Higher SUVmax on FDG-PET is associated with shorter survival in adrenocortical carcinoma.

BACKGROUND: Adrenocortical carcinoma (ACC) is an aggressive, rare malignancy. 2-deoxy-2-[18F]-fluoro-d-glucose positron emission tomography (FDG-PET) assesses tumor metabolism and glucose utilization. We hypothesized that higher maximum standard uptake value (SUVmax) is associated with decreased survival. METHODS: We performed a retrospective analysis of patients with ACC. Included patients (n = 26) had an FDG-PET scan available with a documentable SUVmax. Patients were dichotomized into "High" (≥8.4, n = 12) and "Low" (<8.4, n = 14) SUVmax. Univariate analysis and survival analysis were performed to compare groups. RESULTS: Demographics between groups were equivalent. The high SUVmax cohort demonstrated lower survival (median 479 days or 15.7 months) compared to the low group (median 1490 days or 48.6 months, p = .01). Log-Rank curve confirmed differences in survival (p = .007). CONCLUSIONS: Higher SUVmax was associated with significantly worse survival in ACC and may reflect a more aggressive phenotype. FDG-PET may provide clinically useful information to determine prognosis and treatment. Further studies should prospectively evaluate using FDG-PET/CT in ACC.

Evaluating the Rising Incidence of Thyroid Cancer and Thyroid Nodule Detection Modes: A Multinational, Multi-institutional Analysis.

Importance: There is epidemiologic evidence that the increasing incidence of thyroid cancer is associated with subclinical disease detection. Evidence for a true increase in thyroid cancer incidence has also been identified. However, a true increase in disease would likely be heralded by an increased incidence of thyroid-referable symptoms in patients presenting with disease. Objectives: To evaluate whether modes of detection (MODs) used to identify thyroid nodules for surgical removal have changed compared with historic data and to determine if MODs vary by geographic location. Design, Setting, and Participants: This was a retrospective analysis of pathology and medical records of 1328 patients who underwent thyroid-directed surgery in 16 centers in 4 countries: 4 centers in Canada, 1 in Denmark, 1 in South Africa, and 12 in the US. The participants were the first 100 patients (or the largest number available) at each center who had thyroid surgery in 2019. The MOD of the thyroid finding that required surgery was classified using an updated version of a previously validated tool as endocrine condition, symptomatic thyroid, surveillance, or without thyroid-referable symptoms (asymptomatic). If asymptomatic, the MOD was further classified as clinician screening examination, patient-requested screening, radiologic serendipity, or diagnostic cascade. Main Outcomes and Measures: The MOD of thyroid nodules that were surgically removed, by geographic variation; and the proportion and size of thyroid cancers discovered in patients without thyroid-referable symptoms compared with symptomatic detection. Data analyses were performed from April 2021 to February 2022. Results: Of the 1328 patients (mean [SD] age, 52 [15] years; 993 [75%] women; race/ethnicity data were not collected) who underwent thyroid surgery that met inclusion criteria, 34% (448) of the surgeries were for patients with thyroid-related symptoms, 41% (542) for thyroid findings discovered without thyroid-referable symptoms, 14% (184) for endocrine conditions, and 12% (154) for nodules with original MOD unknown (under surveillance). Cancer was detected in 613 (46%) patients; of these, 30% (183 patients) were symptomatic and 51% (310 patients) had no thyroid-referable symptoms. The mean (SD) size of the cancers identified in the symptomatic group was 3.2 (2.1) cm (median [range] cm, 2.6 [0.2-10.5]; 95% CI, 2.91-3.52) and in the asymptomatic group, 2.1 (1.4) cm (median [range] cm, 1.7 [0.05-8.8]; 95% CI, 1.92-2.23). The MOD patterns were significantly different among all participating countries. Conclusions and Relevance: This retrospective analysis found that most thyroid cancers were discovered in patients who had no thyroid-referable symptoms; on average, these cancers were smaller than symptomatic thyroid cancers. Still, some asymptomatic cancers were large, consistent with historic data. The substantial difference in MOD patterns among the 4 countries suggests extensive variations in practice.

