Lifetime Health and Economic Outcomes of Biparametric Magnetic Resonance Imaging as First-Line Screening for Prostate Cancer : A Decision Model Analysis.

BACKGROUND: Contemporary prostate cancer (PCa) screening uses first-line prostate-specific antigen (PSA) testing, possibly followed by multiparametric magnetic resonance imaging (mpMRI) for men with elevated PSA levels. First-line biparametric MRI (bpMRI) screening has been proposed as an alternative. OBJECTIVE: To evaluate the comparative effectiveness and cost-effectiveness of first-line bpMRI versus PSA-based screening. DESIGN: Decision analysis using a microsimulation model. DATA SOURCES: Surveillance, Epidemiology, and End Results database; randomized trials. TARGET POPULATION: U.S. men aged 55 years with no prior screening or PCa diagnosis. TIME HORIZON: Lifetime. PERSPECTIVE: U.S. health care system. INTERVENTION: Biennial screening to age 69 years using first-line PSA testing (test-positive threshold, 4 µg/L) with or without second-line mpMRI or first-line bpMRI (test-positive threshold, PI-RADS [Prostate Imaging Reporting and Data System] 3 to 5 or 4 to 5), followed by biopsy guided by MRI or MRI plus transrectal ultrasonography. OUTCOME MEASURES: Screening tests, biopsies, diagnoses, overdiagnoses, treatments, PCa deaths, quality-adjusted and unadjusted life-years saved, and costs. RESULTS OF BASE-CASE ANALYSIS: For 1000 men, first-line bpMRI versus first-line PSA testing prevented 2 to 3 PCa deaths and added 10 to 30 life-years (4 to 11 days per person) but increased the number of biopsies by 1506 to 4174 and the number of overdiagnoses by 38 to 124 depending on the biopsy imaging scheme. At conventional cost-effectiveness thresholds, first-line PSA testing with mpMRI followed by either biopsy approach for PI-RADS 4 to 5 produced the greatest net monetary benefits. RESULTS OF SENSITIVITY ANALYSIS: First-line PSA testing remained more cost-effective even if bpMRI was free, all men with low-risk PCa underwent surveillance, or screening was quadrennial. LIMITATION: Performance of first-line bpMRI was based on second-line mpMRI data. CONCLUSION: Decision analysis suggests that comparative effectiveness and cost-effectiveness of PCa screening are driven by false-positive results and overdiagnoses, favoring first-line PSA testing with mpMRI over first-line bpMRI. PRIMARY FUNDING SOURCE: National Cancer Institute.

The association of patient and disease characteristics with the overtreatment of low-risk prostate cancer from 2010 to 2016.

BACKGROUND: Although active surveillance is the preferred management for low-risk prostate cancer (PCa), some men remain at risk of overtreatment with definitive local therapy. We hypothesized that baseline characteristics may be associated with overtreatment and represent a potential source of health disparities. We therefore examined the associations of patient and disease characteristics with the surgical overtreatment of low-risk PCa. METHODS: We identified men aged 45-75 years with cT1 cN0 cM0 prostate adenocarcinoma with biopsy Gleason score 6 and PSA < 10 ng/ml from 2010-2016 in the National Cancer Database (NCDB) and who underwent radical prostatectomy (RP). We evaluated the associations of baseline characteristics with clinically insignificant PCa (iPCa) at RP (i.e., "overtreatment"), defined as organ-confined (i.e., pT2) Gleason 3 + 3 disease, using multivariable logistic regression. RESULTS: We identified 36,088 men with low-risk PCa who underwent RP. The unadjusted rate of iPCa decreased during the study period, from 54.7% in 2010 to 40.0% in 2016. In multivariable analyses adjusting for baseline characteristics, older age (OR 0.98, 95% CI 0.97-0.98), later year of diagnosis (OR 0.62, 95% CI 0.57-0.67 for 2016 vs. 2010), Black race (OR 0.85, 95% CI 0.79-0.91), treatment at an academic/research program (OR 0.82, 95% CI 0.73-0.91), higher PSA (OR 0.91, 95% CI 0.90-0.92), and higher number of positive biopsy cores (OR 0.87, 95% CI 0.86-0.88) were independently associated with a lower risk of overtreatment (iPCa) at RP. Conversely, a greater number of biopsy cores sampled (OR 1.01, 95% CI 1.01-1.02) was independently associated with an increased risk of overtreatment (iPCa) at RP. CONCLUSIONS: We observed an ~27% reduction in rates of overtreatment of men with low-risk PCa over the study period. Several patient, disease, and structural characteristics are associated with detection of iPCa at RP and can inform the management of men with low-risk PCa to reduce potential overtreatment.

