Expression of the Calcium-Sensing Receptor on Normal and Abnormal Parathyroid and Thyroid Tissue.

INTRODUCTION: Current imaging techniques have several limitations in detecting parathyroid glands. We have investigated the calcium-sensing receptor (CaSR) as a potential target for specifically labeling parathyroid glands for radiologic detection. For accurate imaging it is vital that a large differential expression exists between the target tissue and adjacent structures. We sought to investigate the relative abundance of the CaSR in normal and abnormal parathyroid tissue, as well as normal and abnormal thyroid. METHODS: Existing clinical specimens were selected that represented a wide variety of pathologically and clinically confirmed malignant and benign thyroid and parathyroid specimens. Sections were stained for the CaSR using immunohistochemistry and scored for intensity and abundance of expression. (H score = intensity scored from 0 to 3 multiplied by the % of cells at each intensity. Range 0-300). RESULTS: All parathyroid specimens expressed the CaSR to a high degree. Normal parathyroid had the highest H score (271, s.d. 25.4). Abnormal parathyroid specimens were slightly lower but still much higher than normal thyroid (H score 38.3, s.d. 23.3). Medullary thyroid cancer also expressed the CaSR significantly higher than normal thyroid (H score 182, s.d. 69.1, P < 0.001) but below parathyroid levels. Hürthle cell carcinoma expressed the CaSR to a lesser degree but higher than normal thyroid (H score 101, s.d. 46.4, P = 0.0037). CONCLUSIONS: The CaSR is differentially expressed on parathyroid tissue making it a feasible target for parathyroid imaging. False positives might be anticipated with medullary and Hürthle cell cancers.

Expanding the role of PSMA PET in active surveillance.

INTRODUCTION: Accurate grading at the time of diagnosis is fundamental to risk stratification and treatment decision making, particularly for men being considered for Active Surveillance (AS). With the introduction of prostate-specific membrane antigen (PSMA) positron emission tomography (PET) there has been considerable improvement in sensitivity and specificity for the detection and staging of clinically significant prostate cancer. Our study aims to determine the role of PSMA PET/CT in men with newly diagnosed low or favourable intermediate risk prostate cancer to better select men for AS. METHOD: This is a retrospective single centre study performed from January 2019 and October 2022. This study includes men identified from electronic medical record system who had undergone a PSMA PET/CT following newly diagnosed low or favourable-intermediate risk prostate cancer. Primary outcome was to assess the change in management for men being considered for AS following PSMA PET/CT results on the basis of PSMA PET characteristics. RESULTS: In total, there were 11 of 30 men (36.67%) who were assigned management by AS and 19 of 30 men (63.33%) who had definitive treatment. 15 of the 19 men that needed treatment had concerning features on PSMA PET/CT results. Of the 15 men with concerning features on PSMA PET, 9 (60%) men were found to have adverse pathological features on final prostatectomy features. CONCLUSION: This retrospective study suggests that PSMA PET/CT has potential to influence the management of men with newly diagnosed prostate cancer that would otherwise be appropriate for active surveillance.

The effect of COVID-19 on prostate cancer testing in Australia.

AIM: The effects of the COVID-19 pandemic on healthcare in Australia have yet to be fully determined. There are well documented decreases in the rates of screening and diagnostic testing for many cancers in 2020, with commensurate stage migration of cancers when they are eventually detected. We aimed to determine whether there was a decrease in the rate of prostate cancer (PC) screening and testing in Australia in 2020. METHOD: Data was extracted from the Department of Human Services (DHS) website for Medicare Benefits Schedule (MBS) item numbers for tests pertinent to detection of Prostate Cancer. This data is de-identified and publicly available. Data was analysed at both a national, and a state level. RESULTS: For 2020 nationwide the percentage change for prostate cancer testing was minor with 97% as many PSA tests, 99% as many prostate MRIs, and 105% as many prostate biopsies as the average for the preceding years. The differences were not significant (PSA tests p = 0.059 and prostate biopsies p = 0.109). The predicted values are fairly similar to both the average values for the preceding 5 years and the actual number of tests done in 2020. With exception of PSA tests in Victoria the actual number of tests performed was within the 95% Prediction Interval (performed: 167,426; predicted 171,194-196,699; p = 0.015). CONCLUSION: The current pandemic has had a widespread reach across Australia, with varying impact across each state and territory. Contrary to the trends across the world, our data suggest that during 2020 in Australia most areas remained unaffected in terms of prostate cancer testing excluding Victoria, which had statistically significant decrease in the number of PSA tests correlating with the extended lockdown that occurred in the state.