The glass podium: Gender representation within the American Association of Endocrine Surgeons (AAES) from 2010 to 2019.

BACKGROUND: Despite increasing numbers of women in surgery, female underrepresentation in surgical societies remains an ongoing issue. We sought to determine the gender composition of presenters at the American Association of Endocrine Surgery annual meetings. METHODS: Utilizing previous meeting data, we collected gender information for presenters from 2010 to 2019, including first/senior author combinations. Awards winners and invited lecturers were also reviewed. We performed binomial testing to analyze proportions of male to female presenters, with significance set at P < .05. Temporal trends were analyzed via linear regression. RESULTS: Fifty-six percent of American Association of Endocrine Surgery fellows and 36% of members are female. Of 354 podium and 477 poster presentations, women were listed less often as first (42.7%, P = .007) and senior (30.6%, P < .0001) podium authors and less often as first (42.8%, P = .002) and senior (29.8%, P < .0001) poster authors. The most common combination of first/senior authors was male-male (43.1%), followed by female-male (26.8%), female-female (16.1%), and male-female (14.0%). Less than 15% of invited lecturers were women, and women represented a minority in nearly all award categories. We observed a positive trend in female first authorship over time (slope = 0.766, 95% confidence interval, 0.70%-2.23%, P = .26) but no change in female senior authorship over time (slope = 0.03348, 95% confidence interval, 1.086%-1.153%, P = .95). CONCLUSION: Women are underrepresented as American Association of Endocrine Surgery presenters and less likely to receive awards or deliver invited lectures. Although female first authorship increased over time, women continued to lag behind men as senior authors and mentors to trainees and junior faculty. Opportunities to improve speaker and awardee representation should be explored.

Diabetes mellitus and hyperglycemia are associated with inferior oncologic outcomes in adrenocortical carcinoma.

PURPOSE: Prior literature suggests that cancer patients with hyperglycemia and type 2 diabetes mellitus (DM) exhibit worse oncologic and overall outcomes. Tumor metabolism and anabolism pathophysiology may explain this association, although this has not been adequately studied in adrenocortical carcinoma (ACC). We hypothesized that DM would be associated with worse oncological outcomes in ACC, and we utilized data from a national database and institutional sources for multimodal analysis. METHODS: Both a multi-institutional database (the Collaborative Endocrine Surgery Quality Improvement Program or CESQIP) and a single-center longitudinal cohort (Dana Farber Cancer Institute or DFCI) were queried as unique retrospective cohorts to identify patients with ACC. Patient demographics, tumor characteristics, DM-specific variables, and oncologic outcome data were assessed. Results were analyzed via univariate analysis and multivariable linear regression analysis. Statistical significance was defined as p < 0.05. RESULTS: Forty-eight CESQIP patients met inclusion criteria; 16 (33.0%) had DM. DM patients had a higher frequency of recurrence on longitudinal follow-up (12.5% v 0.0%, p = 0.04). Persistent disease was observed in 68.8% of DM patients and 40.6% of non-DM patients (p = 0.06). Patients in the DFCI cohort with lower average glucose values (< 110 mg/dL) had a significant survival benefit (p < .0001). A mean serum glucose > 110 mg/dL had increased risk (HR 36.3, 95% confidence interval 1.6, 831.3) for all-cause mortality. CONCLUSIONS: This multi-institutional, multimodal analysis suggests that patients with DM have worse oncologic and overall outcomes for ACC. While further study is warranted, consideration should be given among clinicians to optimize glycemic control as part of their ACC management.

Practice patterns for surgical management of low-risk papillary thyroid cancer from 2014 to 2019: A CESQIP analysis.

