Citations

Abstract Background Proctocolectomy with ileal pouch–anal anastomosis (IPAA) is the surgical procedure of choice for medically refractory ulcerative colitis and familial adenomatous polyposis. While rare, a pouch volvulus can occur. We aimed to determine the frequency, presentation, and management approach of pouch volvulus in patients with IPAA. Methods A systematic search of published literature was performed by a medical reference librarian on 10 August 2018 and two independent reviewers identified relevant publications, extracted data, and assessed the methodological quality based on a validated tool. A retrospective review of the Mayo Clinic electronic medical records identified one case of pouch volvulus between January 2008 and August 2018. Results The frequency of pouch volvulus from one large published study reporting long-term outcomes of IPAA was 0.18% (3/1,700). A total of 22 patients (18 ulcerative colitis) were included (median age 32 years, 73% females). Median time to volvulus after IPAA was 36 months while median interval to volvulus diagnosis from symptom onset was 24 hours. Abdominal pain was the most commonly reported symptom (76%). The diagnosis was made primarily by abdominal computed tomography (13/17 patients, 76%). Endoscopic treatment was successful in 1 of 11 patients (9%). Surgery was performed in 20 patients and pouch-pexy and pouch excision were the most frequent surgical operations. A redo IPAA was performed in five patients (25%). Conclusion Pouch volvulus is a rare but serious complication of IPAA and should be suspected even in the absence of obstruction symptoms. Endoscopic treatment often fails and surgery is effective when performed early.

Purpose. There are no known effective medical treatments for refractory MPNST. Inactivation of the NF1 tumor suppressor in MPNST results in upregulation of mTOR (mammalian target of rapamycin) signaling and angiogenesis, which contributes to disease progression. We conducted a phase II study for patients (pts) with refractory MPNST combining everolimus (10 mg PO once daily) with bevacizumab (10 mg/kg IV every 2 weeks) to determine the clinical benefit rate (CBR) (complete response, partial response (PR), or stable disease (SD) ≥ 4 months). Patients and Methods. Patients ≥18 years old with chemotherapy refractory sporadic or NF1 MPNST were eligible. Tumor response was assessed after every 2 cycles (the WHO criteria). A two-stage design targeting a 25% CBR was used: if ≥ 1/15 pts in stage 1 responded, enrollment would be expanded by 10 pts, and if ≥ 4/25 patients had clinical benefit, the combination would be considered active. Results. Twenty-five pts, 17 with NF1 and 8 with sporadic MPNST, enrolled. One of 15 pts in stage 1 had clinical benefit. Of 10 additional pts enrolled, 2 had clinical benefit. The median number of completed cycles was 3 (range 1–16). Adverse events were similar to those known for this combination. Conclusion. With a CBR of 12% (3/25), the combination of everolimus and bevacizumab did not reach the study’s target response rate and is not considered active in refractory MPNST.

AbstractBackgroundGlioblastoma (GBM) represents an aggressive cancer type with a median survival of only 14 months. With fewer than 5% of patients surviving 5 years, comprehensive profiling of these rare patients could elucidate prognostic biomarkers that may confer better patient outcomes. We utilized multiple molecular approaches to characterize the largest patient cohort of isocitrate dehydrogenase (IDH)–wildtype GBM long-term survivors (LTS) to date.MethodsRetrospective analysis was performed on 49 archived formalin-fixed paraffin embedded tumor specimens from patients diagnosed with GBM at the Mayo Clinic between December 1995 and September 2013. These patient samples were subdivided into 2 groups based on survival (12 LTS, 37 short-term survivors [STS]) and subsequently examined by mutation sequencing, copy number analysis, methylation profiling, and gene expression.ResultsOf the 49 patients analyzed in this study, LTS were younger at diagnosis (P = 0.016), more likely to be female (P = 0.048), and MGMT promoter methylated (UniD, P = 0.01). IDH-wildtype STS and LTS demonstrated classic GBM mutations and copy number changes. Pathway analysis of differentially expressed genes showed LTS enrichment for sphingomyelin metabolism, which has been linked to decreased GBM growth, invasion, and angiogenesis. STS were enriched for DNA repair and cell cycle control networks.ConclusionsWhile our findings largely report remarkable similarity between these LTS and more typical STS, unique attributes were observed in regard to altered gene expression and pathway enrichment. These attributes may be valuable prognostic markers and are worth further examination. Importantly, this study also underscores the limitations of existing biomarkers and classification methods in predicting patient prognosis.

Background Internal carotid artery (ICA) injury is a rare but potentially catastrophic complication of transsphenoidal resection (TSR) of pituitary tumors, potentially resulting in a host of deficits due to the risk of hemorrhage, ischemia, or even death. The endoscopic endonasal approach (EEA) has gained considerable popularity in the modern era, with few busy neurosurgeons remaining committed to practicing transnasal pituitary microsurgery. Our objective was therefore to characterize the overall incidence of ICA injury in a large, longitudinal, single-surgeon microscopic TSR series conducted during the modern EEA era. Methods Retrospective case series. Results Overall TSR volume by the senior author (F.B.M.) was 817 pituitary tumors during the study period, 2002 to 2017. Within that cohort, two instances of ICA injury were identified (0.2%), including one each with Cushing's disease and acromegaly, both of whom ultimately recovered without residual neurologic deficit. No pediatric injuries were identified. Conclusion Vascular injury is an exceedingly rare complication of transsphenoidal pituitary surgery. Adjuncts to prevent this complication include careful review of the coronal magnetic resonance imaging, identification of the midline, as needed use of the Doppler, and initial caudal opening of the sellar dura. Although potentially disastrous, good neurologic outcomes may be obtained, with immediate judicious packing followed by immediate digital subtraction angiography to assess vessel patency and secondary complications such as pseudoaneurysm.