A Systematic Review and Meta-Analysis of the Significance of Body Mass Index on Kidney Cancer Outcomes.

PURPOSE: Obesity is a well-known risk factor for kidney cancer incidence. However, a number of studies have demonstrated more favorable kidney cancer prognosis in patients with elevated body mass index conferring a survival advantage, termed the "obesity paradox." We aimed to evaluate the association between body mass index and kidney cancer outcomes (progression-free survival, cancer specific survival and overall survival). MATERIALS AND METHODS: A computerized systematic search of Medline®, Embase®, ProQuest®, PubMed® and Google Scholar™ for literature published in English was performed between its inception and December 2018, and Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were used for reporting. RESULTS: Overall, 34 publications comprising a total of 50,717 patients were included in the analysis. The majority assessed the association between body mass index and cancer specific survival. Overweight and obese patients were associated with improved cancer specific survival compared to patients with normal body mass index (HR 0.85, 95% CI 0.79-0.93). A similar trend was demonstrated for progression-free survival (HR 0.68, 95% CI 0.59-0.78) and overall survival (HR 0.66, 95% CI 0.55-0.79). On the contrary, the underweight group was associated with inferior cancer specific survival (HR 2.16, 95% CI 1.15-4.04). Main drawbacks limiting the interpretation were the retrospective design in the majority of studies, heterogeneity in study population, body mass index classification and covariates in multivariate analysis. CONCLUSIONS: This is the largest systematic review evaluating the potential phenomenon of the obesity paradox in kidney cancer outcomes. It demonstrated a favorable effect of body mass index on kidney cancer outcomes. However, due to significant heterogeneity of studies, multicenter prospective studies and further research on the fundamental biological mechanisms are warranted to confirm the significance of body mass index on kidney cancer prognosis.

A comparison of prostate cancer prediction models in men undergoing both magnetic resonance imaging and transperineal biopsy: Are the models still relevant?

OBJECTIVE: To externally validate and compare the performance of the European Randomized Study of Screening for Prostate Cancer risk calculator 3/4 (ERSPC-RC3/4), the Prostate Biopsy Collaborative Group risk calculator (PBCG-RC) and the van Leeuwen model to determine which prediction model would perform the best in a contemporary Australian cohort undergoing transperineal (TP) biopsy. MATERIALS AND METHODS: A retrospective review identified all patients undergoing TP biopsy across two centres. Of the 797 patients identified, 373 had the data required to test all three risk calculators. The probability of high-grade prostate cancer, defined as International Society of Urological Pathology Grade Group >1, was calculated for each patient. For each prediction model discrimination was assessed using area under the receiver-operating characteristic curve (AUC), calibration using numerical and graphical summaries, and net benefit using decision curve analysis. RESULTS: Assessment of model discrimination for detecting high-grade prostate cancer showed AUCs of 0.79 (95% confidence interval [CI] 0.74-0.84) for the ERSPC-RC3/4, 0.81 (95% CI 0.77-0.86) for the van Leeuwen model, and 0.68 (95% CI 0.63-0.74) for the PBCG-RC, compared to 0.58 (95% CI 0.52-0.65) for prostate-specific antigen alone. The ERSPC-RC3/4 was the best calibrated in the moderate-risk range of 10-40%, whilst the van Leeuwen model was the best calibrated in the low-risk range of 0-10%. The van Leeuwen model demonstrated the greatest net benefit from 10% risk onwards, followed closely by the ERSPC-RC3/4 and then the PBCG-RC. CONCLUSION: The ERPSC-RC3/4 demonstrated good performance and was comparable to the van Leeuwen model with regard to discrimination, calibration and net benefit for an Australian population undergoing TP prostate biopsy. It is one of the most accessible risk calculators with an easy-to-use online platform, therefore, we recommend that Australian urologists use the ERSPC-RC3/4 to predict risk in the clinical setting.

