Metastatic Neuroendocrine Neoplasms to the Pancreas: Two Unusual Cases and a Review of the Literature.

Neuroendocrine tumor metastases to the pancreas are rare, and they share substantial overlap with the significantly more common primary pancreatic neuroendocrine neoplasms, representing a potential diagnostic pitfall. Elucidating whether a neuroendocrine tumor within the pancreas is a primary neoplasm versus a metastasis has significant prognostic and treatment implications. Correlation with clinical history and imaging as well as incorporating an appropriate immunohistochemical panel are essential to establish the correct diagnosis. Herein, we present 2 rare neuroendocrine tumors that metastasized to the pancreas: a medullary thyroid carcinoma and an atypical carcinoid tumor of lung origin. We also provide a brief review of the literature.

Incidence and prevalence of advanced colorectal neoplasia in Lynch syndrome.

BACKGROUND AND AIMS: Lynch syndrome (LS) is the most common hereditary cause of colorectal cancer (CRC) and endometrial cancer (EC). Although colonoscopy reduces CRC in LS, the protection is variable. We assessed the prevalence and incidence of neoplasia in LS during surveillance colonoscopy in the United States and factors associated with advanced neoplasia. METHODS: Patients with LS undergoing ≥1 surveillance colonoscopy and with no personal history of invasive CRC or colorectal surgery were included. Prevalent and incident neoplasia was defined as occurring <6 months before and ≥6 months after germline diagnosis of LS, respectively. We assessed advanced adenoma (AA), CRC, and the impact of mismatch repair pathogenic variant (PV) and typical LS cancer history (personal history of EC and/or family history of EC/CRC) on outcome. RESULTS: A total of 132 patients (inclusive of 112 undergoing prevalent and incident surveillance) were included. The median examination interval and duration of prevalent and incident surveillance was .88 and 1.06 years and 3.1 and 4.6 years, respectively. Prevalent and incident AA were detected in 10.7% and 6.1% and invasive CRC in 0% and 2.3% of patients. All incident CRC occurred in MSH2 and MLH1 PV carriers and only 1 (.7%) while under surveillance in our center. AAs were detected in both LS cancer history cohorts and represented in all PVs. CONCLUSIONS: In a U.S. cohort of LS, advanced neoplasia rarely occurred over annual surveillance. CRC was diagnosed only in MSH2/MLH1 PV carriers. AAs occurred regardless of PV or LS cancer history. Prospective studies are warranted to confirm our findings.

Outcomes of Liver Transplantation in Patients With Preexisting Coronary Artery Disease.

BACKGROUND: Advances in surgical and medical technology over the years has made liver transplantation possible for older and higher risk patients. Despite rigorous preoperative cardiac testing, cardiovascular events remain a major cause of death after orthotopic liver transplantation (OLT). However, there are little data on the outcomes of OLT in patients with preexisting coronary artery disease (CAD). This study aimed to compare all-cause and cardiovascular mortality of patients with and without history of CAD undergoing OLT. METHODS: Six hundred ninety-three adult patients with cirrhosis underwent liver transplantation between July 2013 and December 2018 (female n = 243, male n = 450; median age 59). RESULTS: During the study period of 5 y (median follow-up, 24.1 mo), 92 of 693 patients (13.3%) died. All-cause mortality in the CAD group was significantly higher than in the non-CAD group (26.7% versus 9.6%; P <0.01). Cardiovascular events accounted for 52.5% of deaths (n = 21) in patients with CAD compared with 36.5% (n = 19) in non-CAD patients. At 6 mo, patients with combined nonalcoholic steatohepatitis (NASH)/CAD had significantly worse survival than those with CAD or NASH alone ( P <0.01). After 6 mo, patients with CAD alone had similar survival to those with combined NASH/CAD. CONCLUSIONS: Patients with preexisting CAD before liver transplantation are at higher risk of death from any cause, specifically cardiovascular-related death. This risk increases with coexisting NASH. The presence of NASH and CAD at the time of liver transplant should prompt the initiation of aggressive risk factor modification for patients with CAD.

Clinically actionable findings on surveillance EGD in asymptomatic patients with Lynch syndrome.

