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AbstractBackgroundPheochromocytoma with synchronous ipsilateral adrenal cortical adenoma (PSCA) may present with mixed clinical, biochemical, and radiological features characteristic to each neoplasm subtype. MethodsAll patients with a pathological diagnosis of pheochromocytoma were evaluated for an ipsilateral cortical adenoma from 1994 through 2015. Retrospectively extracted data included indications for adrenalectomy, diagnostic workup (biochemical and radiographic), operative characteristics, pathological findings, and postoperative complications. ResultsSixteen of 413 patients (4%) undergoing adrenalectomy for pheochromocytoma had a PSCA. Median patient age was 57.7 years (IQR 50.1, 63.1); 50% were male. On imaging, 75% of the adrenal neoplasms were found incidentally and only 50% were reported to have a synchronous ipsilateral neoplasm based on imaging findings. Clinically important cortical hormone secretion was diagnosed in 38% of these patients; 25% had glucocorticoid secretory autonomy; and 13% had primary aldosteronism. ConclusionPhysicians should be aware that adrenal neoplasms with mixed diagnostic findings may represent PSCA. Evaluation should be performed on this co‐occurrence to prevent perioperative complications from resection of an unexpected secretory cortical neoplasm.

Objectives: The incidence of second anterior cruciate ligament (ACL) injury after ACL reconstruction (ACLR) and return to sport (RTS) in a young, active population is likely between 25-33% with the greatest risk in the first 12 months after RTS. Although the use of allograft tissue in young athletes has been reported to result in increased risk of graft failure, differences in graft and contralateral ACL injury risk between patients who receive a hamstrings (HS) autograft and bone-patellar tendon- bone (BTB) autograft has yet to be reported in a young, athletic population. The tested hypothesis was that the relative risk (RR) of ipsilateral graft failure would be higher in young, active patients who receive an ACLR with a hamstrings graft, while the RR of contralateral ACL injury would be higher in patients who receive and ACLR with a BTB autograft. Methods: One hundred thirty-nine subjects (99 female/40 male) with a mean age of 16.9±2.0 years old (range: 13-25 y/o) underwent ACLR with either a HS autograft (n=79) or a BTB autograft (n=60) and were released to return to pivoting/cutting sport. These patients were enrolled in a prospective, observational cohort study and were tracked for incidence of 2 nd ACL after ACLR for a median of 73 months. Thirty-four (24.5%) suffered a 2 nd ACL injury. Fisher’s exact tests were used to determine whether graft choice (HS vs. BTB) was associated with risk of either ipsilateral graft failure or contralateral ACL injury. Sub-group analyses by sex were also conducted. Results: Patients who underwent ACLR with HS graft (n=79) sustained 14 ipsilateral tears and 6 contralateral ACL injuries. Patients who received an ACLR with BTB (n=62) sustained 2 ipsilateral tears and 12 contralateral ACL injuries (Table 1). Patients who received an ACLR with HS graft were 6 times more likely (RR=6.2; 95% CI: 1.4-28.7) to suffer a graft failure after RTS than the BTB group. In the first 12 months after RTS, the HS graft patients were nearly 10 times (RR=9.5; 95% CI: 1.2-76.1) more likely to suffer an ipsilateral graft failure. Patients with a HS graft were 3 times less likely (RR=0.33; 95%CI: 0.12-0.935) to suffer a contralateral ACL injury and nearly 7 times less likely (RR=0.15, 95%CI: 0.031-0.709) to suffer a contralateral ACL injury in the first 12 months after RTS compared to the BTB group. When the cohort was divided by sex, females with HS grafts were significantly more likely to sustain a graft failure in the first 12 months after RTS (p=0.008) and by final follow-up (p=0.002) compared to females with BTB graft. Females with HS grafts were 3 times less likely (RR=0.30; 95%CI: 0.095-0.943) to suffer a contralateral ACL injury than females with BTB graft and 6 times less likely (RR=0.17; 95%CI: 0.034-0.846) to suffer contralateral ACL injury in the first year after RTS. Males demonstrated no significant difference in ipsilateral or contralateral injury risk based on graft type. Conclusion: Young, active females who return to pivoting and cutting sports after ACLR with HS autograft are at greater risk to suffer a graft failure and reduced risk to suffer a contralateral ACL injury compared to females who undergo ACLR with BTB graft tissue. No significant differences in 2 nd ACL injury risk based on graft type were observed in the male patients. [Table: see text]

Summary Objective The outcomes of patients with metastatic phaeochromocytoma (PHEO) and paraganglioma (PGL) are unclear. We performed a systematic review and meta‐analysis of baseline characteristics and mortality rates of patients with metastatic PHEO and PGL (PPGL). Design Ovid MEDLINE In‐Process & Other Non‐Indexed Citations, Ovid MEDLINE, Ovid EMBASE, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, Scopus, Web of Science, and references of key articles were searched from inception to 2016. Patients Studies comprised ≥20 patients with metastatic PPGL and reported baseline characteristics and follow‐up data. Measurements Reviewers extracted standardized data and assessed risk of bias using a modified Newcastle‐Ottawa tool. Random‐effects meta‐analysis was used to pool event rates across studies. Results Twenty retrospective noncomparative studies reported on 1338 patients with metastatic PHEO (685/1296, 52.9%) and PGL (611/1296, 47.1%), diagnosed at a mean age of 43.9 ± 5.2 years. Mean follow‐up was 6.3 ± 3.2 years. Of 532 patients with reported data, 40.4% had synchronous metastases. Five‐year (7 studies, n = 738) and 10‐year (2 studies, n = 55) mortality rates for patients with metastatic PPGL were 37% (95% CI, 24%‐51%) and 29% (95% CI, 17%‐42%), respectively. Higher mortality was associated with male sex (RR 1.50; 95% CI, 1.11‐2.02) and synchronous metastases (RR 2.43; 95% CI, 1.01‐5.85). Conclusions Available low‐quality evidence from heterogeneous studies suggests low mortality rates of patients with metastatic PPGL. Male sex and synchronous metastases correlated with increased mortality. The outcomes of patients with metastatic PPGL have been inadequately assessed, indicating the need for carefully planned prospective studies.