Update on Pheochromocytoma and Paraganglioma from the SSO Endocrine/Head and Neck Disease-Site Work Group. Part 1 of 2: Advances in Pathogenesis and Diagnosis of Pheochromocytoma and Paraganglioma.

This first part of a two-part review of pheochromocytoma and paragangliomas (PPGLs) addresses clinical presentation, diagnosis, management, treatment, and outcomes. In this first part, the epidemiology, prevalence, genetic etiology, clinical presentation, and biochemical and radiologic workup are discussed. In particular, recent advances in the genetics underlying PPGLs and the recommendation for genetic testing of all patients with PPGL are emphasized. Finally, the newer imaging methods for evaluating of PPGLs are discussed and highlighted.

Update on Pheochromocytoma and Paraganglioma from the SSO Endocrine and Head and Neck Disease Site Working Group, Part 2 of 2: Perioperative Management and Outcomes of Pheochromocytoma and Paraganglioma.

This is the second part of a two-part review on pheochromocytoma and paragangliomas (PPGLs). In this part, perioperative management, including preoperative preparation, intraoperative, and postoperative interventions are reviewed. Current data on outcomes following resection are presented, including outcomes after cortical-sparing adrenalectomy for bilateral adrenal disease. In addition, pathological features of malignancy, surveillance considerations, and the management of advanced disease are also discussed.

The Risks and Benefits of Long-term Use of Proton Pump Inhibitors: Expert Review and Best Practice Advice From the American Gastroenterological Association.

BACKGROUND & AIMS: The purpose of this review is to evaluate the risks associated with long-term use of proton pump inhibitors (PPIs), focusing on long-term use of PPIs for three common indications: gastroesophageal reflux disease (GERD), Barrett's esophagus (BE), and non-steroidal anti-inflammatory drug (NSAID) bleeding prophylaxis. METHODS: The recommendations outlined in this review are based on expert opinion and on relevant publications from PubMed, EMbase, and the Cochrane library (through July 2016). To identify relevant ongoing trials, we queried clinicaltrials.gov. To assess the quality of evidence, we used a modified approach based on the GRADE Working Group. The Clinical Practice Updates Committee of the American Gastroenterological Association has reviewed these recommendations. Best Practice Advice 1: Patients with GERD and acid-related complications (ie, erosive esophagitis or peptic stricture) should take a PPI for short-term healing, maintenance of healing, and long-term symptom control. Best Practice Advice 2: Patients with uncomplicated GERD who respond to short-term PPIs should subsequently attempt to stop or reduce them. Patients who cannot reduce PPIs should consider ambulatory esophageal pH/impedance monitoring before committing to lifelong PPIs to help distinguish GERD from a functional syndrome. The best candidates for this strategy may be patients with predominantly atypical symptoms or those who lack an obvious predisposition to GERD (eg, central obesity, large hiatal hernia). Best Practice Advice 3: Patients with Barrett's esophagus and symptomatic GERD should take a long-term PPI. Best Practice Advice 4: Asymptomatic patients with Barrett's esophagus should consider a long-term PPI. Best Practice Advice 5: Patients at high risk for ulcer-related bleeding from NSAIDs should take a PPI if they continue to take NSAIDs. Best Practice Advice 6: The dose of long-term PPIs should be periodically reevaluated so that the lowest effective PPI dose can be prescribed to manage the condition. Best Practice Advice 7: Long-term PPI users should not routinely use probiotics to prevent infection. Best Practice Advice 8: Long-term PPI users should not routinely raise their intake of calcium, vitamin B12, or magnesium beyond the Recommended Dietary Allowance (RDA). Best Practice Advice 9: Long-term PPI users should not routinely screen or monitor bone mineral density, serum creatinine, magnesium, or vitamin B12. Best Practice Advice 10: Specific PPI formulations should not be selected based on potential risks.