BACKGROUND AND AIMS: Lynch syndrome (LS) predisposes patients to multiple cancers including of the gastric and small bowel. Data supporting EGD surveillance in LS are limited. Our aim is to describe upper GI (UGI) findings in asymptomatic LS patients undergoing EGD surveillance within a hereditary colorectal cancer registry. METHODS: Asymptomatic patients with LS who underwent ≥1 surveillance EGD were included. Demographics, genotype, and EGD findings were reviewed. The frequency of clinically actionable findings including neoplasia (cancer, adenomas), Barrett's esophagus (BE), Helicobacter pylori, and hyperplastic polyps >5 mm were assessed. RESULTS: Three hundred twenty-three patients underwent 717 EGDs starting at a median age of 49.5 years. On average, each patient had 2 EGDs with an interval of 2.3 years between examinations. Clinically actionable findings were identified in 57 patients (17.6%). On baseline EGD 27.7% of findings were identified, with the remainder on surveillance EGD over an average of 3.5 years. Five asymptomatic patients (1.5%) had an UGI cancer detected during surveillance, all at early stage, including 1 patient each with BE-related esophageal adenocarcinoma, gastric neuroendocrine tumor, and gastric adenocarcinoma and 2 patients with duodenal adenocarcinoma. Two cancers were found on baseline EGD and 3 on follow-up EGD. CONCLUSIONS: Clinically actionable findings were found in approximately 1 in 6 asymptomatic patients with LS undergoing EGD surveillance. Five patients (1.5%) were diagnosed with cancer, all detected at an early stage. These data suggest that both baseline and follow-up EGD surveillance are effective in detecting early-stage UGI cancers in asymptomatic patients with LS.

The burden of cost in inflammatory bowel disease: a medical economic perspective.

PURPOSE OF REVIEW: The cost of care for inflammatory bowel disease (IBD) has nearly doubled over the last two decades. With evolving treatment paradigms utilizing costly but efficacious biologic agents earlier and more often, the cost burden is only expected to worsen. The purpose of this review is to explore the current economic landscape and drivers of IBD healthcare costs along with potential mechanisms for improving value and cost-effectiveness of IBD care. RECENT FINDINGS: The prevalence of IBD continues to rapidly expand with costs following suit. As compensation models change, the medical community is more incentivized than ever to develop cost reduction strategies including incorporation of high-value care measures, cooperative data aggregation, and technological solutions, with many of these interventions demonstrating promising results. SUMMARY: IBD is an expensive chronic disease with payments only expected to rise. In light of this financial conundrum, new practice models, such as the IBD specialty medical home and remote telemedicine, are being tested with an emphasis on cost reduction. Many of these strategies are demonstrating improved patient outcomes while also curbing expenses. These early successes set the stage for continued cooperation, collaboration, and growth in value-based management of IBD.

The Burden of Cost in Inflammatory Bowel Disease: A Medical Economic Perspective and the Future of Value-Based Care.

PURPOSE OF REVIEW: To examine the quantifiable economic impact of inflammatory bowel disease (IBD), key cost drivers and determinants, and the impact of value-based care in IBD. Finally, we prognosticate on future directions and opportunities on healthcare economics in IBD. RECENT FINDINGS: New value-based initiatives, technologically driven interventions, and quality improvement programs have demonstrated reductions in healthcare utilization and enhanced patient outcomes, and several have realized cost of care reductions. IBD is a costly, chronic illness with unbalanced spending by a small proportion of individuals. Pharmaceutical costs are overtaking inpatient expenses as the primary cost driver. Value-based care initiatives including the IBD medical home, remote monitoring platforms such as myIBDcoach and Project Sonar, and learning healthcare networks exemplified by ImproveCareNow have all demonstrated successes in improving care quality, patient outcomes, and reduced healthcare spending in some populations. The future of value-based care in IBD is bright, with ample opportunities for model refinement, collaboration, and growth.

Substituted cysteine scanning in D1-S6 of the sodium channel hNav1.4 alters kinetics and structural interactions of slow inactivation.

