A 69 year old male presented to the hospital due to worsening back pain and lower extremity weakness. He had a medical history of follicular thyroid cancer and underwent lobectomy back in 2016. After admission, patient was found to have multiple metastasis of follicular thyroid cancer with lesion in the lumber spine, and his serum thyroglobulin level was elevated at 1,500 ng/mL (1.3 – 31.8 ng/mL) without thyroglobulin antibody detected. Patient did not present hyperthyroidism symptoms. TSH and total T4 were normal, and free T4 was slightly decreased. During hospitalization, patient was prescribed with Amiodarone, to control atrial fibrillation. Amiodarone is an antiarrhythmic drug used for severe ventricular arrhythmias, paroxysmal atrial tachycardia, and atrial fibrillation. It has high content of iodine and a direct toxic effect on thyroid gland, resulting in thyroid dysfunction in 3-5% of patients. In this case, severe hyperthyroidism was observed after amiodarone administration.
Patient’s FT4 level significantly elevated to >5.2 ng/dL (0.9-1.7ng/dL), total T4 was increased to 21.8 ug/dL (4.5-11.7 ug/dL), and TSH was suppressed to below the detection limit. The sudden increase of FT4 suggested Amiodarone induced thyrotoxicosis (AIT). High content of iodine in Amiodarone could raise blood iodine concentration up to 40 folds and enhance thyroid hormone biosynthesis in thyroid cells. This is the main cause of type 1 AIT, which is more common in patients with underlying thyroid diseases, such as Graves’ disease, or autonomous nodular goiter. Type 2 AIT typically happens in patients without underlying thyroid diseases and is caused by a direct toxic effect of amiodarone on thyroid follicular cells. Pre-formed T4 and T3 in thyroid cells are released into the circulation due to destructive thyroiditis in type 2 AIT. Differentiating these two types is important because it has therapeutic implications. However, the distinction may be difficult because patients may have a mixture of both mechanisms. Thyroid function tests are usually not helpful in the differentiation, but ultrasonography and thyroid scan with iodine uptake can help differentiate type 1 from type 2 AIT.
In this case, thyroid scan with technetium showed reduced thyroid uptake in thyroid lobe, and mild uptake within metastatic lesions, suggesting possible thyroiditis due to amiodarone. Type 2 AIT develops as an inflammatory process and anti-inflammatory glucocorticoids are used in the treatment. Amiodarone was discontinued in this patient and his thyroid function tests indicated improvement of thyroid dysfunction. Amiodarone and its metabolites have a long half-life and accumulate in adipose tissues due to its lipophilic property. Therefore, in some cases, amiodarone toxicity effect can last for months, even after drug withdrawal. To be noted, amiodarone can also induce hypothyroidism, especially in patients with underlying Hashimoto’s thyroiditis or positive antithyroid antibodies.
-Xin Yi, PhD, DABCC, FACB, is a board-certified clinical chemist, currently serving as the Co-director of Clinical Chemistry at Houston Methodist Hospital in Houston, TX and an Assistant Professor of Clinical Pathology and Laboratory Medicine at Weill Cornell Medical College.
2020 has come to an end. I think we can all agree that it’s been a year like no other! It would be an understatement to say that 2020 has been merely “different.” In the lab, we have seen new things, had new challenges, and, despite the craziness of it all, have learned a few things along the way.
I think the word of the year in our lab and many others for 2020 would be “adaption.” We’ve had to adapt, change our thoughts and processes and be more creative. In the spring, in the first wave of COVID, many labs were struggling with procuring, validating, and performing new COVID tests. With the influx of cases and patients, particularly in some hard hit areas, lab staff were overwhelmed with an unprecedented increase in workload. In the hospital where I work, early on we had very few cases and the lab was impacted in the opposite extreme. With canceled elective surgeries and a huge drop in outpatient work, we found ourselves being asked to take flex time. Workload was down and techs were taking time off to help the lab and hospital adjust to the decreased revenue and to say within budget. Things were pretty slow and calm.