Objectives: Data are lacking regarding implementation of novel strategies such as follow-up clinics and peer support groups, to reduce the burden of postintensive care syndrome. We sought to discover enablers that helped hospital-based clinicians establish post-ICU clinics and peer support programs, and identify barriers that challenged them. Design: Qualitative inquiry. The Consolidated Framework for Implementation Research was used to organize and analyze data. Setting: Two learning collaboratives (ICU follow-up clinics and peer support groups), representing 21 sites, across three continents. Subjects: Clinicians from 21 sites. Measurement and Main Results: Ten enablers and nine barriers to implementation of “ICU follow-up clinics” were described. A key enabler to generate support for clinics was providing insight into the human experience of survivorship, to obtain interest from hospital administrators. Significant barriers included patient and family lack of access to clinics and clinic funding. Nine enablers and five barriers to the implementation of “peer support groups” were identified. Key enablers included developing infrastructure to support successful operationalization of this complex intervention, flexibility about when peer support should be offered, belonging to the international learning collaborative. Significant barriers related to limited attendance by patients and families due to challenges in creating awareness, and uncertainty about who might be appropriate to attend and target in advertising. Conclusions: Several enablers and barriers to implementing ICU follow-up clinics and peer support groups should be taken into account and leveraged to improve ICU recovery. Among the most important enablers are motivated clinician leaders who persist to find a path forward despite obstacles.

3144 Background: Updated ASCO/CAP Guidelines for HER2 testing in breast cancer have been most impactful on the resolution of certain challenging groups of FISH results. We review the change in assignment of HER2 status in a large series of breast cancers referred to a large national reference laboratory for FISH testing since the introduction of the 2018 updated guidelines. Methods: Patient samples submitted to the Mayo Clinic Cytogenetics Laboratory (N = 2208) were analyzed by FISH. Samples with Group 2, Group 3, or Group 4 FISH results were reflexed to immunohistochemistry (IHC) in our central laboratory; FISH slides for those cases with equivocal 2+ IHC results were re-scored in the regions of invasive cancer showing more intense membranous staining. A subset of 202 samples with Group 4 FISH results were also reflexed to the previously employed reflex FISH assay (HER2/D17S122), and these were also re-analyzed according to the new reflex IHC/FISH process. Results: 382 of 2208 breast cancer samples tested (17.3%) had FISH results categorized as Group 2 (N = 17, 0.8%), Group 3 (N = 34, 1.5%), or Group 4 (N = 331, 15%) and required reflex IHC testing, and of those, 75% were 2+ equivocal and required targeted re-analysis of the FISH slide according to the 2018 updated guidelines. Re-analysis of the FISH slide resulted in switching between Groups 1-5 in 19.4% of cases, but HER2 status was changed by FISH re-scoring in only 7.7% of cases re-scored (1.0% of all samples), generally due to only minor shifts in HER2 copy number and HER2/control ratios between the initial and IHC-guided reflex FISH scores. In the subset of 202 cases tested by both reflex methods, the previously employed HER2/D17S122 reflex probe set was positive in 123 cases (60.9%), whereas reflex IHC/FISH was positive in only 10 cases (7.9%). Including positive reflex IHC (0.4%) and positive reflex FISH results (2.1%), the overall assignment of positive HER2 status on our series of 2208 cases was 11.5%. Conclusions: Overall rates of HER2 positive FISH results have declined under the most recent ASCO/CAP guideline update as a consequence of new recommendations for reflex testing for Groups 2-4. This change is largely due to reassignment of Group 2 and Group 4 results as negative in the absence of positive IHC.

Background Young age is a known factor associated with suboptimal adherence to endocrine therapy (ET) for adjuvant breast cancer (BC) treatment. This study was aimed at assessing nonadherent behaviors and associated factors among young women with early‐stage hormone receptor–positive BC. Methods As part of a multicenter, prospective cohort of women with a diagnosis of BC at or under the age of 40 years, participants were surveyed 30 months after their diagnosis about adherent behaviors. Among those who reported taking ET, adherence was measured with a 3‐item Likert‐type scale: Do you ever forget to take your ET? If you feel worse when you take your ET, do you stop taking it? Did you take your ET exactly as directed by your doctor over the last 3 months? Women reporting at least 1 nonadherent behavior were classified as nonadherers. Variables with a P value <.20 were included in a multivariable logistic model. Results Among 384 women, 194 (51%) were classified as nonadherers. Univariate factors that retained significance in the multivariable model included educational level (odds ratio [OR], 0.50 for high vs low; P = .04), level of social support according to the Medical Outcome Study Social Support Survey (OR, 0.98 per 1 point; P = .01), and confidence with the decision regarding ET measured on a 0 to 10 numerical scale (OR, 0.63 for high vs low; P = .04). Conclusions Findings from this study could help to identify young patients at higher risk for nonadherence. Interventions adapted to the level of education and aimed at reinforcing support and patients' confidence in their decision to take ET could improve adherence and associated outcomes in this population.