Adjuvant and Neoadjuvant Therapy, Treatment for Advanced Disease, and Genetic Considerations for Adrenocortical Carcinoma: An Update from the SSO Endocrine and Head and Neck Disease Site Working Group.

This is the second of a two-part review on adrenocortical carcinoma (ACC) management. While margin-negative resection provides the only potential cure for ACC, recurrence rates remain high. Furthermore, many patients present with locally advanced, unresectable tumors and/or diffuse metastases. As a result, selecting patients for adjuvant therapy and understanding systemic therapy options for advanced ACC is important. Herein, we detail the current literature supporting the use of adjuvant mitotane therapy, consideration of adjuvant radiation therapy, and utility of cytotoxic chemotherapy in patients with advanced disease. Ongoing investigation into molecular targeted agents, immunotherapy, and inhibitors of steroidogenesis for the treatment of ACC are also highlighted. Lastly, the importance of genetic counseling in patients with ACC is addressed as up to 10% of patients will have an identifiable hereditary syndrome.

Evaluation, Staging, and Surgical Management for Adrenocortical Carcinoma: An Update from the SSO Endocrine and Head and Neck Disease Site Working Group.

This is the first of a two-part review on adrenocortical carcinoma (ACC), a rare and aggressive malignancy that often presents at an advanced stage. Most patients present with symptoms related to cortisol and/or androgen excess. Appropriate biochemical evaluation and imaging is important in assessing the extent of disease, operative planning, and oncologic surveillance for patients with ACC. For patients with locoregional disease, potential cure requires margin-negative resection, and accumulating evidence suggests that regional lymphadenectomy should be performed. Although laparoscopic adrenalectomy is reported by some to be adequate for localized ACC, open resection in the hands of an experienced adrenal surgeon is the gold standard for operative management of this disease. Cure is rare following disease relapse, however select patients with severe symptoms related to hormone excess or pain may benefit from resection of local or distant recurrence. For best oncologic outcomes, it is recommended that all patients with ACC be treated at centers with multidisciplinary expertise in management of this rare and aggressive malignancy.

Estimated glomerular filtration rate's time to nadir after robot-assisted partial nephrectomy: Predictors and clinical significance on renal functional recovery.

OBJECTIVES: To investigate the impact of postoperative time to nadir of estimated glomerular filtration rate on renal functional changes after robot-assisted partial nephrectomy. METHODS: From 2006 to 2015, 287 patients with renal mass who underwent robot-assisted partial nephrectomy in a referral center were analyzed. The cohort was evaluated based on their time to develop nadir: group 1 (no nadir), group 2 (<48 h) and group 3 (≥48 h). The outcome measures were to evaluate the renal function recovery between groups, risk factors for development of nadir ≥48 h, as well as predictors of chronic kidney disease upstaging. RESULTS: The mean estimated glomerular filtration rate percentage change was the worst in group 3 compared with groups 1 and 2, with 13.8%, -0.67% and 8%, respectively (P < 0.001). Chronic kidney disease upstaging was more common in group 3 compared with the other groups (P < 0.001). Age, tumor size, PADUA score and warm ischemia time were predictors of developing ≥48 h estimated glomerular filtration rate nadir (odds ratio 1.04, P = 0.002; odds ratio 1.43, P < 0.001; odds ratio 1.24, P = 0.018; odds ratio 1.05, P < 0.001), respectively. The 5-year probability of freedom from chronic kidney disease upstaging was lower in group 3 (75.6%) compared with the other groups - 88.1% and 100% (P = 0.003). Time to nadir ≥48 h was a predictor of chronic kidney disease upstaging (odds ratio 3.02, P = 0.022). CONCLUSIONS: A continuous decline in estimated glomerular filtration rate (≥48 h) after partial nephrectomy is associated with increased risk of poor functional recovery overtime. Age, tumor size, PADUA score and warm ischemia time are independent predictors of developing ≥48 h time to nadir of estimated glomerular filtration rate. This higher risk subgroup should be targeted for stricter follow up to allow early detection of future risk of renal functional decline.

