"What is the mechanism?": Cues, barriers, and opportunities to discuss foundational science during internal medicine rounds.

BACKGROUND: Repeated application of foundational science (FS) during medical reasoning results in encapsulation of knowledge needed to develop clinical expertise. Despite proven benefit of educating learners using a FS framework to anchor clinical decision making, how FS is integrated on clinical rotations has not been well characterized. This study examines how and when FS discussion occurs on internal medicine teaching rounds. MATERIAL AND METHODS: We performed a convergent mixed method study. Six internal medicine teams at a quaternary hospital were observed during rounds and team members interviewed. Transcripts were analyzed using thematic analysis. Descriptive statistics provided a summary of the observations. RESULTS: Our study revealed that rounds used a teacher-centered model where FS knowledge was transmitted as pearls external to the clinical context. FS content arose primarily when the patient was complex. Barriers preventing FS discussion were lack of time and perceived lack of personal FS knowledge. CONCLUSION: Our study describes scenarios that commonly elicit discussion of FS on inpatient medicine rounds highlighting a 'transmission' model of FS knowledge. We suggest a learner-centered model that engages students in the practice of integrating FS into clinical reasoning.

Image-Guided Percutaneous Ablation of Adrenal Metastases: A Meta-Analysis of Efficacy and Safety.

PURPOSE: To evaluate the efficacy and safety of percutaneous ablation of adrenal metastases through a meta-analysis of various image-guided percutaneous ablation techniques. MATERIALS AND METHODS: A comprehensive literature search of PubMed and Embase databases was performed for studies evaluating the efficacy and/or safety of image-guided percutaneous ablation of adrenal metastases. A total of 37 studies published between 2009 and 2020 were analyzed, comprising a sample size of 959 patients. Proportion estimates of overall survival, local control, and toxicity were analyzed in a pooled meta-analysis. The pooled prevalence of adverse events after ablation was calculated based on common terminology criteria for adverse events (CTCAE) grading. RESULTS: Of the 959 included patients, 320 (33.3%) underwent radiofrequency ablation, 72 (7.5%) microwave ablation, 95 (9.9%) cryoablation, and 46 (4.8%) ethanol injections for treatment of adrenal metastases. The remaining 426 (44.4%) patients were from studies involving a mixture of the 4 listed percutaneous ablation techniques. The pooled 1-year local control rate was 80% (95% confidence interval [CI], 76%-83%). The pooled 1-year overall survival rate was 77% (95% CI, 70%-83%). The overall rate of severe adverse events after ablation (CTCAE grade 3 or higher) was 16.1%. The overall rate of low-grade adverse events after ablation (CTCAE grade 2 or lower) was 32.6%. Approximately 21.9% (n = 203) of patients experienced intraprocedural hypertensive crises, the majority of which were reversed with antihypertensive medications. CONCLUSIONS: This study demonstrates that image-guided percutaneous ablation can be effective in achieving acceptable short- to mid-term local tumor control and overall survival with a moderate safety profile.

Factors Associated with Osteoid Osteoma Recurrence after CT-Guided Radiofrequency Ablation.

PURPOSE: To identify clinical and imaging variables associated with symptomatic recurrence of osteoid osteomas (OOs) treated with computerized tomography (CT)-guided radiofrequency (RF) ablation. MATERIALS AND METHODS: Seventy-one patients treated with the use of CT-guided RF ablation for OO at a single institution from July 2005 to May 2018 were included in this retrospective cohort analysis. Clinical data, including patient age, sex, race, and clinical outcomes, were collected from institutional electronic health records and telephone follow-up. Imaging variables regarding tumor characteristics were gathered from imaging reports and a blinded review of preprocedural images by an experienced musculoskeletal radiologist. Logistic regression, Cox proportional hazards, and Kaplan-Meier analyses were used to identify variables that are significantly associated with symptomatic recurrence, which was defined as pain occurring > 2 weeks after RF ablation. RESULTS: Ten patients (14.1%) experienced symptomatic recurrence at a median of 21.5 months after RF ablation. Univariable logistic regression classified young age (≤ 13 years), female sex, maximum tumor length, and "eccentricity index" (EI) ≥ 3 as predictive variables significantly associated with symptomatic recurrence. Multivariable logistic regression identified female sex and EI ≥ 3 to be significant predictors for symptomatic recurrence. A multivariable proportional hazards Cox regression of time to recurrence revealed EI ≥ 3 to be the only significant predictor of symptomatic recurrence. CONCLUSIONS: Female patients with OOs with an EI ≥ 3 have a greater risk of symptomatic recurrence following RF ablation. The EI is a useful tool to identify OOs with elongated 3-dimensional morphology, which may warrant more extensive ablation.

Phase 2 multi-institutional trial evaluating gemcitabine and stereotactic body radiotherapy for patients with locally advanced unresectable pancreatic adenocarcinoma.

