Metabolomic Characterization of Human Rectal Adenocarcinoma with Intact Tissue Magnetic Resonance Spectroscopy

PURPOSE: This study was designed to test whether metabolic characterization of intact, unaltered human rectal adenocarcinoma specimens is possible using the high-resolution magic angle spinning proton (1H) magnetic resonance spectroscopy technique. METHODS: The study included 23 specimens from five patients referred for ultrasonographic staging of suspected rectal cancer. Multiple biopsies of macroscopically malignant rectal tumors and benign rectal mucosa were obtained from each patient for a total of 14 malignant and 9 benign samples. Unaltered tissue samples were spectroscopically analyzed. Metabolic profiles were established from the spectroscopy data and correlated with histopathologic findings. RESULTS: Metabolomic profiles represented by principle components of metabolites measured from spectra differentiated between malignant and benign samples and correlated with the volume percent of cancer (P = 0.0065 and P = 0.02, respectively) and benign epithelium (P = 0.0051 and P = 0.0255, respectively), and with volume percent of stroma, and inflammation. CONCLUSIONS: Magnetic resonance spectroscopy of rectal biopsies has the ability to metabolically characterize samples and differentiate between pathological features of interest. Future studies should determine its utility in in vivo applications for non-invasive pathologic evaluations of suspicious rectal lesions

Longitudinal ECG changes in tetralogy of Fallot and association with surgical repair

BackgroundECG abnormalities have been linked to adverse changes in right ventricular (RV) morphology and poor clinical outcomes in repaired Tetralogy of Fallot (rTOF). Our aim was to describe how ECG changes progress in early and intermediate follow-up and whether types of surgical strategy at the time of primary repair affected these changes.MethodsWe studied patients with rTOF born 2000–2018 operated at our institution. Seven time points in relation to primary repair, follow-up, and pulmonary valve replacement (PVR) were identified. Patients correct with valve sparing repair (VSR), trans-annular patch (TAP) including with a monocusp valve (TAP + M) and with at least 3 ECGs were included. PQ interval, QRS duration, dispersion, and fragmentation, QTc duration and dispersion, JTc as well as presence of a right bundle branch block (RBBB) were analyzed. Medical records were reviewed for demographic and surgical data.ResultsTwo hundred nineteen patients with 882 ECGs were analyzed with a median follow-up time of 12.3 years (8.4, 17) with 41 (19%) needing PVR during the study period. QRS duration increased at time of primary repair to discharge from 66 msec (IQR 12) to 129 msec (IQR 27) (p < 0.0001) and at 1- and 6- year follow-up but showed only a modest and temporary decrease after PVR. QTc increased at the time of primary repair as well as prior to PVR. PQ interval showed a small increase at the time of primary repair, was at its highest prior to PVR and decreased with PVR. Type of surgical repair affected mainly QTc and JTc and was consistently longer in the TAP + M group until PVR. In VSR, QTc and JTc were prolonged initially compared to TAP but were similar after 1 year. After PVR, there were no differences in adverse ECG changes between surgical groups.ConclusionsPQ interval and QRS duration best correspond to the assumed volume load whereas the relationship with QTc and JTc is more complex, suggesting that these represent more complex remodeling of the myocardium. Before PVR, QTc and JTc are longer in the TAP + M group which may be due to a longer surgical incision