Perioperative and short-term outcomes of Retzius-sparing robot-assisted laparoscopic radical prostatectomy stratified by gland size.

OBJECTIVE: To investigate the effect of preoperative prostate volume (PV) on the perioperative, continence and early oncological outcomes among patients treated with Retzius-sparing robot-assisted laparoscopic radical prostatectomy (RS-RALP). PATIENTS AND METHODS: This is a retrospective analysis of 294 patients with organ-confined prostate cancer treated with RS-RALP in a high-volume centre from November 2012 to February 2015. Patients were divided into three groups based on their transrectal ultrasonography estimated PV as follows: group 1, <40 mL (231 patients); group 2, 40-60 mL (47); group 3, >60 mL (16). Perioperative, oncological, and continence outcomes were compared between the three groups. RESULTS: The median [interquartile range (IQR)] PV for each group was; 26.1 (22-31) mL, 45.9 (41-50) mL, and 70 (68-85) mL. Blood loss was higher in group 3 compared to groups 2 and 1; at a median (IQR) of 475 (312-575) mL, 200 (150-400) mL, and 250 (150-400) mL, respectively (P = 0.001). The intraoperative transfusion rate was higher in group 3 patients (P = 0.004), while the complication rate did not differ (P = 0.05). The console time was slightly higher but was not statistically significant in group 3 compared to groups 2 and 1; at a mean (sd) of 100 (35) min, 92 (34.4) min, and 93 (24.8) min, respectively (P = 0.70). Biochemical recurrence and the continence rate did not differ between the three groups (P = 0.89 and P = 0.25, respectively). CONCLUSION: RS-RALP is oncologically and functionally equivalent for all prostate sizes but technically demanding for larger prostates. We therefore recommend that surgeons initiate their RS-RALP technique with smaller prostates.

Robot-assisted partial nephrectomy confers excellent long-term outcomes for the treatment of complex cystic renal tumors: Median follow up of 58 months.

OBJECTIVES: To analyze long-term outcomes of robot-assisted partial nephrectomy for treatment of complex cystic renal tumors. METHODS: We retrospectively analyzed the data of patients who underwent robot-assisted partial nephrectomy for cystic (n = 32) and solid (n = 263) renal masses at Severance Hospital, Seoul, Korea. The primary outcome was assessment of perioperative safety for cystic tumor. Secondary outcomes were evaluation of long-term oncological and functional results. RESULTS: Patients' clinical and demographic characteristics were similar among both groups. The median follow up of cystic and solid masses were 58 and 46 months, respectively. Cystic masses were more likely to have low Fuhrman grade 1 and 2 (P = 0.03), and shorter operative time (P = 0.04) compared with solid masses. There was no statistically significant difference regarding warm ischemia time, estimated blood loss, trifecta achievement, length of hospital stay, complication rates and renal function preservation (P > 0.05) between groups. In the solid group, 12 patients (4.1%) recurred, and six patients (2%) died from metastatic renal cell carcinoma, whereas the patients in the cystic group did not have any local or distance recurrence, and the survival rates were 100%. The 5-year cancer-free survival (P = 0.77), cancer-specific survival (P = 0.65) and overall survival (P = 0.83) rates were similar between the groups. CONCLUSION: Robot-assisted partial nephrectomy appears to be safe and feasible treatment for complex cystic renal masses. It confers excellent long-term oncological outcomes. Robot-assisted partial nephrectomy should be the treatment of choice for complex cysts whenever feasible.