Postoperative Opioid Prescribing via Rule-Based Guidelines Derived from In-Hospital Consumption: An Assessment of Efficacy Based on Postdischarge Opioid Use.

BACKGROUND: Many institutions have developed operation-specific guidelines for opioid prescribing. These guidelines rarely incorporate in-hospital opioid consumption, which is highly correlated with consumption. We compare outcomes of several patient-centered approaches to prescribing that are derived from in-hospital consumption, including several experimental, rule-based prescribing guidelines and our current institutional guideline. STUDY DESIGN: We performed a retrospective, cohort study of all adults undergoing surgery at a single-academic medical center. Several rule-based guidelines, derived from in-hospital consumption (quantity of opioids consumed within 24 hours of discharge), were used to specify the theoretical quantity of opioid prescribed on discharge. The efficacy of the experimental guidelines was compared with 3 references: an approximation of our institution's tailored prescribing guideline; prescribing all patients the typical quantity of opioids consumed for patients undergoing the same operation; and a representative rule-based, tiered framework. For each scenario, we calculated the penalized residual sum of squares (reflecting the composite deviation from actual patient consumption, with 15% penalty for overprescribing) and the proportion of opioids consumed relative to prescribed. RESULTS: A total of 1,048 patients met inclusion criteria. Mean (SD) and median (interquartile range [IQR]) quantity of opioids consumed within 24 hours of discharge were 11.2 (26.9) morphine milligram equivalents and 0 (0 to 15) morphine milligram equivalents. Median (IQR) postdischarge consumption was 16 (0 to 150) morphine milligram equivalents. Our institutional guideline and the previously validated rule-based guideline outperform alternate approaches, with median (IQR) differences in prescribed vs consumed opioids of 0 (-60 to 27.25) and 37.5 (-37.5 to 37.5), respectively, corresponding to penalized residual sum of squares of 39,817,602 and 38,336,895, respectively. CONCLUSIONS: Rather than relying on fixed quantities for defined operations, rule-based guidelines offer a simple yet effective method for tailoring opioid prescribing to in-hospital consumption.

The Association of a Peritoneal Interposition Flap With Lymphocele Formation After Pelvic Lymph Node Dissection During Robotic-assisted Laparoscopic Radical Prostatectomy: A Systematic Review and Meta-analysis.

OBJECTIVE: To conduct a systematic review and meta-analysis to evaluate the association of a peritoneal interposition flap (PIF) with lymphocele formation following robotic-assisted laparoscopic radical prostatectomy (RALP) with pelvic lymph node dissection. METHODS: We conducted a systematic search of MEDLINE, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials through August 30, 2023, to identify randomized and nonrandomized studies comparing RALP with pelvic lymph node dissection with and without PIF. A random effects meta-analysis was then performed to evaluate the associations of PIF with 90-day postoperative outcomes. RESULTS: Five randomized controlled trials (RCTs) and four observational studies, including a total of 2941 patients, were included. The use of PIF was associated with a reduced risk of 90-day symptomatic lymphocele formation after RALP when examining only RCTs (pooled odds ratios [OR] 0.44, 95% CI 0.28-0.69; I2 =3%) and both RCTs and observational studies (OR 0.35, 95% CI 0.22-0.56; I2 =17%). Similarly, use of PIF was associated with a reduced risk of 90-day any lymphocele formation (OR 0.40, 95% CI 0.28-0.56, I2 =39%). There were no statistically significant differences in postoperative complications between the two groups (OR 0.89; 95% CI 0.69-1.14; I2 =20%). CONCLUSION: Use of the PIF is associated with an approximately 50% reduced risk of symptomatic and any lymphocele formation within 90-days of surgery, and it is not associated with an increase in postoperative complications.

Decision regret up to 6 years after sleeve gastrectomy.