BACKGROUND: Patients with low-risk-PTC who undergo thyroid lobectomy (TL) have comparable disease-specific survival with lower morbidity than total thyroidectomy (TT). We aim to describe the surgical management of low-risk-PTC using the Collaborative Endocrine Surgery Quality Improvement Program (CESQIP). METHOD: CESQIP thyroidectomies of PTC tumors <4 cm were analyzed from 2014 to 2019 (n = 740). Postoperative outcomes were compared. Subgroup analysis examined temporal and institutional trends, and stratified for tumor size. Statistics utilized t-test, ANOVA, and Chi-squared. RESULTS: TT patients had greater hypoparathyroidism, operative time, and length-of-stay (all p < 0.001). Incidence of TL decreased with increasing tumor size (24.2% for <1 cm, 15.8% for 1-2 cm, 6.1% for 2-4 cm). TL rates increased from 2.0% in 2014 to 21.2% in 2018-19. Completion thyroidectomy was recommended in 12.0% of TL subjects. There was significant variation in TL rate by institution (p < .001). CONCLUSIONS: For low-risk-PTC, TT remained the most commonly utilized operation. TL rates increased following release of the new ATA guidelines. TT was associated with higher perioperative morbidity. Further insight is needed to understand factors influencing operative approach.

Primary aldosteronism.

Primary aldosteronism (PA) is a common cause of secondary hypertension caused by excessive and inappropriate secretion of the hormone aldosterone from one or both adrenal glands. The prevalence of PA ranges from 10% in the general hypertensive population to 20% in resistant hypertension, yet only a small fraction of patients is diagnosed. Disease and symptom recognition, screening in indicated populations, multidisciplinary communication, and appropriate imaging and biochemical workup can identify patients who might benefit from effective and targeted treatment modalities. Effective treatments available include both surgical and medical approaches, usually dependent on the subtype of PA present. Our collective understanding of the pathophysiology of PA is expanded by recent developments in molecular biology and genetics, including understanding the specific somatic and germline mutations involved in pathogenesis. We review the pathophysiology, diagnostic workup, and treatment considerations for this disease process.

Patient Perceptions and Quality of Life After Colon and Rectal Surgery: What Do Patients Really Want?

BACKGROUND: Colorectal surgery outcomes must be accurately assessed and aligned with patient priorities. No study to date has investigated the patient's subjective assessment of outcomes most important to them during and following their surgical recovery. Although surgeons greatly value the benefits of laparoscopy, patient priorities remain understudied. OBJECTIVE: This study aimed to assess what aspects of patients' perioperative care and recovery they value most when queried in the postoperative period. DESIGN: This study is an exploratory cross-sectional investigation of a defined retrospective patient population. Enrollees were stratified into subcategories and analyzed, with statistical analysis performed via χ test and unpaired t test. SETTINGS: This study was conducted at a single academic medical center in New England. PATIENTS: Patients who underwent a colorectal surgical resection between 2009 and 2015 were selected. INTERVENTIONS: Patients within a preidentified population were asked to voluntarily complete a 32-item questionnaire regarding their surgical care. MAIN OUTCOME MEASURES: The primary outcomes measured were patient perioperative and postoperative quality of life and satisfaction on selected areas of functioning. RESULTS: Of 167 queried respondents, 92.2% were satisfied with their recovery. Factors considered most important included being cured of colorectal cancer (76%), not having a permanent stoma (78%), and avoiding complications (74%). Least important included length of stay (13%), utilization of laparoscopy (14%), and incision appearance and length (2%, 4%). LIMITATIONS: The study had a relatively low response rate, the study is susceptible to responder's bias, and there is temporal variability from surgery to questionnaire within the patient population. CONCLUSIONS: Overall, patients reported high satisfaction with their care. Most important priorities included being free of cancer, stoma, and surgical complications. In contrast, outcomes traditionally important to surgeons such as laparoscopy, incision appearance, and length of stay were deemed less important. This research helps elucidate the outcomes patients truly consider valuable, and surgeons should focus on these outcomes when making surgical decisions. See Video Abstract at http://links.lww.com/DCR/A596. See Visual Abstract at https://tinyurl.com/yb25xl66.

Improving the performance of virtual crossmatch results by correlating with nationally-performed physical crossmatches: Obtaining additional value from proficiency testing activities.

