The clinical laboratory: a decision maker hub

Objectives We aimed to share a new laboratory model based on laboratory knowledge, meaningful use of information technology, and partnership with clinicians, to lead the appropriate use of laboratory testing and clinical decision making in the diagnosis of as-yet-undiagnosed disease. More specifically, we evaluate the role of eight different opportunistic interventions to diagnose certain asymptomatic disorders, by means of the automatic registration of appropriate laboratory testing according to different scenarios. Methods This is a retrospective longitudinal study to evaluate the impact of laboratory interventions on the diagnosis of different diseases and on patient care, including data from January 2012 to September 2020. Results Overall, the above strategies have so far identified 2063 patients with clinically relevant as-yet-undiagnosed disorders who would have otherwise remained occult, such as for instance, primary hyperparathyroidism, diabetes, and hypomagnesemia. Conclusions We are facing a new laboratory model, a leading laboratory rather than a passive traditional laboratory, not just to intervene in clinical decision-making, but to make the clinical decision, through the identification of patients with occult disease.

Patterns of Nodal Metastases and Predictors of Occult Disease in HPV-Associated Oropharynx Cancer

Objective For human papilloma virus–associated oropharynx squamous cell carcinoma (HPV+ OPSCC), we evaluated the distribution of neck-level lymph node (LN) metastasis, based on postsurgical histopathology, and the incidence of and risk factors for occult LN metastases, as these patterns need clarification for this newer cancer subset. Study Design Retrospective cohort study. Setting National Cancer Database (NCDB). Methods We analyzed 2358 patients in the NCDB with HPV+ OPSCC who underwent neck dissection (ND) from 2010 to 2015. Incidence and distribution of LN metastases were calculated for neck levels I to V. Variables associated with occult LN metastasis were assessed by multivariate logistic regression. Results In therapeutic NDs (n = 1935), the following proportions of positive LNs were found: level I, 9.0% (n = 175); level II, 81.0% (n = 1568); level III, 29.6% (n = 573); level IV, 11.9% (n = 230); and level V, 4.9% (n = 95). In elective NDs (n = 423), occult-positive LNs were found in 35.8% (n = 152), with the following proportions by level: level I, 3.3% (n = 14); level II, 26.9% (n = 114); level III, 8.7% (n = 37); level IV, 4.0% (n = 17); and level V, 0.2% (n = 1). The presence of occult LNs was independently associated with a Charlson-Deyo score of 1 (odds ratio, 2.26; 95% CI, 1.18-4.31; P = .014) and lymphovascular invasion (odds ratio, 5.91; 95% CI, 3.21-11.18; P < .001). Occult LN metastases were not significantly associated with pT classification, primary site, or number of LNs resected. Conclusion For HPV+ OPSCC, occult nodal disease is common. Therapeutic NDs should encompass at least levels II, III, and IV and possibly I, whereas elective NDs could possibly encompass levels II and III. Level of Evidence 4.

Screening Sarcoidosis Patients for Occult Disease

As sarcoidosis may involve any organ, sarcoidosis patients should be evaluated for occult disease. Screening for some organ involvement may not be warranted if it is unlikely to cause symptoms, organ dysfunction, or affect clinical outcome. Even organ involvement that affects clinical outcome does not necessarily require screening if early detection fails to change the patient's quality of life or prognosis. On the other hand, early detection of some forms of sarcoidosis may improve outcomes and survival. This manuscript describes the approach to screening sarcoidosis patients for previously undetected disease. Screening for sarcoidosis should commence with a meticulous medical history and physical examination. Many sarcoidosis patients present with physical signs or symptoms of sarcoidosis that have not been recognized as manifestations of the disease. Detection of sarcoidosis in these instances depends on the clinician's familiarity with the varied clinical presentations of sarcoidosis. In addition, sarcoidosis patients may present with symptoms or signs that are not related to specific organ involvement that have been described as parasarcoidosis syndromes. It is conjectured that parasarcoidosis syndromes result from systemic release of inflammatory mediators from the sarcoidosis granuloma. Certain forms of sarcoidosis may cause permanent and serious problems that can be prevented if they are detected early in the course of their disease. These include (1) ocular involvement that may lead to permanent vision impairment; (2) vitamin D dysregulation that may lead to hypercalcemia, nephrolithiasis, and permanent kidney injury; and (3) cardiac sarcoidosis that may lead to a cardiomyopathy, ventricular arrhythmias, heart block, and sudden death. Screening for these forms of organ involvement requires detailed screening approaches.

Impact of PSMA-targeted imaging with 18F-DCFPyL-PET/CT on clinical management of patients (pts) with biochemically recurrent (BCR) prostate cancer (PCa): Results from a phase III, prospective, multicenter study (CONDOR).