BACKGROUND: Sleeve gastrectomy (SG) is one of the most popular types of weight loss surgery today but is neither risk-free nor universally effective. We previously demonstrated that 5% of Roux-en-Y gastric bypass (RYGB) patients and up to 20% of gastric banding patients report overall regret 4 years after surgery. This study explores patients' attitudes toward their decision to have SG and decision regret rates up to 6 years postoperatively. METHODS: We surveyed 185 patients who were at least 6 months post-SG (response rate 30%). We used a modified version of the Decision Regret Scale developed by Brehaut et al. We converted responses to a 0-100 scale so that higher scores (> 50) reflect greater regret. We characterized patients who expressed having overall decision regret (score > 50) vs. those who did not (≤ 50). Demographic and preoperative clinical information was extracted from the online medical records. RESULTS: Of 185 SG patients, only 13 (7%) reported regret scores > 50 (i.e. high decision regret). Mean time from SG to survey completion was 41 months (range 6-76 months). Unadjusted comparisons between the two groups revealed that patients with high regret scores had lower mean weight loss (32.1% vs. 48.9% EBMIL), and reported less improvement in quality-of-life (QoL), such as physical health (46.2% vs. 93.5% "somewhat" or "significantly" improved). The two groups were similar in short-term complications, but those reporting overall regret were more likely to report GI complaints such as bloating (61.5% vs. 30.4%). Finally, patients with regret scores > 50 were more likely to be further out from SG (median time since surgery 61.8 vs. 41.1 months). CONCLUSION: In our study, very few patients reported regret (7%) up to 6 years postoperatively, in line with prior reports after RYGB. Those with regret reported poorer QoL.

Conditional survival following radical cystectomy for urothelial carcinoma of the bladder.

INTRODUCTION: Traditional surveillance protocols do not adequately account for the decreasing risk of mortality over time in aggressive malignancies, such as bladder cancer. Rather, the risk of death depends on both the baseline risk of mortality and the time survived since treatment. We therefore evaluated the conditional survival of patients diagnosed with urothelial carcinoma of the bladder (UCB) following radical cystectomy (RC). PATIENTS AND METHODS: We identified patients aged 18 to 75 with Charlson 0-1 and pTany pN0-3 cM0 UCB diagnosed from 2006 to 2015 in the National Cancer Database and treated with RC. The 2- and 5-year conditional overall survival (COS)-i.e., the probability of surviving an additional 2- or 5-years given a specified time survived since treatment-was estimated using the Kaplan-Meier method. Multivariable Cox regression models with landmark time analysis were used to evaluate the associations of baseline characteristics with OS over time. RESULTS: A total of 15,594 patients were included in the study. Median follow-up was 27.8 months. The 2- and 5-year COS for the overall cohort increased through 36 months follow-up and then plateaued. When stratified by pT and pN stage, the COS gain increased with higher pT and pN stage, demonstrating the greatest increase over time for patients with pTany N1-3 disease (5-year COS of 23% at baseline, 58% at 36-months, and 71% at 60-months). In multivariable Cox regression modeling, pT and pN stage were significantly associated with higher all-cause mortality at baseline (HR 3.27 for pT4, HR 2.57 for pT3 vs. ≤pT2; HR 2.26 for pN2-3, HR 1.77 for pN1 vs. pN0), but these associations were attenuated in magnitude with increasing landmark times of 36- and 60-months (HR 1.63 for pT4, HR 1.35 for pT3 vs. ≤pT2; HR 1.34 for pN2-3, HR 1.27 for pN1 vs. pN0). Our study is limited by the retrospective design and the lack of cancer-specific survival data. CONCLUSIONS: Risk of death after RC varies with time elapsed since treatment and disease stage. Accordingly, stage-specific COS may be used to improve prognostication and surveillance protocols.

Acupuncture Treatment for Breast Cancer-Related Lymphedema: A Randomized Pilot Study.

Background: Methods of conservative management for breast cancer-related lymphedema (BCRL) are burdensome in terms of time, cost, and convenience. In addition, many patients are not candidates for surgical treatment. Preliminary results have demonstrated possible beneficial effects of acupuncture for patients with BCRL. In this small pilot study, we examined the safety and feasibility of an acupuncture randomized control trial (RCT) in this patient cohort, utilizing a battery of standardized clinical and patient-centered outcome measures. Methods and Results: Patients with BCRL were randomized 2:1 to the acupuncture (n = 10) or the control (n = 4) group. Patients received acupuncture to the unaffected extremity biweekly for 6 weeks. Feasibility was defined as enrollment ≥80%, completion of ≥9 of 12 acupuncture sessions per person, and ≥75% completion of three of three measurement visits. To inform a future adequately powered RCT, we describe within-group changes in patient-centered outcomes, including circumferential measurements, bioimpedance spectroscopy, perometry, cytokine levels, and patient quality of life. Adverse events were systematically tracked. Fourteen patients completed the study. Of those who received acupuncture (n = 10), 8 completed all 12 acupuncture sessions, and 2 patients completed 11 sessions. Ninety-three percent of all participants completed all three measurement visits. There was no consistent improvement in arm volumes. Inflammatory marker levels had inconclusive fluctuations among both groups. All patients receiving acupuncture demonstrated an improvement in their functional quality-of-life score. No severe adverse events occurred. Conclusions: A randomized controlled study of acupuncture for BCRL is feasible. The acupuncture intervention is acceptable in this population, without safety concerns in a small sample and warrants further investigation.

