Serial lipase measurements in pancreatic panniculitis.

Pancreatic panniculitis is a rare cutaneous manifestation of pancreatic disease with only scant case reports available to guide management. In this report, a woman in her 60s developed a painful, erythematous and indurated, nodular rash after an episode of acute pancreatitis postendoscopic retrograde cholangiopancreatography (ERCP). While clinically and radiologically the pancreatitis improved with standard conservative management, the panniculitis remained severely debilitating. Repeat testing of serum pancreatic enzymes revealed persistent and marked elevation. Octreotide was started to inhibit pancreatic enzyme release, and the lesions improved, with resolution of the panniculitis correlating with falling serum pancreatic enzyme levels. Hence, serial pancreatic enzyme testing may have utility in monitoring and management of pancreatic panniculitis.

Adverse childhood experiences in children and adolescents with sickle cell disease: A retrospective cohort study.

BACKGROUND: Adverse childhood experiences (ACEs) are linked to poor health outcomes; however, the relationship between ACEs and health outcomes among children and adolescents with sickle cell disease (SCD) has limited documentation in the published literature. PROCEDURE: This retrospective cohort study involved 45 children and 30 adolescents. Participants were screened using the Center for Youth Wellness ACE Questionnaire. Parents completed the questionnaire for children. Adolescents provided self-report. ACEs were treated as continuous and categorical scales: 0-1 verus ≥2 original ACEs (individual and/or familial level); 0-1 versus ≥2 additional ACEs (community level); and 0-3 versus ≥4 expanded ACEs (original + additional). Pain and acute chest syndrome events were compared using Wilcoxon rank-sum tests, and correlated with cumulative ACE scores using Spearman's correlation. Multivariable models were fitted to examine the association between ACEs and pain/acute chest syndrome. RESULTS: The cumulative number of original ACEs positively correlated with acute chest syndrome events (rho = .53, p = .003) and pain (rho = .40, p = .028) among adolescents. Adolescents with ≥2 versus 0-1 original ACEs had a higher number of acute chest syndrome events (4.9 ± 2.6 vs. 1.6 ± 2.2, p = .002); however, this association was confounded by asthma. Acute chest syndrome events and hospitalizations for pain did not differ among child ACE groups. Emergency department (ED) pain visits were higher among children with ≥4 versus 0-3 expanded ACEs (1.6 ± 2.8 vs. 3.3 ± 3.2, p = .042), even after controlling for SCD genotype, asthma, disease-modifying treatment, and follow-up years (p = .027). CONCLUSION: ACEs are linked to increased morbidity among children and adolescents with SCD. Prospective studies are needed to further understand this relationship and test ACE-protective remedies.

Lymphatic Malformation Responsive to Sirolimus in Keratinocytic Epidermal Nevus Syndrome with KRAS Mutation: A Case and Brief Literature Discussion.

We present a rare case of KRAS keratinocytic epidermal nevus syndrome with lymphatic malformation, responsive to treatment with sirolimus, an mTOR inhibitor. A brief review of the current literature regarding sirolimus use in vascular malformations, lymphatic malformations, regional overgrowth syndromes, and RASopathies is discussed.

Timing and Success of Postoperative Voiding Trial After Colpocleisis With and Without Concomitant Midurethral Sling.

