect the incidence or severity of post-ERCP pancreatitis when compared to PD stenting alone.

Enteral stents for the management of malignant colorectal obstruction.

Colorectal cancer (CRC) is the 3rd most common cancer in the United States with more than 10000 new cases diagnosed annually. Approximately 20% of patients with CRC will have distant metastasis at time of diagnosis, making them poor candidates for primary surgical resection. Similarly, 8%-25% of patients with CRC will present with bowel obstruction and will require palliative therapy. Emergent surgical decompression has a high mortality and morbidity, and often leads to a colostomy which impairs the patient's quality of life. In the last decade, there has been an increasing use of colonic stents for palliative therapy to relieve malignant colonic obstruction. Colonic stents have been shown to be effective and safe to treat obstruction from CRC, and are now the therapy of choice in this scenario. In the setting of an acute bowel obstruction in patients with potentially resectable colon cancer, stents may be used to delay surgery and thus allow for decompression, adequate bowel preparation, and optimization of the patient's condition for curative surgical intervention. An overall complication rate (major and minor) of up to 25% has been associated with the procedure. Long term failure of stents may result from stent migration and tumor ingrowth. In the majority of cases, repeat stenting or surgical intervention can successfully overcome these adverse effects.

Exposing medical students to child and adolescent psychiatry: a case-based seminar.

OBJECTIVE: Despite a documented shortage of child and adolescent psychiatrists, few studies have examined whether including child and adolescent psychiatry didactics in a medical school curriculum can stimulate appreciation and interest among students, possibly leading more students to choose careers in this specialty. METHODS: The authors surveyed third-year medical students at the Feinberg School of Medicine of Northwestern University regarding their reactions to a 3-hour case-based seminar on child and adolescent psychiatry topics recently implemented as part of the general psychiatry clerkship. RESULTS: Student ratings reflected a positive view of the field and many students reported an increased likelihood of considering the specialty as a career after the seminar. In addition, students desired increased exposure to child and adolescent psychiatry while in medical school. CONCLUSION: Medical schools may consider providing students with increased exposure to child and adolescent psychiatry as this may encourage more future physicians to enter the field.