A 4-Year Institutional Experience of Immediate Lymphatic Reconstruction.

BACKGROUND: Up to one in three patients may go on to develop breast cancer-related lymphedema (BCRL) after treatment. Immediate lymphatic reconstruction (ILR) has been shown in early studies to reduce the risk of BCRL, but long-term outcomes are limited because of its recent introduction and institutions' differing eligibility requirements. This study evaluated the incidence of BCRL in a cohort that underwent ILR over the long term. METHODS: A retrospective review of all patients referred for ILR at the authors' institution from September of 2016 through September of 2020 was performed. Patients with preoperative measurements, a minimum of 6 months of follow-up data, and at least one completed lymphovenous bypass were identified. Medical records were reviewed for demographics, cancer treatment data, intraoperative management, and lymphedema incidence. RESULTS: A total of 186 patients with unilateral node-positive breast cancer underwent axillary nodal surgery and an attempt at ILR over the study period. Ninety patients underwent successful ILR and met all eligibility criteria, with a mean patient age of 54 ± 12.1 years and median body mass index of 26.6 kg/m 2 [interquartile range (IQR), 24.0 to 30.7 kg/m 2 ]. The median number of lymph nodes removed was 14 (IQR, eight to 19). Median follow-up was 17 months (range, 6 to 49 months). Eighty-seven percent of patients underwent adjuvant radiotherapy, and among them, 97% received regional lymph node irradiation. The overall rate of lymphedema was 9% at the end of the study period. CONCLUSIONS: With the use of strict follow-up guidelines over the long term, the authors' findings support that ILR at the time of axillary lymph node dissection is an effective procedure that reduces the risk of BCRL in a high-risk patient population. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Impact of National Accreditation Program for Rectal Cancer guidelines on surgical margin status.

BACKGROUND: The American College of Surgeons established the National Accreditation Program for Rectal Cancer (NAPRC) to standardize rectal cancer care. We sought to assess the impact of NAPRC guidelines at a tertiary care center on surgical margin status. MATERIALS AND METHODS: The Institutional NSQIP database was queried for patients with rectal adenocarcinoma undergoing surgery for curative intent two years prior to and following implementation of NAPRC guidelines. Primary outcome was surgical margin status before (pre-NAPRC) versus after (post-NAPRC) implementation of NAPRC guidelines. RESULTS: Surgical pathology in five (5%) pre-NAPRC and seven (8%) post-NAPRC patients had positive radial margins (p = 0.59); distal margins were positive in three (3%) post-NAPRC and six (7%) post-NAPRC patients (p = 0.37). Local recurrence was observed in seven (6%) pre-NAPRC patients, there were no recurrences to date in post-NAPRC patients (p = 0.15). Metastasis was observed in 18 (17%) pre-NAPRC patients and four (4%) post-NAPRC patients (p = 0.55). CONCLUSION: NAPRC implementation was not associated with a change in surgical margin status for rectal cancer at our institution. However, the NAPRC guidelines formalize evidence-based rectal cancer care and we anticipate that improvements will be greatest in low-volume hospitals which may not utilize multidisciplinary collaboration.

Variable Anatomy of the Lateral Upper Arm Lymphatic Channel: An Anatomical Risk Factor for Breast Cancer-Related Lymphedema.

BACKGROUND: The lateral upper arm channel is an accessory lymphatic pathway that drains the upper extremity by means of the deltopectoral groove and supraclavicular nodes, thereby bypassing the axilla. Its variable connectivity to the forearm has not been studied in vivo. METHODS: Indocyanine green (ICG) lymphography was performed preoperatively to map the superficial and functional arm lymphatics in breast cancer patients without clinical or objective evidence of lymphedema. A retrospective review was performed to extract demographic, ICG imaging, and surgical data. RESULTS: Sixty patients underwent ICG lymphography before axillary lymph node dissection between June of 2019 and October of 2020. In 59%, the lateral upper arm lymphatic channel was contiguous with the forearm (long bundle). In 38%, the lateral upper arm lymphatic channel was present but not contiguous with the forearm (short bundle). In 3%, the lateral upper arm pathway was entirely absent. Seven patients developed at least one sign of lymphedema during postoperative surveillance, of which 71% demonstrated the short bundle variant. CONCLUSION: Although the lateral upper arm pathway is most often present, its connections to the forearm are frequently absent (short bundle), which, in this pilot report, appears to represent a potential risk factor for the development of lymphedema. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, V.