OBJECTIVE: The aim of this study was to compare failure rates of first voiding trial (VT) within 7 days and on postoperative day (POD) 1 after colpocleisis with versus without concomitant midurethral sling (MUS). Predictors of POD 1 VT failure were also examined. METHODS: This was a retrospective cohort study of women undergoing colpocleisis from January 2012 to October 2019 comparing VT outcomes with versus without MUS. Primary outcome was first VT failure within 7 days; outcomes of VTs performed on POD 1 were also assessed. Association between MUS and VT failure and predictors of POD 1 VT failure were assessed via logistic regression. RESULTS: Of 119 women, 45.4% had concomitant MUS. First VT was performed on mean POD 3.1 ± 2.2 in the MUS group versus POD 1.8 ± 1.8 in the no MUS group (P < 0.01). The MUS group was less likely to undergo POD 1 VT (50% vs 83%, P < 0.01). Failure of the first VT did not differ (22.2% with MUS vs 32.8% without MUS, P = 0.20); no association between VT failure and MUS was noted (adjusted odds ratio [aOR], 0.6; 95% confidence interval [CI], 0.18-2.1). There were 68.1% (81/119) of participants who underwent POD 1 VT, MUS was performed in 33.3% (27/81). The POD 1 failure did not differ between those with 33.3% versus 40.7% without MUS (P = 0.52). Midurethral sling was not associated with POD 1 VT failure (aOR, 0.93; 95% CI, 0.27-3.23). In women undergoing POD 1 VT, preoperative postvoid residual was associated with VT failure (aOR, 1.39; 95% CI, 1.01-1.92). CONCLUSIONS: In women undergoing colpocleisis, MUS was not associated with VT failure within 7 days or on POD 1. Increased preoperative postvoid residual was associated with POD 1 VT failure.

Non-toxic fragment of botulinum neurotoxin type A and monomethyl auristatin E conjugate for targeted therapy for neuroendocrine tumors.

Surgical resection is the only cure for neuroendocrine tumors (NETs). However, widespread metastases have already occured by the time of initial diagnosis in many cases making complete surgical removal impossible. We developed a recombinant heavy-chain receptor binding domain (rHCR) of botulinum neurotoxin type A that can specifically target synaptic vesicle 2 (SV2), a surface receptor abundantly expressed in multiple neuroendocrine tumors. Expression of neuroendocrine differentiation markers chromogranin A (CgA) and achaete-scute complex 1 (ASCL1) were signficantly reduced when treated with rHCR. rHCR conjugated to the antimitotic agent monomethyl auristatin E (MMAE) significantly suppressed proliferation of pancreatic carcinoid (BON) and medullary thyroid cancer cells (MZ) at concentrations of 500 and 300 nM respectively, while no growth suppression was observed in pulmonary fibroblasts and cortical neuron control cell lines. In vivo, rHCR-MMAE significantly reduced tumor volume in mouse xenografts with no observed adverse effects. These data suggest recombinant HCR (rHCR) of BoNT/A preferentially targets neuroendocrine cancer without the neurotoxicity of the full BoNT/A and that SV2 is a specific and promising target for delivering drugs to neuroendocrine tumors.

Assessing patients' preferences for gender, age, and experience of their urogynecologic provider.

INTRODUCTION AND HYPOTHESIS: Understanding patient preferences regarding provider characteristics is an under-explored area in urogynecology. This study aims to describe patient preferences for urogynecologic care, including provider gender, age, experience, and presence of medical trainees. METHODS: This was a multicenter, cross-sectional, survey-based study assessing patient preferences with a voluntary, self-administered, anonymous questionnaire prior to their first urogynecology consult. A 5-point Likert scale addressing provider gender, age, experience, and presence of trainees was used. Descriptive statistics summarized patient characteristics and provider preferences. Chi-squared (or Fisher's exact) test was used to test for associations. RESULTS: Six hundred fifteen women participated from eight sites including all geographic regions across the US; 70.8% identified as white with mean age of 58.5 ± 14.2 years. Urinary incontinence was the most commonly reported symptom (45.9%); 51.4% saw a female provider. The majority of patients saw a provider 45-60 years old (42.8%) with > 15 years' experience (60.9%). Sixty-five percent of patients preferred a female provider; 10% preferred a male provider. Sixteen percent preferred a provider < 45 years old, 36% preferred 45-60 years old, and 11% of patients preferred a provider > 60 years old. Most patients preferred a provider with 5-15 or > 15 years' experience (49% and 46%, respectively). Eleven percent preferred the presence of trainees while 24% preferred trainee absence. CONCLUSION: Patient preferences regarding urogynecologic providers included female gender and provider age 45-60 years old with > 5 years' experience. Further study is needed to identify qualitative components associated with these preferences.