Slow inactivation in voltage-gated Na+ channels (Navs) plays an important physiological role in excitable tissues (muscle, heart, nerves) and mutations that disrupt Nav slow inactivation can result in pathophysiologies (myotonia, arrhythmias, epilepsy). While the molecular mechanisms responsible for slow inactivation remain elusive, previous studies have suggested a role for the pore-lining D1-S6 helix. The goals of this research were to determine if (1) cysteine substitutions in D1-S6 affect gating kinetics and (2) methanethiosulfonate ethylammonium (MTSEA) accessibility changes in different kinetic states. Site-directed mutagenesis in the human skeletal muscle isoform hNav1.4 was used to substitute cysteine for eleven amino acids in D1-S6 from L433 to L443. Mutants were expressed in HEK cells and recorded from with whole-cell patch clamp. All mutations affected one or more baseline kinetics of the sodium channel, including activation, fast inactivation, and slow inactivation. Substitution of cysteine (for nonpolar residues) adjacent to polar residues destabilized slow inactivation in G434C, F436C, I439C, and L441C. Cysteine substitution without adjacent polar residues enhanced slow inactivation in L438C and N440C, and disrupted possible H-bonds involving Y437:D4 S4-S5 and N440:D4-S6. MTSEA exposure in closed, fast-inactivated, or slow-inactivated states in most mutants had little-to-no effect. In I439C, MTSEA application in closed, fast-inactivated, and slow-inactivated states produced irreversible reduction in current, suggesting I439C accessibility to MTSEA in all three kinetic states. D1-S6 is important for Nav gating kinetics, stability of slow-inactivated state, structural contacts, and state-dependent positioning. However, prominent reconfiguration of D1-S6 may not occur in slow inactivation.

Systematic Review and Meta-analysis of Clinical Trials Examining the Benefit of Exercise Programmes Using Nordic Walking in Patients With Peripheral Artery Disease.

OBJECTIVES: An exercise programme is part of the initial management of peripheral artery disease (PAD). Nordic walking uses poles and a core-focused walking technique to reduce the load on the legs, which may have advantages as an exercise programme for PAD. This systematic review examined the benefit of a Nordic walking programme for treating PAD compared with other programmes. METHODS: A systematic approach was used to identify clinical trials comparing Nordic walking and control programmes in PAD patients. For inclusion, studies had to report maximum walking distance (MWD) measured with a treadmill test or corridor walking test both at entry and follow up. Study quality was appraised using the Cochrane collaboration tool for assessing risk of bias. An inverse variance weighted meta-analysis was performed to compare improvements in MWD. RESULTS: Five independent trials involving 294 patients were identified. In three trials, supervised Nordic walking programmes were compared with supervised standard walking. One trial compared a home based Nordic walking programme with a similar standard walking programme. One trial compared a partly supervised Nordic walking programme with best medical management. Meta-analysis of all data suggested that MWD improvements were similar for patients treated by Nordic and standard walking programmes (standardised mean difference, SMD = 1.31, 95% CI -1.28 to 3.91; p = .322). Findings for completely supervised programmes were similar to the primary analysis (SMD = -0.79, 95% CI -2.81 to 1.24; p = .446) while those from partially supervised or home based programmes favoured Nordic walking (SMD = 4.46, 95% CI 3.39, 5.53; p < .001), mainly due to results from one home based trial. CONCLUSIONS: This systematic review suggests no benefit of Nordic over standard walking as supervised exercise for PAD. Favourable results were reported for one home based Nordic walking programme. A larger trial is needed to assess whether this finding can be replicated or not.

A Randomized Controlled Trial to Compare e-Feedback Versus "Standard" Face-to-Face Verbal Feedback to Improve the Acquisition of Procedural Skill.