PURPOSE: When donor specific HLA antibodies (DSA) are identified, the predictive value of whether a certain strength of reactivity (mean fluorescence intensity, MFI) leads to a positive crossmatch is uncertain. To determine this, we compared the DSA MFI results we generated locally for nationally distributed proficiency samples against the percentage of other laboratories reporting a positive crossmatch. METHOD: DSA MFI from single antigen beads reported by our laboratory for nationally-distributed proficiency testing survey samples was compared against the aggregate percentage of participating laboratories reporting the crossmatch positive using direct, antiglobulin-enhanced microcytotoxic (CDC-AHG), or flow cytometric methods from 2011 to 2015. RESULTS: 180 surveys were analyzed. Positive CDC-AHG and flow cytometric crossmatches were associated with MFI greater than 8554 and 2748 respectively for HLA class I, and 6919 and 3707 respectively for class II. Institutional MFI less than 3000 had high positive predictive values (0.98, 0.85, 0.81) for negative direct, AHG, and flow crossmatches, while MFI greater than 8000 had high negative predictive values for a positive direct, AHG, and flow crossmatches (1.00, 1.00, 0.97). CONCLUSION: Review of locally-generated MFI results as part of participating in proficiency testing allow for predictability of crossmatch results against other laboratories, providing a replicable model for other participating centers.

Avian lungs: A novel scaffold for lung bioengineering.

Allogeneic lung transplant is limited both by the shortage of available donor lungs and by the lack of suitable long-term lung assist devices to bridge patients to lung transplantation. Avian lungs have different structure and mechanics resulting in more efficient gas exchange than mammalian lungs. Decellularized avian lungs, recellularized with human lung cells, could therefore provide a powerful novel gas exchange unit for potential use in pulmonary therapeutics. To initially assess this in both small and large avian lung models, chicken (Gallus gallus domesticus) and emu (Dromaius novaehollandiae) lungs were decellularized using modifications of a detergent-based protocol, previously utilized with mammalian lungs. Light and electron microscopy, vascular and airway resistance, quantitation and gel analyses of residual DNA, and immunohistochemical and mass spectrometric analyses of remaining extracellular matrix (ECM) proteins demonstrated maintenance of lung structure, minimal residual DNA, and retention of major ECM proteins in the decellularized scaffolds. Seeding with human bronchial epithelial cells, human pulmonary vascular endothelial cells, human mesenchymal stromal cells, and human lung fibroblasts demonstrated initial cell attachment on decellularized avian lungs and growth over a 7-day period. These initial studies demonstrate that decellularized avian lungs may be a feasible approach for generating functional lung tissue for clinical therapeutics.

Three decades later: investigating the rate of and risks for conversion from laparoscopic to open cholecystectomy.

INTRODUCTION: Recent data suggest a wide range of conversion (4.9-20%) from laparoscopic (LC) to open cholecystectomy (OC) despite increasing surgeon familiarity and superior equipment. Previously identified risk factors for conversion include increased age, male gender, diabetes, and emergent surgeries. Recent studies also suggest that formal minimally invasive surgical training (MIST) reduces conversion rates. We sought to determine conversion rates in our population, a rural academic medical center, and identify any significant risks for conversion. METHODS: We conducted a single-center retrospective review of 2810 cholecystectomies performed over a seven-year period (2009-2016). RESULTS: Our study included 837 (29.8%) males and 1973 (70.2%) females with a mean age of 49.2 years. Forty-two percent of cases were done by surgeons with MIST. A total of 139 (4.95%) cases were converted to OC. Univariate predictors of conversion to OC included male gender, age ≥65, urgent and emergent admissions, and MIST of the surgeon. In multivariate modeling, which included significant univariate predictors of conversion, independent predictors of conversion to OC included urgent or emergent admission, male gender, and age ≥65. MIST status was no longer a significant predictor. CONCLUSION: Our conversion rate from LC to OC falls within the lower range of recently published rates. This is likely multifactorial, and reflects increasing familiarity of the laparoscopic technique, improved quality of laparoscopic equipment, and/or prior knowledge of preoperative risk factors for conversion. Our results, consistent with previous literature, show a reduced conversion rate among surgeons with MIST. This finding, albeit not significant on multivariate analysis, may offer insight into a potential alterable preoperative risk factor for conversion and warrants further research. Further knowledge about the impact MIST has on conversion may provide a feasible preoperative approach to reducing conversion to OC, thereby reducing costs and overall patient morbidity.