Utility of the Surgical Apgar Score in Head and Neck Squamous Cell Carcinoma.

Objectives To recognize the utility of the surgical Apgar score (SAS) in a noncutaneous head and neck squamous cell carcinoma (HNSCC) population. Study Design Retrospective case series with chart review. Setting Academic tertiary medical center. Subjects and Methods Patients (n = 563) undergoing noncutaneous HNSCC resection between April 2012 and March 2015 were included. Demographics, medical history, intraoperative data, and postoperative hospital summaries were collected. SASs were calculated following the published schema. The primary outcome was 30-day postoperative morbidity. A 2-sample t test, analysis of variance, and χ2 (or Fisher exact) test were used for statistical comparisons. A multivariable logistic regression analysis was conducted to identify independent predictors of 30-day morbidity. Results Mean SAS was 6.2 ± 1.5. SAS groups did not differ in age, sex, or race. Sixty-five patients (11.6%) had a SAS between 0 and 4, with 40 incidences of morbidity (61.5%), while 31 (5.5%) patients with SAS from 9 to 10 had 3 morbidity occurrences (9.7%). Results show that 30-day postoperative morbidity is inversely related to increasing SAS ( P < .0001). Furthermore, lower SAS was associated with significantly increased operative time (SAS 0-4: 9.3 ± 2.6 hours vs SAS 9-10: 3.0 ± 1.1 hours) and lengths of stay (SAS 0-4: 10.0 ± 7.3 days vs SAS 9-10: 1.6 ± 1.0 days), P < .0001. SAS remained highly significant after adjusting for potential confounding variables in the multivariable analysis ( P < .0001). Conclusions An increasing SAS is associated with significantly lower rates of 30-day postoperative morbidities in a noncutaneous HNSCC patient population.

Utility of the Modified Surgical Apgar Score in a Head and Neck Cancer Population.

Objective The Surgical Apgar Score (SAS) is a validated postoperative complication prediction model. The purpose of this study was to investigate the utility of the SAS in a diverse head and neck cancer population and to compare it with a recently developed modified SAS (mSAS) that accounts for intraoperative transfusion. Study Design Case series with chart review. Setting Academic tertiary care medical center. Subjects and Methods This study comprised 713 patients undergoing surgery for head and neck cancer from April 2012 to March 2015. SAS values were calculated according to intraoperative data obtained from anesthesia records. The mSAS was computed by assigning an estimated blood loss score of zero for patients receiving intraoperative transfusions. Primary outcome was 30-day postoperative morbidity. Results Mean SAS and mSAS were 6.3 ± 1.5 and 6.2 ± 1.7, respectively. SAS and mSAS were significantly associated with 30-day postoperative morbidity, length of stay, operative time, American Society of Anesthesiologists status, race, and body mass index ( P < .05); however, no significant association was detected for age, sex, and smoking status. Multivariable analysis identified SAS and mSAS as independent predictors of postoperative morbidity, with the mSAS ( P = .03) being a more robust predictor than the SAS ( P = .15). Strong inverse relationships were demonstrated for the SAS and mSAS with length of stay and operative time ( P < .0001). Conclusion The SAS serves as a useful metric for risk stratification of patients with head and neck cancer. With the inclusion of intraoperative transfusion, the mSAS demonstrates superior utility in predicting those at risk for postoperative complications.

Increased pancreatic cancer survival with greater lymph node retrieval in the National Cancer Data Base.