5501 Background: Current imaging modalities are inadequate for localizing and characterizing occult disease in men with BCR PCa, particularly in pts with low PSAs (<2 ng/mL). There is a need for improved diagnostic imaging to better inform treatment planning. 18F-DCFPyL (PyL) is a novel PET imaging agent that binds selectively with high affinity to PSMA, which is overexpressed in PCa cells. Methods: Men ≥18 years- with rising PSA after definitive therapy and negative or equivocal standard of care imaging (e.g., CT/MRI, bone scintigraphy) were enrolled. A single 9 mCi (333 MBq) ± 20% dose of PyL was injected, followed by PET/CT 1-2 hours later. Primary endpoint was correct localization rate (CLR), defined as percentage of pts with a 1:1 correspondence between at least one lesion identified by PyL-PET/CT and the composite standard of truth: pathology, correlative imaging, or PSA response. The trial was successful if the lower bound of the 95% confidence interval (LLCI) for CLR exceeded 20% for two of three independent, blinded central PyL-PET/CT reviewers. The secondary endpoint, impact of PyL-PET/CT on clinical management of pts was based on the treating physician’s documented clinical plans before and after PyL-PET/CT. Results: 208 men (median PSA 0.8 [0.2 - 98.4] ng/mL) underwent PyL PET/CT. The study achieved its primary endpoint: CLR of 84.8% to 87.0% among the three PyL-PET/CT readers; the LLCI for CLR by all three reviewers was >77%. Here we report the clinical impact. Based on local radiology assessment, PSMA-avid lesion(s) were identified in 69.3% (142/208) of pts. 63.9% (131/205) had a change in intended management after PyL-PET/CT, of which 78.6% (103/131) were attributable to positive PyL finding(s) and 21.4% (28/131) to negative PyL scans. Changes included: salvage local therapy to systemic therapy (n=58); observation before initiating therapy (n=49); noncurative systemic therapy to salvage local therapy (n=43); and planned treatment to observation (n=9). PyL was well tolerated with one drug-related SAE (hypersensitivity) and the most common AE being headache (n=4; 1.9%). Conclusions: PSMA-targeted PyL-PET/CT detected and localized occult disease in most men with BCR presenting with negative or equivocal conventional imaging. PyL-PET/CT led to changed management plans in the majority of pts, thus providing evidence that clinicians find PSMA PET imaging useful in men with recurrent or suspected metastatic PCa. Clinical trial information: NCT03739684 .

Merkel Cell Carcinoma: A 28-Year Experience

Objective To evaluate the management and recurrence outcomes of head and neck Merkel cell carcinoma (HN-MCC) at a single institution. Study Design A retrospective review of outcomes in patients with HN-MCC. Setting A tertiary center from May 1990 to December 2018. Subjects and Methods Electronic medical records of patients with HN-MCC were reviewed. Results Sixty cases were included, with 67% (40 of 60) males and a mean age of 73.3 years. Imaging had a moderate sensitivity and specificity for detection of occult disease when compared with histopathologic analysis. Forty-two percent (25 of 60) of patients underwent neck dissection, and 12% (7 of 60) had a sentinel lymph node biopsy (SLNB). There was a high rate of negative SLNB findings. The majority of patients were treated with surgery alone (29 of 60), followed by a cohort (21 of 60) treated with surgery plus adjuvant treatment, and 10 of 60 patients were treated with radiation therapy with or without chemotherapy. Recurrence-free survival was 50%, 45%, and 42% at 1, 2, and 5 years. Conclusions We report higher recurrence rates and higher negative SLNB result rates than other studies. Our results affirm that imaging may not be a substitute for SLNB and that it had an intermediate ability to identify the occult disease. Traditional predictors, including SLNB and cervical node pathology, may not identify patients at risk for recurrence in HN-MCC. We report similar recurrence rates in patients who had treatment of the cervical nodes by radiation therapy or neck dissection as compared with those who did not receive neck treatment.

The SENIORLAB study in the quest for healthy elderly patients

Reference intervals (RIs) for laboratory analyses by and large, are provided by analytical platform providers – the provenience and preanalytics of materials for the calculation of intervals often remain arcane particularly relating to the age group of donors. In an observational, prospective cohort study on 1467 healthy uniracial Caucasian residents >60 years of age, 105 frequently used lab tests were done on one blood sample. With a nonrestrictive definition of health, several pathological lab results pointing to occult disease have been found and published from SENIORLAB so far. The RIs found for hemoglobin in women went from 117.9 to 152.4 g/L (80–84 years) and in men from 124.9 to 170.6 g/L (90% confidence interval [CI]). This article lists RIs computed with SENIORLAB data for such frequently ordered analyses as platelet counts, vitamin B12 and folate, ferritin and analytes measured to estimate metabolic performance in glucose turnover. In fact, 64.5% of the cohort showed prediabetic fasting plasma glucose (FPG) and/or glycated hemoglobin (HbA1c); total serum folate levels but not red blood cell folate decreased with progressing age. As much as 66% of evaluable study participants had insufficient levels of 25(OH) vitamin D. Published reports from SENIORLAB are referenced in this article.

Reverse Deployment of the Gore Excluder Contralateral Iliac Limbs for Central Venous Occlusive Disease

Central venous occlusive disease is a common finding, especially in the dialysis population. The incidence of central venous occlusions is increasing, largely because of the expanded use of central venous catheters and pacer wires in the growing dialysis population. The clinical sequelae of central venous occlusions are highly variable and depend on the site of occlusion, the presence of collaterals, and the presence of an arteriovenous (AV) fistula on the affected side. Many patients have occult disease, but often the disease presents with failure of the AV access and swelling of the involved extremity, breast, neck, and face. Rarely, a pleural effusion may be present. This chapter discusses the use of Gore Excluder iliac limbs for some large central venous occlusions.