BACKGROUND: Constructive feedback plays an important role in learning during surgical training. Standard feedback is usually given verbally following direct observation of the procedure by a trained assessor. However, such feedback requires the physical presence of expert faculty members who are usually busy and time-constrained by clinical commitments. We aim to evaluate electronic feedback (e-feedback) after video observation of surgical suturing in comparison with standard face-to-face verbal feedback. METHODS: A prospective, blinded, randomized controlled trial comparing e-feedback with standard verbal feedback was carried out in February 2015 using a validated pro formas for assessment. The study participants were 38 undergraduate medical students from the University of Sheffield, UK. They were recorded on video performing the procedural skill, completed a self-evaluation form, and received e-feedback on the same day (group 1); observed directly by an assessor, invited to provide verbal self-reflection, and then received standard verbal feedback (group 2). In both groups, the feedback was provided after performing the procedure. The participants returned 2 days later and performed the same skill again. Poststudy questionnaire was used to assess the acceptability of each feedback among the participants. RESULTS: Overall, 19 students in group 1 and 18 students in group 2 completed the study. Although there was a significant improvement in the overall mean score on the second performance of the task for all participants (first performance mean 11.59, second performance mean 15.95; p ≤ 0.0001), there was no difference in the overall mean improvement score between group 1 and group 2 (4.74 and 3.94, respectively; p = 0.49). The mean overall scores for the e-feedback group at baseline recorded by 2 independent investigators showed good agreement (mean overall scores of 12.84 and 11.89; Cronbach α = 0.86). Poststudy questionnaire demonstrated that both e-feedback and standard verbal feedback achieved high mean Likert grades as recorded by the participants (4.42 [range: 2-5] and 4.71 [range: 4-5], respectively; p = 0.274). CONCLUSION: e-Feedback after watching a video recording appears to be acceptable and is not quantitatively different than standard feedback in improving suturing skills among novice trainees. Video assessment of procedural skills is reliable.

Assessing the Nontechnical Skills of Surgical Trainees: Views of the Theater Team.

OBJECTIVE: This study aims to explore the views of members of theater teams regarding the proposed introduction of a workplace-based assessment of nontechnical skills of surgeons (NOTSS) into the Intercollegiate Surgical Curriculum Programme in the United Kingdom. In addition, the previous training and familiarity of the members of the surgical theater team with the concept and assessment of NOTSS would be evaluated. DESIGN: A regional survey of members of theater teams (consultant surgeons, anesthetists, scrub nurses, and trainees) was performed at 1 teaching and 2 district general hospitals in South Yorkshire. RESULTS: There were 160 respondents corresponding to a response rate of 81%. The majority (77%) were not aware of the NOTSS assessment tool with only 9% of respondents reporting to have previously used the NOTSS tool and just 3% having received training in NOTSS assessment. Overall, 81% stated that assessing NOTSS was as important as assessing technical skills. Trainees attributed less importance to nontechnical skills than the other groups (p ≤ 0.016). Although opinion appears divided as to whether the presence of a consultant surgeon in theater could potentially make it difficult to assess a trainee's leadership skills and decision-making capabilities, overall 60% agree that the routine use of NOTSS assessment would enhance safety in the operating theater and 80% agree that the NOTSS tool should be introduced to assess the nontechnical skills of trainees in theater. However, a significantly lower proportion of trainees (45%) agreed on the latter compared with the other groups (p = 0.001). CONCLUSIONS: Our survey demonstrates acceptability among the theater team for the introduction of the NOTSS tool into the surgical curriculum. However, lack of familiarity highlights the importance of faculty training for assessors before such an introduction.

Long-term outcomes after stenting versus endarterectomy for treatment of symptomatic carotid stenosis: the International Carotid Stenting Study (ICSS) randomised trial.