BACKGROUND: We evaluated the role of lymph node (LN) retrieval in pancreatic adenocarcinoma (PA) patients undergoing pancreaticoduodenectomy (PD). METHODS: We utilized the National Cancer Data Base; Cox regression models and logistic regression models were used for statistical evaluation. RESULTS: We evaluated 26,792 patients with PA who underwent PD. The mean LN retrieved in LN(-) patients was 10.8 vs 14.4 for LN(+) patients (P < 0.0001). Greater LN retrieval is an independent predictor of a negative microscopic margin and decreased length of stay. The median survival of LN(-) patients exceeded that of LN(+) patients (24.5 vs 15.1 months, P < 0.0001). Increasing LN retrieval is a significant predictor of survival in all patients, and in LN(-) patients. The relationship of increased LN retrieval and enhanced survival is a nearly linear trend. CONCLUSIONS: Rather than demonstrating an inflection point that defines the extent of adequate lymphadenectomy, this dataset demonstrates an incremental relationship between LN retrieval and survival.

A dance intervention for cancer survivors and their partners (RHYTHM).

PURPOSE: The purpose of this study was to assess the feasibility, acceptability, and impact of a ballroom dance intervention on improving quality of life (QOL) and relationship outcomes in cancer survivors and their partners. METHODS: We conducted a pilot randomized controlled trial with two arms (Restoring Health in You (and Your Partner) through Movement, RHYTHM): (1) immediate dance intervention and (2) delayed intervention (wait-list control). The intervention consisted of 10 private weekly dance lessons and 2 practice parties over 12 weeks. Main outcomes were physical activity (Godin Leisure-Time Exercise Questionnaire), functional capacity (6 Minute Walk Test), QOL (SF-36), Couples' trust (Dyadic Trust Scale), and other dyadic outcomes. Exit interviews were completed by all participating couples. RESULTS: Thirty-one women survivors (68% breast cancer) and their partners participated. Survivors were 57.9 years old on average and 22.6% African American. Partners had similar characteristics. RHYTHM had significant positive effects on physical activity (p = 0.05), on the mental component of QOL (p = 0.04), on vitality (p = 0.03), and on the dyadic trust scale (p = 0.04). Couples expressed satisfaction with the intervention including appreciating the opportunity to spend time and exercise together. Survivors saw this light-intensity physical activity as easing them into becoming more physically active. CONCLUSIONS: Light intensity ballroom dancing has the potential to improve cancer survivors' QOL. Larger trials are needed to build strong support for this ubiquitous and acceptable activity. IMPLICATIONS FOR CANCER SURVIVORS: Ballroom dance may be an important tool for cancer survivors to return to a physically active life and improve QOL and other aspects of their intimate life.

Use of a novel statistical technique to examine the delivery of breast cancer follow-up care by different types of oncology providers.

RATIONALE, AIMS AND OBJECTIVES: Frequent follow-up is recommended for the more than 3 million breast cancer survivors living in the USA. Given the multidisciplinary nature of breast cancer treatment, follow-up may be provided by medical oncologists, radiation oncologists, surgeons and primary care providers. This creates the potential for significant redundancy as well as gaps in care. The objective was to examine patterns of breast cancer follow-up provided by different types of oncologists and develop a statistical means of quantifying visit distribution over time. METHODS: We identified stage I-III breast cancer patients who underwent breast conservation from 2000 to 2006 (n = 12 139) within the SEER-Medicare linked database. Provider type was defined using Medicare specialty provider codes and AMA Masterfile. The coefficient of variation (CV) for time between oncologist follow-up visits was calculated. Ordinal logistic regression assessed factors associated with CV. RESULTS: Substantial variation in CV was observed. Sixty-seven per cent of patients with low CV (high visit regularity) received follow-up from a single oncologist type, versus 8% with high CV (low visit regularity). The number of oncologist types participating in follow-up had the greatest association with high CV (odds ratio 7.4 [6.7-8.3] and 15.4 [13.6-17.6] for two and three oncologist types). CONCLUSIONS: Using a novel means of quantifying follow-up visit regularity, we determined that breast cancer patients with dispersed follow-up with more than one oncologist have more disordered care. The CV could be used in electronic medical records to identify cancer survivors with more disordered.

Factors associated with increased incidence of severe toxicities following yttrium-90 resin microspheres in the treatment of hepatic malignancies.

