High Opioid Prescribing Profiles Among Gastroenterologists: A Nationwide Analysis.

Chronic opioid use is associated with adverse effects on the gastrointestinal (GI) tract and increased morbidity.1-3 Despite efforts to de-escalate opioid use, 10% of outpatient GI visits are associated with an opioid prescription.4 Although we previously described declining opioid prescriptions to Medicare patients by most gastroenterologists,5 opioid prescriptions for GI conditions have increased.4 Considerable variation in opioid prescribing behavior exists in the general physician population, and a small percentage of high prescribers are responsible for driving opioid prescriptions.6,7 The aims of this study are (1) to examine the impact of high opioid prescribers (HPs) on overall prescription volume in gastroenterology and (2) identify characteristics associated with HPs.

Early-Onset Colorectal Cancer Is Associated with a Lower Risk of Metachronous Advanced Neoplasia than Traditional-Onset Colorectal Cancer.

BACKGROUND: Colorectal cancer (CRC) incidence in the USA has increased in adults under age 50. Current CRC surveillance guidelines do not consider age at diagnosis, and there are limited data available on outcomes from surveillance colonoscopies in early-onset CRC (EO-CRC) to guide recommendations on surveillance intervals. AIMS: To compare surveillance outcomes between EO-CRC and traditional-onset colorectal cancer (TO-CRC). METHODS: In a retrospective cohort study in a large tertiary care academic medical center, we collected data on patients with a diagnosis of CRC between 2000 and 2014 who received surgery with curative intent. We used log-rank test and inverse probability of treatment weighted Cox regression analysis to compare the development of metachronous advanced neoplasia (MAN) in patients with EO-CRC (diagnosed ages 18-49) and TO-CRC (diagnosed ages 50-75). RESULTS: Patients with EO-CRC (n = 107) were more likely to present with advanced-stage disease (62% versus 35%, p < 0.0001), rectal tumors (45% versus 27%, p < 0.01), and a family history of CRC (30% versus 16%, p = 0.02) compared to those with TO-CRC (n = 139). Patients with EO-CRC had lower risk of MAN (adjusted HR 0.44, 95% CI 0.22-0.88) than TO-CRC patients. The 5-year event rate for MAN was lower for patients with EO-CRC compared to patients with TO-CRC (5.8% vs. 16.1%, p = 0.07). The presence of synchronous neoplasia or history of diabetes was also predictive of MAN. CONCLUSIONS: EO-CRC was independently associated with a lower risk of developing MAN compared to TO-CRC. Shorter surveillance intervals may not be warranted in EO-CRC; however, large prospective studies are needed.

Increasing Rates of Opioid Prescriptions for Gastrointestinal Diseases in the United States.

INTRODUCTION: Pain control is an important management approach for many gastrointestinal conditions. Because of the ongoing opioid crisis, public health efforts have focused on limiting opioid prescriptions. This study examines national opioid prescribing patterns and factors associated with opioid prescriptions for gastrointestinal conditions. METHODS: We conducted a repeated cross-sectional study using the National Ambulatory Medical Care Survey data from 2006 to 2016. The International Classification of Diseases codes were used to identify ambulatory visits with a primary gastrointestinal diagnosis. Data were weighted to calculate national estimates for opioid prescriptions for gastrointestinal disease. Joinpoint regression was used to analyze temporal trends. Multivariable logistic regression was used to examine factors associated with opioid prescriptions. RESULTS: We analyzed 12,170 visits with a primary gastrointestinal diagnosis, representing 351 million visits. The opioid prescription rate for gastrointestinal visits was 10.1% (95% confidence interval [CI] 9.0%-11.2%). Opioid prescription rates for gastrointestinal disease increased by 0.5% per year from 2006 to 2016 (P = 0.04). Prescription rates were highest for chronic pancreatitis (25.1%) and chronic liver disease (13.9%) visits. Seventy-one percent of opioid prescriptions were continuations of an existing prescription. Patient characteristics associated with continued opioid prescriptions included rural location (adjusted odds ratio [aOR] 1.46; 95% CI 1.11-1.93), depression (aOR 1.83; 95% CI 1.33-2.53), and Medicaid insurance (aOR 1.57; 95% CI 1.15-2.13). DISCUSSION: Opioid prescription rates for gastrointestinal disease visits increased from 2006 to 2016. Our findings suggest an inadequate response to the opioid epidemic by providers managing gastrointestinal conditions. Further clinical interventions are needed to limit opioid use for gastrointestinal disease.(Equation is included in full-text article.).

Advanced-Stage Colorectal Cancer in Persons Younger Than 50 Years Not Associated With Longer Duration of Symptoms or Time to Diagnosis.