BACKGROUND: This phase 2 multi-institutional study was designed to determine whether gemcitabine (GEM) with fractionated stereotactic body radiotherapy (SBRT) results in acceptable late grade 2 to 4 gastrointestinal toxicity when compared with a prior trial of GEM with single-fraction SBRT in patients with locally advanced pancreatic cancer (LAPC). METHODS: A total of 49 patients with LAPC received up to 3 doses of GEM (1000 mg/m(2)) followed by a 1-week break and SBRT (33.0 gray [Gy] in 5 fractions). After SBRT, patients continued to receive GEM until disease progression or toxicity. Toxicity was assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events [version 4.0] and the Radiation Therapy Oncology Group radiation morbidity scoring criteria. Patients completed the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (QLQ-C30) and pancreatic cancer-specific QLQ-PAN26 module before SBRT and at 4 weeks and 4 months after SBRT. RESULTS: The median follow-up was 13.9 months (range, 3.9-45.2 months). The median age of the patients was 67 years and 84% had tumors of the pancreatic head. Rates of acute and late (primary endpoint) grade ≥ 2 gastritis, fistula, enteritis, or ulcer toxicities were 2% and 11%, respectively. QLQ-C30 global quality of life scores remained stable from baseline to after SBRT (67 at baseline, median change of 0 at both follow-ups; P>.05 for both). Patients reported a significant improvement in pancreatic pain (P = .001) 4 weeks after SBRT on the QLQ-PAN26 questionnaire. The median plasma carbohydrate antigen 19-9 (CA 19-9) level was reduced after SBRT (median time after SBRT, 4.2 weeks; 220 U/mL vs 62 U/mL [P<.001]). The median overall survival was 13.9 months (95% confidence interval, 10.2 months-16.7 months). Freedom from local disease progression at 1 year was 78%. Four patients (8%) underwent margin-negative and lymph node-negative surgical resections. CONCLUSIONS: Fractionated SBRT with GEM results in minimal acute and late gastrointestinal toxicity. Future studies should incorporate SBRT with more aggressive multiagent chemotherapy.

The Prognostic Significance of Pretreatment Hematologic Parameters in Patients Undergoing Resection for Colorectal Cancer.

OBJECTIVES: The prognostic value of several hematologic parameters, including platelet, lymphocyte, and neutrophil counts, has been studied in a variety of solid tumors. In this study, we examined the significance of inflammatory markers and their prognostic implications in patients with colorectal cancer (CRC). MATERIALS AND METHODS: Patients with stage I-III CRC who underwent surgical resection at the Stanford Cancer Institute between 2005 and 2009 were included. Patients were excluded if they did not have preoperative complete blood counts performed within 1 month of surgical resection, underwent preoperative chemotherapy or radiation, had metastatic disease at diagnosis, or had another previous malignancy. We included 129 eligible patients with available preoperative complete blood counts in the final analysis. RESULTS: A preoperative neutrophil-to-lymphocyte ratio of>3.3 was significantly associated with worse disease-free (DFS) and overall survival (OS) (P=0.009, 0.003), as was a preoperative lymphocyte-to-monocyte ratio of ≤2.6 (P=0.01, 0.002). Preoperative lymphopenia (P=0.002) was associated with worse OS but not DFS (P=0.09). In addition, preoperative thrombocytosis was associated with worse DFS (P=0.006) and OS (P=0.010). Preoperative leukocytosis was associated with worse OS (P=0.048) but not DFS (P=0.49). Preoperative hemoglobin was neither associated with OS (P=0.24) or DFS (P=0.15). CONCLUSIONS: Pretreatment lymphopenia, thrombocytosis, a decreased lymphocyte-to-monocyte ratio, and an elevated neutrophil-to-lymphocyte ratio independently predict for worse OS in patients with CRC.

Statin and Metformin Use Prolongs Survival in Patients With Resectable Pancreatic Cancer.

OBJECTIVES: The aim of this study was to investigate the impact of statin and metformin therapy on disease outcome for patients with pancreatic ductal adenocarcinoma (PDAC). METHODS: This retrospective study included 171 PDAC patients who underwent surgical resection at the Stanford Cancer Institute between 1998 and 2013. No patients received neoadjuvant therapy. Statin and metformin use was defined as use during initial consult and continuing upon discharge from the hospital after surgery. Dose of each medication was recorded, as was the type of statin taken. RESULTS: The median follow-up for all patients was 11.23 months (range, 0.2-105.0 months). Among the 171 patients included in our analysis, 18 patients (10.5%) took metformin and 34 patients (19.9%) took statins. Statin use was associated with better overall survival (OS) in patients with PDAC (P = 0.011). Metformin use was also associated with better OS (P = 0.035). The use of statins remained significant on multivariate analysis for OS (P = 0.014; hazards ratio, 0.33; 95% confidence interval, 0.139-0.799), but metformin use did not (P = 0.33; hazards ratio 0.60, 95% confidence interval, 0.211-1.675). CONCLUSIONS: Statin and metformin use is associated with improved OS in patients with resectable PDAC. These medications should be further investigated for possible long-term use in the general population.

Patient-reported outcomes of a multicenter phase 2 study investigating gemcitabine and stereotactic body radiation therapy in locally advanced pancreatic cancer.