BACKGROUND: Stenting is an alternative to endarterectomy for treatment of carotid artery stenosis, but long-term efficacy is uncertain. We report long-term data from the randomised International Carotid Stenting Study comparison of these treatments. METHODS: Patients with symptomatic carotid stenosis were randomly assigned 1:1 to open treatment with stenting or endarterectomy at 50 centres worldwide. Randomisation was computer generated centrally and allocated by telephone call or fax. Major outcomes were assessed by an independent endpoint committee unaware of treatment assignment. The primary endpoint was fatal or disabling stroke in any territory after randomisation to the end of follow-up. Analysis was by intention to treat ([ITT] all patients) and per protocol from 31 days after treatment (all patients in whom assigned treatment was completed). Functional ability was rated with the modified Rankin scale. This study is registered, number ISRCTN25337470. FINDINGS: 1713 patients were assigned to stenting (n=855) or endarterectomy (n=858) and followed up for a median of 4·2 years (IQR 3·0-5·2, maximum 10·0). Three patients withdrew immediately and, therefore, the ITT population comprised 1710 patients. The number of fatal or disabling strokes (52 vs 49) and cumulative 5-year risk did not differ significantly between the stenting and endarterectomy groups (6·4% vs 6·5%; hazard ratio [HR] 1·06, 95% CI 0·72-1·57, p=0·77). Any stroke was more frequent in the stenting group than in the endarterectomy group (119 vs 72 events; ITT population, 5-year cumulative risk 15·2% vs 9·4%, HR 1·71, 95% CI 1·28-2·30, p<0·001; per-protocol population, 5-year cumulative risk 8·9% vs 5·8%, 1·53, 1·02-2·31, p=0·04), but were mainly non-disabling strokes. The distribution of modified Rankin scale scores at 1 year, 5 years, or final follow-up did not differ significantly between treatment groups. INTERPRETATION: Long-term functional outcome and risk of fatal or disabling stroke are similar for stenting and endarterectomy for symptomatic carotid stenosis. FUNDING: Medical Research Council, Stroke Association, Sanofi-Synthélabo, European Union.

Carotid artery stenting: it's all about appropriate patient selection and keeping to the indications.

With increasing carotid artery stenting (CAS) expertise and improved CAS equipment, recent trials have demonstrated better results for CAS compared with earlier studies. As a result, it may be argued that CAS is currently non-inferior to carotid endarterectomy (CEA), at least in some patient subgroups. Consequently, there have been recent calls for extending CAS indications to include average surgical risk patients with symptomatic or asymptomatic carotid stenosis. However, CAS remains a less cost-effective option than CEA. Opening the floodgates to unrestricted CAS for both symptomatic and asymptomatic carotid patients would have considerable cost implications for any health system. Appropriate patient selection and keeping to the indications are crucial to optimize CAS outcomes.

Development of a modelled anatomical replica for training young neurosurgeons.

INTRODUCTION: The Modelled Anatomical Replica for Training Young Neurosurgeons (MARTYN) is a novel simulation model developed by the Royal College of Surgeons England (RCSEng). This study describes the development of the model and aims to determine its feasibility as a potential future training tool. METHODS AND MATERIALS: Traditional model-making methods were used to develop a prototype. Initial procedural trials tested the feasibility of the model. Eighteen participants, grouped by experience (nine novices, four intermediates and five experienced), completed two tasks: a craniotomy and a burr hole followed by insertion of an external ventricular drain (EVD). Subjective data on confidence, usefulness, realism and preference to other training modalities were collected via a standardised questionnaire and a 5-point Likert scale. RESULTS: Preliminary trials of the model prototype demonstrated feasibility. The novice group had the greatest self-reported benefit from MARTYN training, with significant increases in self-rated confidence in both the craniotomy (p < 0.01) and EVD insertion (p < 0.05) procedures. MARTYN was reported to having good visual and tactile realism overall with the bone component being considered highly realistic. The model was reported to be a useful training tool. When asked to rank preferred training modalities, operative experience was chosen first with cadaveric training and MARTYN consistently scoring a second choice. CONCLUSIONS: MARTYN was developed with the intention to fill the current niche for an inexpensive synthetic model head. This study shows that the use of MARTYN for training is both feasible and realistic. We demonstrate a preliminary face and construct validity of the model in this pilot study. With the reduction in working hours, we believe this model will be a suitable supplement to the current ST 1-3 level cadaveric training and will have a positive impact on patient safety.

Length of carotid stenosis predicts peri-procedural stroke or death and restenosis in patients randomized to endovascular treatment or endarterectomy.