AIM: To further define variables associated with increased incidences of severe toxicities following administration of yttrium-90 ((90)Y) microspheres. METHODS: Fifty-eight patients undergoing 79 treatments were retrospectively assessed for development of clinical and laboratory toxicity incidence following (90)Y administration. Severe toxicity events were defined using Common Terminology Criteria for Adverse Events version 4.03 and defined as grade ≥ 3. Univariate logistic regression analyses were used to evaluate the effect of different factors on the incidence of severe toxicity events. Multicollinearity was assessed for all factors with P < 0.1 using Pearson correlation matrices. All factors not excluded due to multicollinearity were included in a multivariate logistic regression model for each measurement of severe toxicity. RESULTS: Severe (grade ≥ 3) toxicities occurred following 21.5% of the 79 treatments included in our analysis. The most common severe laboratory toxicities were severe alkaline phosphatase (17.7%), albumin (12.7%), and total bilirubin (10.1%) toxicities. Decreased pre-treatment albumin (OR = 26.2, P = 0.010) and increased pre-treatment international normalized ratio (INR) (OR = 17.7, P = 0.048) were associated with development of severe hepatic toxicity. Increased pre-treatment aspartate aminotransferase (AST; OR = 7.4, P = 0.025) and decreased pre-treatment hemoglobin (OR = 12.5, P = 0.025) were associated with severe albumin toxicity. Increasing pre-treatment model for end-stage liver disease (MELD) score (OR = 1.8, P = 0.033) was associated with severe total bilirubin toxicity. Colorectal adenocarcinoma histology was associated with severe alkaline phosphatase toxicity (OR = 5.4, P = 0.043). CONCLUSION: Clinicians should carefully consider pre-treatment albumin, INR, AST, hemoglobin, MELD, and colorectal histology when choosing appropriate candidates for (90)Y microsphere therapy.

Postoperative bowel function, symptoms, and habits in women after vaginal reconstructive surgery.

INTRODUCTION AND HYPOTHESIS: The objective was to characterize postoperative bowel symptoms in women undergoing vaginal prolapse reconstructive surgery randomized to preoperative bowel preparation vs a regular diet. METHODS: Subjects (N = 121) completed two bowel diaries: a 7-day bowel diary immediately before surgery and a 14-day diary postoperatively. Self-reported bowel diary data and symptoms included the time to first bowel movement (BM), daily number of BMs, Bristol Stool Form Scale score, pain, and urgency associated with BM, episodes of fecal incontinence, and use of laxatives. Antiemetic use was abstracted from medical records. Outcomes of groups were compared using Chi-squared/Fisher's exact test or Student's t test as appropriate. RESULTS: Mean time to first postoperative BM was similar in the bowel preparation (n = 60) and control groups (n = 61), 81.2 ± 28.9 vs 78.6 ± 28.2 h, p = 0.85. With the first BM, there were no significant differences between bowel preparation and control groups regarding pain (17.2 vs 27.9 %, p = 0.17), fecal urgency with defecation (56.9 vs 52.5 %, p = 0.63), fecal incontinence (14.0 vs 15.0 %, p = 0.88) and >1 use of laxatives (93.3 vs 96.7 % p = 0.44) respectively. Antiemetic use was similar in both groups (48.3 vs 55.7 % respectively, p = 0.42). CONCLUSIONS: There were no differences in the return of bowel function and other bowel symptoms postoperatively between the randomized groups. Lack of bowel preparation does not have an impact on the risk of painful defecation postoperatively. This information may be used to inform patients regarding expectations for bowel function after vaginal reconstructive surgery.

Frequent disruption of chromodomain helicase DNA-binding protein 8 (CHD8) and functionally associated chromatin regulators in prostate cancer.