Disparities in the prevalence and management of high-risk non-muscle invasive bladder cancer.

OBJECTIVE: To evaluate the associations of socioeconomic characteristics with the management of non-muscle invasive bladder cancer (NMIBC). METHODS: We identified adult patients aged 18 to 89 years with Ta, T1, or Tis NMIBC in the NCDB. We then examined the associations of patient and socioeconomic characteristics with the guidelines-based management of high-risk NMIBC using multivariable logistic regression. RESULTS: 163,949 patients were included in the study cohort, including 64% with Ta, 32% with T1, and 4% with Tis disease. Among those diagnosed with bladder cancer, male (OR 1.24, 95%CI 1.21-1.27), uninsured (OR 1.10, 95%CI 1.01-1.19 vs. private), and non-White (OR 1.34, 95%CI 1.28-1.41 for Black; OR 1.10; 95%CI 1.03-1.18 for Other vs. White) patients were more likely to be diagnosed with high-risk disease, as well as patients from lower education level areas. Among those with high-risk NMIBC, patients who were older, non-White, Hispanic, uninsured or insured with Medicaid were less likely to receive guideline recommended intravesical BCG, while those residing in rural and higher education level areas were more likely to receive BCG. When examining non-guidelines based use of radiotherapy for HGT1 disease, older age (OR 1.06; 95% CI 1.04-1.07) and VA/Military insurance (OR 2.73; 95%CI 1.07, 6.98 vs. private) were associated with radiotherapy use. CONCLUSION: There are strong disparities in the prevalence and management of high-risk NMIBC. These observations highlight important targets for future strategies to reduce such healthcare disparities and provide more equitable bladder cancer treatment to patients.

Urothelial carcinoma of the bladder with isolated lymph node metastasis: Natural history and outcomes following surgical resection.

INTRODUCTION: Although pathologic lymph node involvement carries a poor prognosis in patients with urothelial carcinoma of the bladder (UCB), a subset of patients may demonstrate durable survival following surgical resection. To this end, there are limited contemporary data describing the natural history of UCB in patients with isolated lymph node involvement (cN0pN+) following radical cystectomy (RC) with pelvic lymph node dissection (PLND). We therefore utilized a large, nationwide oncology dataset to examine the natural history and outcomes of cN0 pN+ UCB after surgical resection. MATERIALS AND METHODS: We identified patients in the National Cancer Database (NCDB) with cN0 pN+ cM0 UCB from 2006 to 2015 treated with RC and PLND. The associations of baseline characteristics with all-cause mortality (ACM) were evaluated using Cox regression. RESULTS: A total of 2,884 patients formed the study cohort, including 42% with pN1 and 58% with pN2-3 disease. Of these, 606 (21%) received multiagent neoadjuvant chemotherapy, while 1,172 (41%) received postoperative adjuvant chemotherapy. A median of 15 (IQR 9-23) LNs were removed during PLND. The 5- and 7-year OS for the entire cohort were 20% and 17%, respectively. Compared to the overall cohort, patients surviving ≤5 years had lower pN stage (59% vs. 42% pN1) and lower pT stage (41% vs. 22% ≤pT2). On multivariable analysis, higher pT stage (HR 2.85, 95% CI 1.52-5.36 for pT3, HR 3.27, 95% CI 1.73-6.18 for pT4 vs. pT0), higher pN stage (HR 1.17, 95% CI 1.05-1.31 for pN2-3 vs. pN1), and increasing LN density (HR 2.37, 95% CI 1.88-2.99) were most strongly associated with increased ACM, while receipt of adjuvant chemotherapy (HR 0.61, 95% CI 0.55-0.68) was associated with reduced ACM. CONCLUSIONS: Although OS for patients with cN0 pN+ M0 UCB is poor, a subset of patients demonstrates durable long-term survival with 5- and 7-year OS of 20% and 17%, respectively. pT and pN stage represent important prognostic characteristics, while administration of adjuvant chemotherapy represents a potential therapeutic intervention associated with improved ACM.

Comparative Effectiveness of Magnetic Resonance Imaging-Ultrasound Fusion Versus In-bore Magnetic Resonance Imaging-targeted Prostate Biopsy.