When surgeries resumed and physician offices opened back up, things were busier than ever. Everyone seemed to be coming in for lab work that had been pushed aside for months. In addition to an increased volume in our existing tests, we were bringing on new COVID tests. Procedures had to be written and signed off, validations had to be done and everyone needed to be trained on the new tests. We found ourselves faced with supply issues for the new tests and had to do some juggling acts to get new testing onboard. At the same time, we also had to deal with a lot of other “supply” issues. While the hospital as a whole has done very well to manage PPE distribution, the lab has had to get creative, reaching out to new suppliers for cleaning supplies, lab coats and gloves. Lab coats became and still are very difficult to keep in supply. We’ve gone colorful! We used to have blue gloves and purple lab coats, but now have multi colored gloves and lab coats all over the lab from multiple vendors.
Possibly the worst of our supply issues has been the lack of trained technologists. In a profession that is graduating fewer and fewer new techs, and as our work force is getting older, we have been experiencing a shortage of qualified Medical laboratory Scientists and Technicians across the country for a number of years. This past year, with the current pandemic, we have seen techs who were working way past retirement age decide to finally retire, and others taking early retirement. In the past 5 years I have worked in 2 hospitals that have continuously had revolving open positions. In 2020, om a large number of COVID cases amongst lab staff, but have had a few. We have had many more staff out on quarantine for 2 weeks at a time for exposures, sometimes several at a time. And, after waiting for months with elective surgeries on hold, the minute these were again allowed, we have had several staff on simultaneous leaves of absence for surgeries.
How have we compensated and adapted for these shortages and changes? At a time when visitors have been restricted in the hospital, we have found ourselves with a severe shortage of staff. We are also competing with other hospitals in the area in the same situations so are having a hard time hiring and keeping new employees. We have adapted by conducting Zoom interviews for hiring. We are in the middle of a big chemistry project bringing on new instruments and some of this training has also moved to virtual venues. ASCP and other organizations have held totally virtual conferences and symposiums. But, having been forced to implement these new technologies, we have learned new skills that can be used in the future to broaden our outreach and educational opportunities.
It has been a challenge to train new techs and to simply get the daily work done with ongoing staff shortages. Staffing has been at critical levels. We’ve been resilient. We’ve been creative. We have had to implement an On Call list to help fill critical holes in the schedule. This is not popular, and is still a work in progress, but has helped us to think of other ways to solve the problem at hand. Bonuses for working extra shifts have helped. We have relied on our great technologists to fill in extra shifts. I’m very proud of everyone working together. Team work is helping hold us together and get through this very difficult year!
I think If I had to find any “good” about this pandemic, I’d have to say it’s been the lack of commuter traffic, and the fact that all this talk about COVID testing has shone a little light on our profession. Yet, with all the talk of “testing,” even though the general public has some concept of lab testing, they still know very little about the profession and the people doing these tests. They may recognize the terms PCR, and antigen and antibody but we’re still a hidden profession. What can we all do? Talk about the profession in your community. Community groups, high schools and community colleges often welcome speakers, and now you can even do it online! You’ve all heard people talking about antigens and antibodies and PCR, but you can tell them about the profession and the people who work with these tests every day. It would be very hopeful to say that this pandemic could highlight the Medical Laboratory profession to the point where students would be filling our programs and we’d see a new interest in the field.
Did we ever think this would last this long? in the spring, making hundreds of masks, I thought making holiday masks would be fun. But then I thought to myself, “ I won’t need to make Halloween masks or Christmas masks.” I never thought we’d still be wearing masks at New Year’s! But masks have become so normal that we have even gotten used to them. I took a cold walk a couple days ago and thanked the mask for keeping my face warm!
2020 has had many ups and downs, many challenges. I am proud to say that Medical laboratory professionals have lived up to those challenges and we can and should feel good about our accomplishments and contributions to fighting this pandemic. We’ve been resilient, we’ve adapted and we’ve grown. We’re on a roller coaster ride but we’re still holding on. Hold on tight and wear that mask!
-Becky Socha, MS, MLS(ASCP)CM BB CM graduated from Merrimack College in N. Andover, Massachusetts with a BS in Medical Technology and completed her MS in Clinical Laboratory Sciences at the University of Massachusetts, Lowell. She has worked as a Medical Technologist for over 30 years. She’s worked in all areas of the clinical laboratory, but has a special interest in Hematology and Blood Banking. When she’s not busy being a mad scientist, she can be found outside riding her bicycle.