Screening for Colorectal Cancer and Evolving Issues for Physicians and Patients: A Review.

Importance: Colorectal cancer (CRC) is the second-leading cause of cancer death in the United States. Screening can reduce CRC mortality and incidence, and numerous screening options, although available, complicate informed decision making. This review provides evidence-based tools for primary care physicians to identify patients with higher-than-average-risk and engage patients in informed decision making about CRC screening options. Observations: Recently, the US Preventive Services Task Force recommended any of 8 CRC screening approaches for average-risk individuals, beginning at age 50 years. Only 2 methods have been shown in randomized clinical trials to reduce mortality: fecal occult blood testing and flexible sigmoidoscopy. Of the 8 programs, screenings using the fecal immunochemical test annually and colonoscopy every 10 years are now the most commonly used tests in the United States and among the most effective in reducing CRC mortality as determined by decision models. With the exception of primary screening using colonoscopy, all of the other screening approaches have multiple steps. Adherence to each phase of a multistep program is critical to achieving maximal effectiveness of the screening program. It is likely that each of the recommended programs can reduce CRC mortality, but other key outcomes may differ such as lifetime burden of colonoscopy, complications, patient acceptance, and cost. Decisions about the timing of screening cessation should be individualized. Conclusions and Relevance: CRC screening is effective if patients adhere to the steps in each screening program. There is no evidence that one program is superior to another. Informed decision-making tools are provided to assist patients and clinicians with the goal of improving adherence to effective screening.

Robot-assisted Partial Nephrectomy for Endophytic Tumors.

Robot-assisted partial nephrectomy (RAPN) has gained increasing popularity in the management of renal masses due to its technical feasibility and shorter learning curve with superior perioperative outcomes compared to laparoscopic partial nephrectomy (LPN). Given the cumulation of surgical experience on RAPN, the indication for RAPN has been extended to more challenging, complex cases, such as hilar or endophytic tumors. Renal masses that are completely endophytic can be very challenging to surgeons. These cases are associated with poor recognition of mass extension, higher risk of inadvertent vascular, or pelvicalyceal system injury. As a result, this can lead to potential positive surgical margin, difficulty in performing renorrhaphy as well as higher perioperative complication rates. There is few evidence of oncologic and functional outcomes of RAPN on treating endophytic masses. Therefore, the objective of this review is to critically analyze the current evidence and to provide a summary on the outcomes of RAPN for endophytic renal masses.

Recurrent multinodular goitre and primary hyperparathyroidism due to adenoma arising in a parathyroid autotransplant more than 20 years after near-total thyroidectomy.

The patient is a female in her 60s with a remote history of a near-total thyroidectomy in 1997 for multinodular goitre. At the initial operation, she sustained a left recurrent laryngeal nerve injury. A devascularised parathyroid gland was autotransplanted into the right sternocleidomastoid muscle. She had been off of thyroid hormone for long periods, and her most recent levothyroxine requirement had fallen to only 25 mcg daily. The patient presented more than 20 years after her thyroidectomy with hoarseness, fatigue and dyspnoea. Laboratory studies suggested primary hyperparathyroidism. Imaging demonstrated bilateral pulmonary emboli and bulky thyroid tissue extending into her mediastinum. She underwent a completion thyroidectomy with the removal of a parathyroid adenoma arising in the autotransplanted parathyroid. This case illustrates the possibility of regrowth of benign thyroid tissue after thyroidectomy. In addition, to our knowledge, this is the first case report of a parathyroid adenoma arising from autotransplantation of a normal parathyroid.