OBJECTIVE: To examine the comparative effectiveness of magnetic resonance imaging-ultrasound (MRI-U/S) fusion biopsy and in-bore MRI-targeted biopsy. METHODS: We identified men aged 18-89 with a diagnosis of elevated prostate specific antigen (PSA) or Gleason 6 prostate cancer on active surveillance who underwent MRI-U/S fusion prostate biopsy (12-core + targeted) in the office or in-bore MRI-targeted biopsy (MRI-IB; targeted only). The cancer detection rate (CDR; Gleason 6-10) and clinically significant CDR (csCDR; Gleason 7-10) were compared across biopsy techniques, adjusted for patient and radiographic features. RESULTS: A total of 280 patients (346 lesions) were included, of whom 23.9% were on active surveillance for Gleason 6 prostate cancer. In the per-patient analyses, there was no statistically significant difference in adjusted overall CDR (64.1% vs 54.2%; P = .24) or csCDR (36.5% vs 37.9%; P = .85) between MRI-U/S and MRI-IB biopsy. In the per-lesion analyses, there was no statistically significant difference in adjusted overall CDR (45.7% vs 50.1%; P = .49) between MRI-U/S and MRI-IB biopsy, but MRI-IB biopsy was associated with a higher csCDR than MRI-U/S biopsy (32.8% vs 21.4%; P = .02). CONCLUSION: We observed no statistically significant differences in cancer detection rates between MRI-U/S fusion biopsy and MRI-IB biopsy in per-patient analyses. However, MRI-IB biopsy was associated with higher csCDR when considering targeted biopsy cores only. These results suggest that systematic cores should be obtained when performing MRI-U/S fusion biopsy.

Immunohistochemical analysis of Tn antigen expression in colorectal adenocarcinoma and precursor lesions.

BACKGROUND: The Tn antigen (CD175) is an O-glycan expressed in various types of human adenocarcinomas, including colorectal cancer (CRC), though prior studies have relied heavily upon poorly characterized in-house generated antibodies and lectins. In this study, we explored Tn expression in CRC using ReBaGs6, a well-characterized recombinant murine antibody with high specificity for clustered Tn antigen. METHODS: Using well-defined monoclonal antibodies, expression patterns of Tn and sialylated Tn (STn) antigens were characterized by immunostaining in CRC, in matched peritumoral [transitional margin (TM)] mucosa, and in normal colonic mucosa distant from the tumor, as well as in adenomas. Vicia villosa agglutinin lectin was used to detect terminal GalNAc expression. Histo-scoring (H scoring) of staining was carried out, and pairwise comparisons of staining levels between tissue types were performed using paired samples Wilcoxon rank sum tests, with statistical significance set at 0.05. RESULTS: While minimal intracellular Tn staining was seen in normal mucosa, significantly higher expression was observed in both TM mucosa (p < 0.001) and adenocarcinoma (p < 0.001). This pattern was reflected to a lesser degree by STn expression in these tissue types. Interestingly, TM mucosa demonstrates a Tn expression level even higher than that of the adenocarcinoma itself (p = 0.019). Colorectal adenomas demonstrated greater Tn and STn expression relative to normal mucosa (p < 0.001 and p = 0.012, respectively). CONCLUSIONS: In summary, CRC is characterized by alterations in Tn/STn antigen expression in neoplastic epithelium as well as peritumoral benign mucosa. Tn/STn antigens are seldom expressed in normal mucosa. This suggests that TM mucosa, in addition to CRC itself, represents a source of glycoproteins rich in Tn that may offer future biomarker targets.

Immediate radiotherapy versus observation in patients with node-positive prostate cancer after radical prostatectomy.

BACKGROUND: The optimal management of node-positive (pN1) prostate cancer following radical prostatectomy (RP) remains uncertain. Despite randomized evidence, utilization of immediate, life-long androgen deprivation therapy (ADT) remains poor, and recent trials of early salvage radiotherapy included only a minority of pN1 patients. We therefore emulated a hypothetical pragmatic trial of adjuvant radiotherapy versus observation in men with pN1 prostate cancer. METHODS: Using the RADICALS-RT trial to inform the design of a hypothetical trial, we identified men aged 50-69 years with pT2-3 Rany pN1 M0, pre-treatment PSA < 50 ng/mL prostate cancer in the NCDB from 2006 to 2015 treated with 60-72 Gy of adjuvant RT (aRT) ± ADT within 26 weeks of RP or observation. After estimating a propensity score for receipt of aRT, we estimated absolute and relative treatment effects using stabilized inverse probability of treatment (sIPW) re-weighting. RESULTS: In total, 3510 patients were included in the study, of whom 587 (17%) received aRT (73% with concurrent ADT). Median follow-up was 40.0 -months, during which 333 deaths occurred. After sIPW re-weighting, baseline characteristics were well-balanced. Adjusted overall survival (OS) was 93% versus 89% at 5-years and 82% versus 79% at 7-years for aRT versus observation (p = 0.11). In IPW-reweighted Cox regression, aRT was associated with a lower risk of all-cause mortality (ACM) than observation, but this did not reach statistical significance (HR 0.70 p = 0.06). In analyses examining heterogeneity of treatment effects, aRT was associated with improved ACM only for men with Gleason 8-10 disease (HR 0.59, p = 0.01), ≥2 positive LNs (HR 0.49, p = 0.04 for 2 positive LNs; HR 0.42, p = 0.01 for ≥3 positive LNs), or negative surgical margins (HR 0.50, p = 0.02). CONCLUSIONS: In observational analyses designed to emulate a hypothetical target trial of aRT versus observation in pN1 prostate cancer, aRT was associated with improved OS only for men with Gleason 8-10 disease, ≥2 positive LNs, or negative surgical margins.