Abnormal expression and function of chromatin regulators results in the altered chromatin structure seen in cancer. The chromatin regulator CTCF, its cofactor CHD8, and antagonistic paralogue BORIS have wide-ranging effects on gene regulation. Their concurrent expression and regulation was examined in benign, localized, and metastatic prostate cancer (PCa) arrays with extended follow-up using an automated quantitative imaging system, VECTRA. Epithelial staining was quantified and compared against a range of clinicopathologic variables. CHD8 expression was decreased in HGPIN, localized, and metastatic PCa compared to benign (P < .001). CHD8 promoter hypermethylation, assessed by Quantitative Pyrosequencing, occurred in over 45% of primary cancers in this population as well as the TGCA database. Treatment of cell lines with the demethylating agent 5-Aza-2'-deoxycytidine reinduced expression. An interesting dichotomy for CHD8 was observed within primary cancers, with higher nuclear protein expression associated with adverse clinical outcomes including extracapsular extension (P = .007), presence of metastases (P = .025) and worse PSA-recurrence free survival (P = .048). CHD8 outperformed Gleason score and predicted biochemical failure within intermediate grade prostate cancers. The BORIS/CTCF expression ratio increased in localized (P = .03) and metastatic PCa (P = .006) and was associated with higher Gleason score (P = .02), increased tumor volume (P = .02) and positive margins (P = .04). Per cell heterogeneity of expression revealed all protein expression to be more heterogeneous in cancerous tissue (both P < .001), especially high grade (P < .01). In the first detailed analysis in cancer, a marked loss of CHD8 expression and increased BORIS/CTCF ratio indicate frequent disruption of CTCF and its effector genes in PCa.

Why some patients are unhappy: part 1. Relationship of preoperative nasal deformity to number of operations and a history of abuse or neglect.

BACKGROUND: Trauma (neglect or abuse) can create body shame (different from body dissatisfaction), driving some patients to seek aesthetic surgery. We hypothesized that a trauma history would be related to the severity of the original deformity and the drive to undergo repeated operations. METHODS: Descriptive statistics were computed for 100 secondary rhinoplasty patients, 50 of whom originally had dorsal humps, 21 of whom had straight, functional noses, and 29 of whom had subjectively normal noses but underwent multiple rhinoplasties. This latter group fulfills criteria for body dysmorphic disorder. RESULTS: Compared with patients with hump noses, patients with normal primary noses were 2.9 times more likely to be demanding 2.5 times more likely to be depressed, had undergone 3.0 times more rhinoplasties and other aesthetic operations, and were 3.8 times more likely to have confirmed trauma histories. Patients who had undergone more than three operations were 92.7 percent women; 85 percent originally had straight noses and had undergone an average of 7.56 rhinoplasties and 5.78 aesthetic operations; 85.4 percent had histories of abuse or neglect. CONCLUSIONS: Secondary rhinoplasty patients with normal preoperative noses, who fulfill the criteria for body dysmorphic disorder, had significantly higher prevalences of depression, demanding conduct, previous rhinoplasties and other aesthetic operations, and confirmed trauma histories than patients who originally had dorsal deformities or straight noses with functional symptoms. To the authors' knowledge, this is the first report of such associations. A history of childhood trauma may impact adult patient behavior and therefore the surgical experience.

Why some patients are unhappy: part 2. Relationship of nasal shape and trauma history to surgical success.

BACKGROUND: A previous report indicated that secondary rhinoplasty patients with normal preoperative noses displayed significantly higher prevalences of depression, demanding behavior, previous aesthetic operations, and confirmed trauma (abuse/neglect) histories than patients who originally had dorsal deformities or straight noses with functional symptoms. The authors hypothesized that abuse or neglect might also influence patient satisfaction and suggest screening criteria. METHODS: One hundred secondary rhinoplasty patients stratified by their original nasal shapes were examined by bivariate analysis to determine the characteristics associated with surgical satisfaction. Mediation analysis established intervening factors between total surgery number and patients' perceived success. Random forests identified important patient attributes that predicted surgical success; logistic regression confirmed these effects. RESULTS: Satisfied patients originally had dorsal humps, three or fewer previous operations, were not demanding or depressed, were not looking for perfect noses, and had no trauma histories. Dissatisfied patients originally had subjectively normal noses, more than three operations, were depressed, had demanding personalities, and had trauma histories. Patients who had undergone the most operations were most likely to request more surgery and least likely to be satisfied. A trauma (abuse/neglect) history was the most significant mediator between patient satisfaction and number of operations and the most prominent factor driving surgery in patients with milder deformities. CONCLUSIONS: Potentially causative links exist between trauma (abuse/neglect), body image disorders, and obsessive plastic surgery. Body dysmorphic disorder may be a model of the disordered adaptation to abuse or neglect, a variant of posttraumatic stress disorder. Our satisfied and dissatisfied patients shared common characteristics and therefore may be identifiable preoperatively.