Cost Analysis and Supply Utilization of Laparoscopic Cholecystectomy.

Laparoscopic cholecystectomy (LC) is one of the highest volume surgeries performed annually. We hypothesized that there is a statistically significant intradepartmental cost variance with supply utilization variability amongst surgeons of different subspecialty. This study sought to describe laparoscopic cholecystectomy cost of care among three subspecialties of surgeons. This retrospective observational cohort study captured 372 laparoscopic cholecystectomy cases performed between June 2015 and June 2016 by 12 surgeons divided into three subspecialties: 2 in bariatric surgery (BS), 5 in acute care surgery (ACS), and 5 in general surgery (GS). The study utilized a third-party software, Surgical Profitability Compass Procedure Cost Manager and Crimson System (SPCMCS) (The Advisory Board Company, Washington, DC), to stratify case volume, supply cost, case duration, case severity level, and patient length of stay intradepartmentally. Statistical methods included the Kruskal-Wallis test. Average composite supply cost per case was $569 and median supply cost per case was $554. The case volume was 133 (BS), 109 (ACS), and 130 (GS). The median intradepartmental total supply cost was $674.5 (BS), $534 (ACS), and $564 (GS) (P<0.005). ACS and GS presented with a higher standard deviation of cost, $98 (ACS) and $110 (GS) versus $26 (BS). The median case duration was 70 min (BS), 107 min (ACS), and 78 min (GS) (P<0.02). The average patient length of stay was 1.15 (BS), 3.10 (ACS), and 1.17 (GS) (P<0.005). Overall, there was a statistically significant difference in median supply cost (highest in BS; lowest in ACS and GS). However, the higher supply costs may be attenuated by decreased operative time and patient length of stay. Strategies to reduce total supply cost per case include mandating exchange of expensive items, standardization of supply sets, increased price transparency, and education to surgeons.

Increased risk organ transplantation in the pediatric population.

IRD organs are classified by the Public Health Service to be at above-average risk for harboring human immunodeficiency virus, hepatitis C, and hepatitis B. Traditionally underutilized, there exists even greater reluctance for their use in pediatric patients. We performed a retrospective analysis via the United Network for Organ Sharing database of all pediatric renal and hepatic transplants performed from 2004 to 2008 in the United States. Primary outcomes were patient and graft survival. Proportional hazards regression was performed to control for potentially confounding factors. Waitlist time, organ acceptance rates, and infectious transmissions were analyzed. There were 1830 SRD renal, 92 IRD renal, 1695 SRD hepatic, and 59 IRD hepatic transplants. There were no statistically significant differences in allograft or patient survival in either group. Acceptance rates of IRD organs were lower for kidney (1.5% IRD vs 4.82% SRD) and liver (1.99% IRD vs 4.51% SRD). One transmission of a bloodborne pathogen involving a pediatric recipient out of 7797 unique transplants was reported from 2008 to 2015. IRD organs appear to have equivalent outcomes. Increasing their utilization may improve access to transplant while decreasing wait times and circumventing waitlist morbidity and mortality.

Acute large bowel pseudo-obstruction due to atrophic visceral myopathy: A case report.