BACKGROUND: The anatomy of carotid stenosis may influence the outcome of endovascular treatment or carotid endarterectomy. Whether anatomy favors one treatment over the other in terms of safety or efficacy has not been investigated in randomized trials. METHODS: In 414 patients with mostly symptomatic carotid stenosis randomized to endovascular treatment (angioplasty or stenting; n = 213) or carotid endarterectomy (n = 211) in the Carotid and Vertebral Artery Transluminal Angioplasty Study (CAVATAS), the degree and length of stenosis and plaque surface irregularity were assessed on baseline intraarterial angiography. Outcome measures were stroke or death occurring between randomization and 30 days after treatment, and ipsilateral stroke and restenosis ≥50% during follow-up. RESULTS: Carotid stenosis longer than 0.65 times the common carotid artery diameter was associated with increased risk of peri-procedural stroke or death after both endovascular treatment [odds ratio 2.79 (1.17-6.65), P = 0.02] and carotid endarterectomy [2.43 (1.03-5.73), P = 0.04], and with increased long-term risk of restenosis in endovascular treatment [hazard ratio 1.68 (1.12-2.53), P = 0.01]. The excess in restenosis after endovascular treatment compared with carotid endarterectomy was significantly greater in patients with long stenosis than with short stenosis at baseline (interaction P = 0.003). Results remained significant after multivariate adjustment. No associations were found for degree of stenosis and plaque surface. CONCLUSIONS: Increasing stenosis length is an independent risk factor for peri-procedural stroke or death in endovascular treatment and carotid endarterectomy, without favoring one treatment over the other. However, the excess restenosis rate after endovascular treatment compared with carotid endarterectomy increases with longer stenosis at baseline. Stenosis length merits further investigation in carotid revascularisation trials.

Workplace-based assessment in surgical training: experiences from the Intercollegiate Surgical Curriculum Programme.

BACKGROUND: The Intercollegiate Surgical Curriculum Programme was launched in the United Kingdom in 2007. At its heart was the reliance upon clear, defined curricula, competence-based training and the use of workplace-based assessments to assess the competence. The principle assessments used were Case-based Discussion, Procedure-based Assessments (PBA), Direct Observation of Procedural Skills, and Clinical Evaluation Exercise and a Multisource Feedback tool. METHODS: We report the initial experience with that system, and most importantly, the experience with workplace-based assessment. RESULTS: Themes include issues around faculty development, misuse of assessments, inappropriate timing of assessments, concerns about validity and reliability of the assessments and concerns about the actual process of workplace-based assessments. Of the assessments, the PBA performed best. CONCLUSIONS: As a consequence, there has been an increased focus upon faculty development, while some of the assessments have been redesigned in line with the PBA. A global rating scale has been introduced that uses clinical anchors. The rating scales have also been altered with a reduction in the number of ratings while an enhanced description of the complexity of the case has been introduced within the Case-based Discussion and the Clinical Evaluation Exercise. A re-evaluation will take place in the near future.

E-learning resources for vascular surgeons: a needs analysis study.

OBJECTIVES: To obtain the views of vascular surgeons about online resources in their specialty as a guide to future e-learning development. DESIGN: A focused questionnaire regarding e-learning resources in vascular surgery was circulated online. A combination of structured and open-ended questions addressed users' ranking of various resource types, examples of presently used websites, suggestions for future growth, and the opportunity to become actively involved in e-learning development. The responses were collected over a 4-week period and remained anonymous. SETTING: The study was conducted online at http://www.vasculareducation.com as part of an ongoing project on e-learning for vascular surgeons by the Department of Educational Development and Research, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, The Netherlands. PARTICIPANTS: The survey population consisted of vascular surgeons and surgical trainees in Europe. The participants were contacted via their membership of the European Society for Vascular Surgery and national academic or administrative vascular surgical organizations. Demographic information was collected about clinical seniority and country of work. RESULTS: In all, 252 responses were obtained. Respondents favored the development of a variety of online resources in vascular surgery. The strongest demand was for illustrations and videos of surgical techniques, followed by an interactive calendar and peer-reviewed multiple-choice questions. Overall, 46% of respondents wished to contribute actively toward e-learning development, with consultants being more willing than trainees to do so. CONCLUSIONS: Members of the vascular surgical community value online resources in their specialty, especially for procedural techniques. Vascular surgeons would like to be actively involved in subsequent development of e-learning resources.