BACKGROUND & AIMS: The incidence of colorectal cancer (CRC) is increasing in the United States among adults younger than the age of 50 years. Studies of young-onset CRC have focused on outcomes and treatment patterns. We examined patient presentation, provider evaluation, and time to diagnosis, which can affect stage and prognosis. METHODS: In a retrospective study, we collected data from patients with a diagnosis of colorectal adenocarcinoma, confirmed by pathologists, seen at the Stanford Cancer Institute from January 1, 2008, through December 31, 2014. We compared symptoms, clinical features, time to diagnosis, and cancer stage in patients with young-onset CRC (diagnosed at an age younger than 50 years; n = 253) with patients diagnosed with CRC at an age of 50 years or older (n = 232). RESULTS: A higher proportion of patients with young-onset CRC were diagnosed with advanced-stage tumors (72%) compared with older patients (63%) (P = .03). Larger proportions of patients with young-onset CRC also had a family history of CRC (25% vs 17% in older patients; P = .03), confirmed or probable hereditary cancer syndromes (7% vs 1% in older patients; P < .01), and left-sided disease (distal colon cancer in 41% vs 34% in older patients; P = .01; and rectal cancer in 40% vs 35% in older patients; P = .29). Patients with young-onset CRC had a significantly longer median time to diagnosis (128 vs 79 days for older patients; P < .05), symptom duration (60 vs 30 days for older patients; P < .01), and time of evaluation (31 vs 22 days; P < .05). In multivariable analyses, time to diagnosis was 1.4-fold longer for younger than for older patients (P < .01). Among younger patients, those with stage III or IV CRC had shorter durations of symptoms and evaluations than those with stage I or II CRC. CONCLUSIONS: In a retrospective analysis of patients with CRC, we found that greater proportions of patients younger than 50 years were diagnosed with advanced-stage tumors than older patients; this difference could not be explained simply by delays from symptom onset to diagnosis. Although tumor biology may be an important determinant of stage at diagnosis, clinicians should be aware of CRC alarm symptoms, family history, and genetic syndromes, to speed evaluation and diagnosis of younger patients and potentially improve outcomes. It remains to be determined whether subgroups of persons at risk for young-onset CRC who benefit from early screening can be identified.

Imiquimod 5% cream as primary or adjuvant therapy for melanoma in situ, lentigo maligna type.

BACKGROUND: Surgical resection of lentigo maligna (LM) is complicated by noncontiguous, subclinical extension and actinic melanocytic hyperplasia in sun-damaged skin of older individuals. OBJECTIVE: We sought to determine the long-term effectiveness of imiquimod as primary or adjuvant therapy for LM. METHODS: Patients were retrospectively identified from January 1, 2003, to December 31, 2013, with LM, early/evolving LM, and LM melanoma who had used topical imiquimod 5% cream for either primary therapy after diagnostic biopsy, or adjuvant therapy after narrow-margin surgical resection or complete clinical but not histologic resection of LM. Follow-up occurred through December 31, 2014. RESULTS: In all, 63 cases were identified in 61 patients, mean (SD) age 71.1 (12.4) years; 58 were analyzed for local recurrence. Imiquimod was used as primary therapy in 22 of 63 (34.9%) and adjuvant therapy in 41 of 63 (65.1%) for mean duration of 11.7 (range 2-60) weeks. Fifty cases (86.2%) demonstrated clinical clearance at mean (SD) follow-up of 42.1 (27.4) months: 72.7% primary and 94.4% adjuvant at 39.7 (23.9) and 43.1 (28.9) months, respectively. LIMITATIONS: Retrospective cohort study and lack of standardized imiquimod application are limitations. CONCLUSION: Imiquimod cream appears to be a viable option for primary or adjuvant treatment of LM in older patients who are poor surgical candidates.

Impact of positron emission tomography/computed tomography surveillance at 12 and 24 months for detecting head and neck cancer recurrence.

BACKGROUND: In head and neck cancer (HNC), 3-month post-treatment positron emission tomography (PET)/computed tomography (CT) reliably identifies persistent/recurrent disease. However, further PET/CT surveillance has unclear benefit. The impact of post-treatment PET/CT surveillance on outcomes is assessed at 12 and 24 months. METHODS: A 10-year retrospective analysis of HNC patients was carried out with long-term serial imaging. Imaging at 3 months included either PET/CT or magnetic resonance imaging, with all subsequent imaging comprised of PET/CT. PET/CT scans at 12 and 24 months were evaluated only if preceding interval scans were negative. Of 1114 identified patients, 284 had 3-month scans, 175 had 3- and 12-month scans, and 77 had 3-, 12-, and 24-month scans. RESULTS: PET/CT detection rates in clinically occult patients were 9% (15 of 175) at 12 months, and 4% (3 of 77) at 24 months. No difference in outcomes was identified between PET/CT-detected and clinically detected recurrences, with similar 3-year disease-free survival (41% vs 46%, P = .91) and 3-year overall survival (60% vs 54%, P = .70) rates. Compared with 3-month PET/CT, 12-month PET/CT demonstrated fewer equivocal reads (26% vs 10%, P < .001). Of scans deemed equivocal, 6% (5 of 89) were ultimately found to be positive. CONCLUSIONS: HNC patients with negative 3-month imaging appear to derive limited benefit from subsequent PET/CT surveillance. No survival differences were observed between PET/CT-detected and clinically detected recurrences, although larger prospective studies are needed for further investigation.