Thirty‐six weanling guinea pigs were fed either a low (600 ppm) or normal (3000 ppm) diet of magnesium for 8 weeks. One half of each diet group received intramuscular injections of magnesium‐depleting drugs, furosemide and gentamicin. The other half were controls and received equal intramuscular injections of saline. Auditory brainstem responses were obtained from all animals before and after 8 weeks of treatment of diet and drugs to examine the effects of treatment upon hearing and auditory brainstem function. A three‐way analysis of variance of dietary magnesium, by drug and by sex, showed no significant differences in auditory brainstem wave V thresholds, wave V latencies, or interpeak wave I‐V latencies between the control and experimental groups. The low magnesium diet group, which received drugs, had significantly greater wave V auditory brainstem response amplitudes. Results can be explained on the basis of magnesium influencing the uptake of calcium into both the hair cells and associated brainstem pathways.

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4076 Background: Gallbladder carcinoma (GBC) is commonly diagnosed at an advanced, unresectable disease stage and has a poor prognosis. Comprehensive genomic profiling (CGP) has a developing role in guiding systemic, precision anti-cancer therapy. Methods: We performed hybrid capture-based CGP on FFPE samples for 491 consecutive advanced GBCs. Mean coverage depth was >550X for up to 315 cancer-related genes plus 37 introns from 28 genes frequently rearranged in cancer. All 4 classes of genomic alterations (GA) were detected. Tumor mutational burden (TMB) was determined on up to 1.1 Mb of sequenced DNA. Results: Median age was 64 (range 25-88) and 69% (337/491) of patients were female. 96% (470), 2.9% (14), and 1.4% (7) of GBC patients had the diagnosis of adenocarcinoma, adenosquamous, or carcinoma not specified (NOS), respectively. Commonly altered genes were TP53 (62%), CDNK2A (31%), ARID1A (18%), and SMAD4 (15%), and most of the genetic aberrations (GA) were short variants. Potentially targetable SCNAs (including ERBB genes, MET, FGFRs, and the CCND1-FGF3/4/19 11q13 amplicon) were identified in 21% of cases (Table). Oncogenic BRAF, ALK, or FGFR2/3 rearrangements were found in 7 cases (1.4%). Moreover, 7.8% of cases had BRCA2 or ATM GA, and 0.8% had INI1loss suggesting benefit from PARP or EZH2 inhibitors, respectively. TMB was low; the 25th, 50th, and 75th percentiles were 2.5, 3.8 and 6.3 mutations/Mb, respectively. Less than 1% of cases had microsatellite instability. Radiological response to TKIs and immunotherapy was noted. Conclusions: In addition to the significant opportunity for anti-HER targeted therapies, other subsets of GBC cases harbored kinase GA (particularly SCNA), the 11q13 amplicon, or BRCA2/ ATM/ INI1mutations that are linked to therapeutic benefit. How the frequency of both driver SCNA and DNA repair alterations in GBC can be linked with inflammation awaits additional investigation. [Table: see text]

Objectives/HypothesisSarcomatoid carcinoma is a rare variant of squamous cell carcinoma of the head and neck. No consensus exists on its management. Our aim was to present our outcomes.Study DesignRetrospective study. Median follow‐up 45 months.MethodsThere were 38 patients with pathologically confirmed sarcomatoid carcinoma of the larynx treated at the Mayo Clinic from 1990 to 2014. Statistical analysis of overall survival (OS), progression‐free survival (PFS), and local control (LC) were conducted using the Kaplan‐Meier method.ResultsThe majority of patients were elderly males (92%) with a smoking history (74%) presenting with early‐stage disease (71%). Surgery alone was the primary treatment in 27 patients (71%). Nine patients (25%) were treated with adjuvant radiation due to initial stage or high‐risk pathologic features. Median radiation dose to the primary/surgical bed was 65 Gy (range, 60.3–75.0 Gy). A total of 15 patients (39%) had tumor recurrence, majority being local (n = 12). Sixty percent (n = 9) had multiple local recurrences. Five‐year OS, PFS, and LC were 63%, 46%, and 72%, respectively. Subgroup analysis by stage I versus higher stages (II–IV) showed an OS of 80% versus 43% (P = .030), PFS of 65% versus 18% (P = .003), and LC of 84% versus 57% (P = .039).ConclusionsSarcomatoid carcinoma of the larynx is rare, and frequently presents at an early stage in older men with history of smoking. Based on our outcomes and patterns of failure, it appears early‐stage tumors are treated appropriately with single‐modality therapy, whereas more advanced tumors require multimodality therapy. Validation in a larger cohort is warranted.Level of Evidence4. Laryngoscope, 128:373–377, 2018