PURPOSE: We previously reported clinical outcomes and physician-reported toxicity of gemcitabine and hypofractionated stereotactic body radiation therapy (SBRT) in locally advanced pancreatic cancer (LAPC). Here we prospectively investigate the impact of gemcitabine and SBRT on patient-reported quality of life (QoL). METHODS AND MATERIALS: Forty-nine LAPC patients received 33 Gy SBRT (6.6 Gy daily fractions) upfront or after ≤3 doses of gemcitabine (1000 mg/m2) followed by gemcitabine until progression. European Organization for Research and Treatment of Cancer QoL core cancer (QLQ-C30) and pancreatic cancer-specific (European Organization for Research and Treatment of Cancer QLQ-PAN26) questionnaires were administered to patients pre-SBRT and at 4 to 6 weeks (first follow-up [1FUP]) and 4 months (2FUP) post-SBRT. Changes in QoL scores were deemed clinically relevant if median changes were at least 5 points in magnitude. RESULTS: Forty-three (88%) patients completed pre-SBRT questionnaires. Of these, 88% and 51% completed questionnaires at 1FUP and 2FUP, respectively. There was no change in global QoL from pre-SBRT to 1FUP (P = .17) or 2FUP (P > .99). Statistical and clinical improvements in pancreatic pain (P = .001) and body image (P = .007) were observed from pre-SBRT to 1FUP. Patients with 1FUP and 2FUP questionnaires reported statistically and clinically improved body image (P = .016) by 4 months. Although pancreatic pain initially demonstrated statistical and clinical improvement (P = .020), scores returned to enrollment levels by 2FUP (P = .486). A statistical and clinical decline in role functioning (P = .002) was observed in patients at 2FUP. CONCLUSIONS: Global QoL scores are not reduced with gemcitabine and SBRT. In this exploratory analysis, patients experience clinically relevant short-term improvements in pancreatic cancer-specific symptoms. Previously demonstrated acceptable clinical outcomes combined with these favorable QoL data indicate that SBRT can be easily integrated with other systemic therapies and may be a potential standard of care option in patients with LAPC.

Re-irradiation with stereotactic body radiation therapy as a novel treatment option for isolated local recurrence of pancreatic cancer after multimodality therapy: experience from two institutions.

Limited treatment options exist for isolated local recurrence of pancreatic ductal adenocarcinoma (PDA) following surgical resection accompanied by neoadjuvant or adjuvant chemoradiation therapy (CRT). While select patients are eligible for re-resection, recurrent lesions are often unresectable. Stereotactic body radiation therapy (SBRT) represents a possible minimally invasive treatment option for these patients, although published data in this setting are currently lacking. This study examines the safety, efficacy, and palliative capacity of re-irradiation with SBRT for isolated local PDA recurrence. All patients undergoing SBRT at two academic centers from 2008-2012 were retrospectively reviewed to identify those who received re-irradiation with SBRT for isolated local recurrence or progression of PDA after previous conventionally fractionated CRT. Information regarding demographics, clinicopathologic characteristics, therapies received, survival, symptom palliation, and toxicity was obtained from patient charts. Kaplan-Meier statistics were used to analyze survival and the log-rank test was used to compare survival among patient subgroups. Eighteen patients were identified. Fifteen had previously undergone resection with neoadjuvant or adjuvant CRT, while 3 received definitive CRT for locally advanced disease. Median CRT dose was 50.4 Gy [interquartile range (IQR), 45.0-50.4 Gy] in 28 fractions. All patients subsequently received gemcitabine-based maintenance chemotherapy, but developed isolated local disease recurrence or progression without evidence of distant metastasis. Locally recurrent or progressive disease was treated with SBRT to a median dose of 25.0 Gy (range, 20.0-27.0 Gy) in 5 fractions. Median survival from SBRT was 8.8 months (95% CI, 1.2-16.4 months). Despite having similar clinicopathologic disease characteristics, patients who experienced local progression greater than vs. less than 9 months after surgery/definitive CRT demonstrated superior median survival (11.3 vs. 3.4 months; P=0.019) and progression-free survival (10.6 vs. 3.2 months; P=0.030) after SBRT. Rates of freedom from local progression at 6 and 12 months after SBRT were 78% (14 of 18 patients) and 62% (5 of 8 patients), respectively. Effective symptom palliation was achieved in 4 of 7 patients (57%) who reported symptoms of abdominal or back pain prior to SBRT. Five patients (28%) experienced grade 2 acute toxicity; none experienced grade ≥3 acute toxicity. One patient (6%) experienced grade 3 late toxicity in the form of small bowel obstruction. In conclusion, re-irradiation with hypofractionated SBRT in this salvage scenario appears to be a safe and reasonable option for palliation of isolated local PDA recurrence or progression following previous conventional CRT. Patients with a progression-free interval of greater than 9 months prior to isolated local recurrence or progression may be most suitable for re-irradiation with SBRT, as they appear to have a better prognosis with survival that is long enough for local control to be of potential benefit.