Aberrant lymphatic drainage and risk for melanoma recurrence after negative sentinel node biopsy in middle-aged and older men.

BACKGROUND: Aberrant lymphatic drainage is believed to contribute to the high recurrence rate of head and neck melanomas. The purpose of this study was to identify the clinical significance of unexpected lymphatic drainage patterns. METHODS: A single institution retrospective analysis was performed of middle-aged and older men (mean age, 66.2 years; range, 41-87 years) who underwent successful lymphoscintigraphy with sentinel lymph node biopsy (SLNB) from 1997 through 2012. Node status, distribution, and recurrence were assessed comparing patients with expected and unexpected drainage patterns. RESULTS: Sixty-six patients were identified with 55.8 months median follow-up (range, 5.6-206.1 months). Unexpected sentinel lymph node drainage was associated with multiple basin drainage (p < .01) and greater recurrence after negative SLNB (p = .03). Both groups had similar anatomic distribution, sentinel lymph node sampling, histopathologic characteristics, follow-up, and survival. CONCLUSION: Lymphatic drainage differing from expected patterns is associated with greater recurrence after negative SLNB in middle-aged and older men. © 2015 Wiley Periodicals, Inc. Head Neck 38: E754-E760, 2016.

Involution of eruptive melanocytic nevi on combination BRAF and MEK inhibitor therapy.

IMPORTANCE: Eruptive melanocytic nevi (EMN) are characterized by the sudden onset of numerous melanocytic nevi and have been traditionally described in the setting of immunosuppression. Selective BRAF inhibitors such as vemurafenib cause multiple cutaneous adverse effects, including the formation of cutaneous squamous cell carcinoma, as well as EMN. We describe the first reported case, to our knowledge, of involution of BRAF inhibitor-induced EMN following the concomitant addition of a MEK inhibitor, cobimetinib. OBSERVATIONS: A woman in her 20s with a history of metastatic melanoma developed EMN while receiving therapy with vemurafenib, a selective BRAF inhibitor. After disease progression, the patient was placed on a clinical trial that combined vemurafenib with a MEK inhibitor, cobimetinib. Within months, we noted clinical involution of many of her EMN. In addition, numerous preexisting nevi were noted to fade in color on the dual regimen. Over a year after initiating this combination therapy, most of the patient's EMN were no longer clinically evident. CONCLUSIONS AND RELEVANCE: Our case report describing the involution of EMN supports data from previous clinical trials indicating that combination BRAF and MEK inhibition may reduce cutaneous proliferative effects that arise on BRAF inhibitor monotherapy. Further studies are necessary to characterize the biological mechanisms underlying this phenomenon.

Acquired blue nevi in older individuals: retrospective case series from a Veterans Affairs population, 1991 to 2013.

IMPORTANCE: Apart from the atypical mole phenotype, development of new melanocytic nevi in older individuals is uncommon and considered worrisome for melanoma. We performed a retrospective case series in a Veterans Affairs population from 1991 to 2013 to characterize blue nevi (BN) by patient age at biopsy, location, self-reported duration, and relation to prior or subsequent development of cutaneous melanoma. OBSERVATIONS: A total of 204 BN were identified in 194 predominantly male patients (90.7%) who had a mean (SD) age of 62.8 (14.4) years. Clinical duration of 10 years or less was reported by 90.3% of patients with available data (32.0%). Histopathologic examination classified 74.0% of BN as common, 1.5% as cellular, and 24.5% as combined type. No malignant BN were identified; however, 18 primary melanomas were diagnosed, most (72.2%) prior to blue nevus biopsy, including 38.9% in situ and 61.1% with mean (SD) Breslow thickness of 1.02 (0.99) mm. CONCLUSIONS AND RELEVANCE: The later patient-reported onset of BN suggests a potential alternative mechanism of nevogenesis compared with common acquired nevi and differs from prior reports of BN development in younger adults. The lack of association with melanoma in older individuals suggests that most benign-appearing BN may be safely observed, even in a cohort at higher risk for skin cancer.