Machine learning nonresponse adjustment of patient-reported opioid consumption data to enable consumption-informed postoperative opioid prescribing guidelines.

Background: Post-discharge opioid consumption is a crucial patient-reported outcome informing opioid prescribing guidelines, but its collection is resource-intensive and vulnerable to inaccuracy due to nonresponse bias. Methods: We developed a post-discharge text message-to-web survey system for efficient collection of patient-reported pain outcomes. We prospectively recruited surgical patients at Beth Israel Deaconess Medical Center in Boston, Massachusetts from March 2019 through October 2020, sending an SMS link to a secure web survey to quantify opioids consumed after discharge from hospitalization. Patient factors extracted from the electronic health record were tested for nonresponse bias and observable confounding. Following targeted learning-based nonresponse adjustment, procedure-specific opioid consumption quantiles (medians and 75th percentiles) were estimated and compared to a previous telephone-based reference survey. Results: 6553 patients were included. Opioid consumption was measured in 44% of patients (2868), including 21% (1342) through survey response. Characteristics associated with inability to measure opioid consumption included age, tobacco use, and prescribed opioid dose. Among the 10 most common procedures, median consumption was only 36% of the median prescription size; 64% of prescribed opioids were not consumed. Among those procedures, nonresponse adjustment corrected the median opioid consumption by an average of 37% (IQR: 7, 65%) compared to unadjusted estimates, and corrected the 75th percentile by an average of 5% (IQR: 0, 12%). This brought median estimates for 5/10 procedures closer to telephone survey-based consumption estimates, and 75th percentile estimates for 2/10 procedures closer to telephone survey-based estimates. Conclusions: SMS-recruited online surveying can generate reliable opioid consumption estimates after nonresponse adjustment using patient factors recorded in the electronic health record, protecting patients from the risk of inaccurate prescription guidelines.

Video Messaging to Increase Vascularized Composite Allograft Donation Willingness in United States Military Veterans.

Expansion of vascularized composite allograft (VCA) transplantation depends on the public's willingness to donate VCA organs, including face, extremities, and genitourinary organs. This study evaluated the effectiveness of video messaging on VCA donation willingness in US military veterans, a key stakeholder in VCA transplantation. Methods: Participants (n = 556) were randomized to 1 of 3 VCA video messaging interventions (informational, testimonial, or blended), a general (non-VCA) organ donation video message, or a control (nondonation) video message. Questionnaires were completed at pre- and postintervention and at 3-wk follow-up. Results: Veterans exposed to any VCA video messaging were more likely to express VCA donation willingness (69%, n = 203/296) than those exposed to general donation messaging (53%, n = 47 of 89; P = 0.006) or No Donation Messaging (37%, n = 36 of 97; P < 0.001). A significantly higher proportion of participants who received Blended VCA Messaging were willing to be VCA donors, compared with the Informational VCA Messaging group (79% versus 61%, P = 0.006). Each VCA messaging video resulted in a significant pre- to postintervention increase in the proportion of participants willing to donate their own face, hands, and legs (P < 0.03). Conclusions: Brief educational videos focused on VCA transplantation can have a demonstrable and verifiable impact on rates of VCA donation willingness in veterans.

Superficial and Functional Lymphatic Anatomy of the Upper Extremity.