PURPOSE: Atrophic visceral myopathy is a pathological diagnosis characterized by atrophy of the smooth muscle layers of the viscera with intact ganglia. Rarely, it can present acutely as an intestinal pseudo-obstruction. We describe a rare case report and explore how this diagnosis can be distinguished from other forms of intestinal obstruction. CASE DESCRIPTION: A 60-year-old male with a past medical history of hypothyroidism presented to the emergency department with a two-day history of worsening abdominal distention and pain associated with nausea and vomiting. Upon evaluation patient was found to have tachycardia, with abdominal distention and localized tenderness with peritonitis. Computed tomography demonstrated large bowel obstruction, likely caused by sigmoid volvulus. The patient underwent emergent laparotomy. Intra-operatively, the entire colon was found to be extremely dilated and redundant. With a working diagnosis of recurrent sigmoid volvulus causing intermittent large bowel obstruction, a sigmoid colectomy and primary anastomosis was performed. Pathology revealed atrophic visceral myopathy, with an extremely thin colonic wall and atrophic circumferential and longitudinal muscularis propria without inflammation or fibrosis. The ganglion cells and myenteric plexus were unaffected. Post-operatively, the patient developed prolonged ileus requiring nasogastric decompression and parenteral nutrition. The ileus resolved with pro-kinetic agents, and patient was discharged home on post-operative day fifteen. CONCLUSIONS: Atrophic visceral neuropathy is a rare cause of intestinal pseudo-obstruction. While often presenting with chronic obstruction in younger populations, we present a rare late-onset acute presentation that may have been secondary to underlying hypothyroidism.

Histopathological examination of specimen following cholecystectomy: Are we accepting resect and discard?

BACKGROUND: Cholecystectomy is one of the most commonly performed general surgery procedures in the USA. It is most frequently performed for benign biliary disease such as biliary colic or cholecystitis; however, resected specimens are frequently sent for histopathological analysis due to the perceived risk of incidental gallbladder carcinoma (iGBC). The principle aim of this study is to review the pathology results from gallbladder specimens sent for routine pathology, determine the incidence of iGBC in our population, and determine whether surgeons need to send specimens for further analysis if no preoperative or intraoperative suspicion for malignancy is present. METHODS: We performed a large single-center case-controlled retrospective study of all gallbladder specimens sent for routine histopathological analysis between 2009 and 2014. The results were tabulated, including both common and rare findings. We then analyzed patient outcomes and survival for the case group of iGBC patients and determined value in life years (LY) gained per dollar spent on pathological screening. RESULTS: A total of 2153 pathology reports were reviewed. After exclusion criteria, a total of 1984 were included in data analysis. The incidence of iGBC was 0.25 % (95 % CI 0.08, 0.59), and dysplasia was 0.70 % (0.39, 1.20). The most common pathological findings included chronic cholecystitis in 89 % (87.4, 90.3) and cholelithiasis in 81 % (79.1, 82.6) of specimens. Total charges for pathological screening were $65,404 per LY to date; however, two patients have ongoing disease-free survival and this figure is expected to decrease. CONCLUSIONS: The incidence of significant pathology necessitating change in clinical management is extremely low in our population. Despite this, the cost per LY gained from routine pathological analysis appears to be of sufficient value to continue with current practice. Alternatively, selective screening based on risk factors, intraoperative findings, and on-table examination of specimen may be a more cost-effective approach.

Cycloheximide impairs and enhances memory depending on dose and footshock intensity.

This experiment examined the effects on memory of interactions of cycloheximide dose and training foot shock intensity. Mice received injections of cycloheximide (120 mg/kg, s.c.) or saline 30 min prior to inhibitory avoidance training with shock intensities of 100, 150, 250 or 300 µA (1 s duration). Memory was tested 48 h later. The saline control mice showed increasing memory latencies as a function of shock intensity. The ability of cycloheximide to impair memory increased as the training shock intensity increased. In a second experiment, mice were trained with a 200 µA (1 s duration) shock and received injections of saline or cycloheximide at one of several doses (30, 60 or 120 mg/kg). Under these training conditions, cycloheximide enhanced memory in an inverted-U dose-response manner. These findings are consistent with prior findings suggesting that protein synthesis inhibitors act on memory by altering modulators of memory formation as a secondary consequence of the inhibition of protein synthesis rather than by interfering with training-initiated synthesis of proteins required for memory formation.