Impact of cardiac comorbidity on early outcomes after pancreatic resection.

BACKGROUND: In patients undergoing pancreatic resection (PR), identification of subgroups at increased risk for postoperative complications can allow focused interventions that may improve outcomes. STUDY DESIGN: Patients undergoing PR from 2005-2010 were selected from the American College of Surgeons National Surgical Quality Improvement Program database and categorized as having any history of cardiac disease (angina, congestive heart failure (CHF), myocardial infarction (MI), cardiac stent, or bypass) or as having acute cardiac disease (symptoms of CHF or angina within 30 days or MI within 6 months). These variables were utilized to examine the relationship between cardiac disease and outcomes after PR. RESULTS: The rate of serious complications and perioperative mortality in patients with any history of cardiac disease vs. those without was 34 vs. 24 % (p < 0.001) and 4.5 vs. 2.0 % (p < 0.001), respectively, and in patients with acute cardiac disease compared to patients without was 37 vs. 25 % (p < 0.001) and 8.6 vs. 2.2 % (p < 0.001), respectively. In multivariate analysis, the two cardiac disease variables remained associated with mortality. CONCLUSIONS: In patients undergoing PR, cardiac disease is a significant risk factor for adverse outcomes. These observations are critical for meaningful informed consent in patients considering pancreatectomy.

Development and multi-institutional validation of an upgrading risk tool for Gleason 6 prostate cancer.

BACKGROUND: Many patients with low-risk prostate cancer (PC) who are diagnosed with Gleason score 6 at biopsy are ultimately found to harbor higher grade PC (Gleason ≥ 7) at radical prostatectomy. This finding increases risk of recurrence and cancer-specific mortality. Validated clinical tools that are available preoperatively are needed to improve the ability to recognize likelihood of upgrading in patients with low-risk PC. METHODS: More than 30 clinicopathologic parameters were assessed in consecutive patients with Gleason 6 PC upon biopsy who underwent radical prostatectomy. A nomogram for predicting upgrading (Gleason ≥ 7) on final pathology was generated using multivariable logistic regression in a development cohort of 431 patients. External validation was performed in 2 separate cohorts consisting of 1151 patients and 392 patients. Nomogram performance was assessed using receiver operating characteristic curves, calibration, and decision analysis. RESULTS: On multivariable analysis, variables predicting upgrading were prostate-specific antigen density using ultrasound (odds ratio [OR] = 229, P = .003), obesity (OR = 1.90, P = .05), number of positive cores (OR = 1.23, P = .01), and maximum core involvement (OR = 0.02, P = .01). On internal validation, the bootstrap-corrected predictive accuracy was 0.753. External validation revealed a predictive accuracy of 0.677 and 0.672. The nomogram demonstrated excellent calibration in all 3 cohorts and decision curves demonstrated high net benefit across a wide range of threshold probabilities. The nomogram demonstrated areas under the curve of 0.597 to 0.672 for predicting upgrading in subsets of men with very low-risk PC who meet active surveillance criteria (all P < .001), allowing further risk stratification of these individuals. CONCLUSIONS: A nomogram was developed and externally validated that uses preoperative clinical parameters and biopsy findings to predict the risk of pathological upgrading in Gleason 6 patients. This can be used to further inform patients with lower risk PC who are considering treatment or active surveillance.