BACKGROUND: Knowledge of detailed lymphatic anatomy in humans is limited, as the small size of lymphatic channels makes it difficult to image. Most current knowledge of the superficial lymphatic system has been obtained from cadaveric dissections. METHODS: Indocyanine green lymphography was performed preoperatively to map the functional arm lymphatics in breast cancer patients without clinical or objective evidence of lymphedema. A retrospective review was performed to extract demographic, indocyanine green imaging, and surgical data. RESULTS: Three main functional forearm channels with variable connections to two upper arm pathways were identified. The median forearm channel predominantly courses in the volar forearm (99 percent). The ulnar forearm channel courses in the volar forearm in the majority of patients (66 percent). The radial forearm channel courses in the dorsal forearm in the majority of patients (92 percent). Median (100 percent), radial (91 percent), and ulnar (96 percent) channels almost universally connect to the medial upper arm channel. In contrast, connections to the lateral upper arm channel occur less frequently from the radial (40 percent) and ulnar (31 percent) channels. CONCLUSIONS: This study details the anatomy of three forearm lymphatic channels and their connections to the upper arm in living adults without lymphatic disease. Knowledge of these pathways and variations is relevant to any individual performing procedures on the upper extremities, as injury to the superficial lymphatic system can predispose patients to the development of lymphedema.

Willingness of Kidney and Liver Transplant Candidates to Receive HCV-Infected Organs.

INTRODUCTION: Transplantation of organs exposed to hepatitis C virus (HCV) into uninfected patients has yielded excellent outcomes and more widespread adoption may lead to fewer discarded organs and more transplants. Patient perceptions may shed light on acceptability and likely the uptake of HCV+/HCV- transplantation, gaps in understanding, and perceived benefits/risks. METHODS: We surveyed 435 uninfected kidney and liver transplant candidates at four centers about their attitude towards HCV-infected organs. RESULTS: The percentage of patients willing to accept HCV-infected organs increased from 58% at baseline, to 86% following education about HCV, direct-acting antiviral agents (DAAs), and HCV+/HCV- transplantation benefits/risks. More willingness to accept an organ from an intravenous drug user (P < 0.001), age >50 y old (P = 0.02), longer waiting time (P = 0.02), more trust in the transplant system (P = 0.03), and previous awareness of DAAs (P = 0.04) were associated with higher willingness to accept an HCV-infected organ. The most important reasons for accepting an HCV-infected organ were a decrease in waiting time (65%), lower mortality and morbidity risk while on the waiting list (63%), effectiveness of DAAs (54%), and a quicker return to higher functional status (51%). CONCLUSIONS: Presenting patients with information about HCV+/HCV- transplantation in small doses that are calibrated to account for varying levels of health and numerical literacy is recommended.

Who doesn't fit? A multi-institutional study using machine learning to uncover the limits of opioid prescribing guidelines.

BACKGROUND: Many U.S. institutions have adopted postsurgical opioid-prescribing guidelines to standardize prescribing practices, and yet there is inherent variability in patients' opioid consumption after surgery. The utility of these guidelines is limited by the fact that some patients' needs will inevitably exceed them, and yet there are no evidence-based tools to help providers identify these patients. In this study we aimed to maximize the value of these guidelines by training machine learning models to predict patients whose needs will be met by these smaller recommended prescriptions, and patients who may require an additional degree of personalization. The aim of the present study was to develop predictive models for determining whether a surgical patient's postdischarge opioid requirement will fall above or below common opioid prescribing guidelines. METHODS: We conducted a retrospective cohort study of surgical patients at one institution from 2017 to 2018. Patients were called after discharge to collect opioid consumption data. Machine learning models were used to identify outlier opioid consumers (ie, exceeding our institutional prescribing guidelines) using diagnosis codes, medical history, in-hospital opioid use, and perioperative factors as predictors. External validation was performed on opioid consumption data collected at a second institution from 2020 to 2021, and sensitivity analysis was performed using a third institution's prescribing guidelines. RESULTS: The development and external validation cohorts included 1,867 and 498 patients, respectively. Age, body mass index, tobacco use, preoperative opioid exposure, and in-hospital opioid consumption were the strongest predictors of postdischarge consumption. A lasso regression model exhibited an area under the receiver operating characteristic curve of 0.74 (95% confidence interval 0.67-0.81) in predicting postdischarge opioid consumption. External validation of a limited lasso model yielded an area under the receiver operating characteristic curve of 0.67 (0.60-0.74). Performance was preserved when evaluated on another institution's guidelines (area under the receiver operating characteristic curve 0.76 [0.72-0.80]). CONCLUSION: Patient characteristics reliably predict postdischarge opioid consumption in relation to prescribing guidelines for both opioid-naive and exposed populations. This model may be used to help providers confidently follow prescribing guidelines for patients with typical opioid responsiveness and correctly pursue more personalized prescribing for others.