Anal incontinence and obstetric sphincter tears

PURPOSE: To evaluate the prevalence of anal incontinence (AI) in primiparous women five years after their first delivery; to investigate if an 8-12 hour time delay of primary repair affects AI at 1-year follow-up; to study the association between endoanal ultrasonography and anorectal manometry in relation to AI in primiparous women; to evaluate whether an endoanal ultrasonographic derived sphincter length-index correlates to subjective AI. METHODS: Primiparous women were prospectively followed with questionnaires before the pregnancy, at 5 and 9 months, and 5 years after the delivery. 242/349 women completed all questionnaires. Women with sphincter tear at their first delivery were compared to women without such injury. Risk factors for development of AI were analyzed. 165 women diagnosed with obstetrical sphincter tear at delivery were randomised to immediate or delayed (8-12 hour delay) repair. 78 were allocated to immediate operation and 87 to a delayed repair and followed for 12 months. A nested case-control study of 108/165 women from the randomized controlled trial was performed to compare findings at anorectal manometry and endoanal ultrasound 1 year after their repair. Cases were defined as having a greater score than 2 on the Pescatori incontinence scale, controls as having a score of 2 or less. 116 primiparous women who had experienced a 3rd or 4th degree obstetric tear were examined using three-dimensional endoanal ultrasonography and compared to a control group of nineteen nulliparous women to evaluate a sphincter length-index. RESULTS: AI increased significantly during the 5-year follow-up. Among women with sphincter tears, 44% reported AI at nine months and 53% at five years (p=0.002). Risk factors for AI at five years were age (OR 2.2, 95% CI 1.0; 4.6), sphincter tear (OR 2.3, 1.1; 5.0) and subsequent childbirth (OR 2.4, 1.1; 5.6). In the randomized study of delayed vs. immediate sphincter repair there was no significant difference in AI between the groups. Of the manometric variables, volume of first sensation and volume of first urge proved to be associated with AI at univariate statistical analysis. A distal scar in the external anal sphincter, age, degree of tear, and duration of second stage of labor were independently associated with AI. Patients with a previous grade 3-4 obstetric injury had a shorter external anal sphincter (p<0.001) and a lower IAS-index (p=0.03) than the controls. Patients with fecal urgency and flatus incontinence had a lower IAS-index (p=0.03 and 0.01 respectively). The EAS-index score was significantly lower in patients with fecal urgency (p=0.02). CONCLUSIONS: AI among primiparous women increase over time and is affected by further childbirth. There is no benefit or harm, with regards to anal continence at 1 year follow up, in delaying primary repair up to 12 hours after the delivery. Impaired rectal sensation at ano-rectal manometry and a distal scar at endoanal ultrasonography are associated with AI one year after primary sphincter repair in primiparous women. Measured by 3D endoanal ultrasound, the sphincter complex in nulliparous women is anatomically different when compared to women who have experienced primary repair after an obstetrical sphincter injury. An internal anal sphincter length index can be calculated based on ultrasonographic measurements and the IAS-index may correlate to the degree of AI

Serum depletion of complement component 5a is associated with increased inflammation and poor clinical outcomes in patients with perianal fistulas

Background: Persistent disease is a significant issue in the management of perianal fistulas, with up to 50% of patients representing following surgery and requiring additional treatment. Objective: The purpose of this study was to identify a novel prognostic modality in hopes of risk stratifying patients for persistent disease following corrective surgery. Design: This was a retrospective study based on prospectively collected data using a combination of histopathology, high throughput proteomic arrays, and ELISA based methods. Settings: This study used data on patients who underwent corrective surgery for perianal fistulas at the University of Illinois Hospital between June 2019 and July 2020. Patients: A cohort of 22 consecutive patients who corrective surgery for perianal fistulas was included in this study. The patients were divided into 2 groups: those with resolving fistulas (N = 13) and those with persisting fistulas (N = 9). Main outcome measures: Non-resolving fistulas were determined by disease re-presentation within 2 months of corrective surgery. Results: Serum samples from patients with persistent perianal fistulas displayed a consistent decrease in the expression of complement pathway component C5a compared to either healthy controls or patients with resolving forms of disease. This was paralleled by an increase in fistula expression of C5a and an associated increase in tissue infiltrating leukocytes and IL-1β expression. Limitations: The study was limited by its retrospective design, relatively small sample size, and single center data analysis. Conclusions: These results suggest that C5a is modestly depleted in patients with non-resolving forms of disease, and traffics to the site of tissue damage and inflammation. Accordingly, serum C5a warrants continued investigation as a prognostic biomarker and predictor of recurrence in patients presenting with perianal fistulas. See Video Abstract at http://links.lww.com/DCR/B982

No clinical benefit from routine histologic examination of stapler doughnuts at low anterior resection for rectal cancer

Background. The aim of this study was to evaluate the clinical utility and cost-effectiveness of routine histologic examination of the doughnuts from stapled anastomoses in patients undergoing a low anterior resection for rectal cancer. Methods. We performed a retrospective review of 486 patients who underwent a low anterior resection with stapled anastomosis for rectal cancer between 2002 and 2015 at 3 institutions. Pathologic findings in the doughnuts and their impact on patient management were recorded. Tumor characteristics that may influence how often doughnuts were included in the pathology report were analyzed. An approximate cost of histologic examination of doughnuts was also calculated. Results. A total of 412 patients (85 %) had doughnuts included in their pathology reports. Two patients had cancer cells in their doughnuts, and both patients had a positive distal margin in their primary tumor specimen; 33 patients had benign findings in their doughnuts. Pathologic examination of the doughnut did not change clinical management in any patient. Patients with rectosigmoid tumors were less likely to have their doughnuts included in the pathology report compared to patients with low tumors (P = .003). Doughnuts were not bundled with the primary tumor specimen in 374 (77 %) of our patients; in these patients, pathologic analysis of the doughnut added an additional cost of approximately $643 per specimen. Conclusion. This study demonstrates no clinical benefit in sending anastomotic doughnuts for histopathlogic evaluation after performing a low anterior resection with a stapled anastomosis for rectal cancer. Overall cost may be decreased if doughnuts are not analyzed or if they are bundled with the primary tumor specimen