In part 1, we reviewed Michael Porter’s Value Chain and looked at inbound logistics for pathology. Now we will turn to operations, or the production of diagnostic results.
In the United States, almost all cancer diagnosis and care are in the private sector. There are very few examples of diagnostic services that are provided for free. Because laboratories derive revenue from every specimen for the most part, there is a natural desire to increase the volume in the laboratory from management because volume equals revenue. Pathology also has inherent economy of scope and scale such that a basic system that could process 1 case per day for an operating cost of $500,000 per year, could process 200 cases per day for a cost of $4,000,000 per year (a 200-fold increase in volume with only a 8-fold increase in cost). It is important to note in this comparison that in the former, the cost per case is $2000 while in the latter it is $80 (a 25-fold difference). When we consider an allocated or operating budget to run a pathology diagnostic laboratory where revenue is not reflected to laboratory management, this desire to increase volume is lacking directly by laboratory staff (more work but no additional funding) but still may be desired by higher level administration for revenues that pay for other aspects of the system (cross-subsidization). Consider a laboratory that is asked to process 25,000 samples per year, has 6 support staff and 3 pathologists. This would equate to each pathologist signing out ~50 cases per day on average, Monday – Friday, with four weeks of vacation annually. If those pathologists are the direct recipients of the profits of the laboratory, such a high case sign-out rate may be acceptable. If they only receive their allotted salary with no potential for profit sharing, they are unlikely to maintain such a high rate of production. Moreover, they will likely demand higher salary and/or additional staff and will do so much more quickly as volumes increase than would pathologists who share in profits. When we transfer this concept to a public low-resourced laboratory setting in a low- and/or middle-income country where government salaries are lower, there are far fewer skilled personnel, and budgets are smaller, there is essentially no incentive for public/government-funded laboratories to increase volume because it results in more work for the existing staff with no benefit. Yet, with the small volumes we see in LMICs currently, their costs per case are much higher than in HICs. When we turn our lens to the patient and that patient’s maximum value, the profit-sharing model is likely to yield the shortest turnaround time for a given patient. There is a trade-off in this scenario between speed of results and amount of communication/coordination between the clinician and the pathologist. Allocated budgets and public laboratories may produce slower results that are of the same technical quality and, in academic settings, may include additional communication/coordination with clinical teams. Standards exist for a maximum turnaround time goal (i.e., for the College of American Pathologists, it is 3 days). Without external regulation and accreditation, laboratories may fail to provide value to the patient by delaying diagnoses until they essentially are useless. Turnaround times in LMICs may be considered “very good” at 2-weeks, a timepoint that would not be sustainable for HICs laboratories.
Operations – This activity “includes procedures for converting raw materials into a finished product or service”. For the lens of maximum value to the patient, from the moment a biopsy is received in the laboratory to the moment a final report is generated should be minimized and the report itself should adhere to quality standards internally and externally. Once all reagents and supplies are obtained and specimens are received, the operations process can be engaged which includes grossing, processing, embedding, microtomy, staining, special stains, immunohistochemistry, case professional review, and report production. In each step of this stepwise process, specific skilled personnel are needed, matched with specific reagents and supplies to complete the step. Laboratory efficiency and product quality can be dually achieved with highly trained personnel, functioning, well-maintained equipment, optimized workflow, continuous communication and data collection, and highly skilled management to control the process wholly and in parts. One of the challenges for HIC pathology laboratories or health systems are large resections (i.e., mastectomies, colectomies, etc.) and autopsies. The former is integral to cancer care for mid-stage cancers to inform margins and guide treatment; however, they require more personnel time to gross, process, and read, more physical resources to dissect and sample, and may have a series of challenges related to “what’s left in the bucket?” that do not occur when a small biopsy is entirely submitted (although standardization of grossing and reporting can often ameliorate this issue). For the latter (i.e., autopsies), the costs of these procedures are extremely high across the board and there is, to date, no reimbursement or payment for this final procedure in a patient’s medical journey. The value of the autopsy has been explained elsewhere but such value to healthcare systems and to individual and groups of patients is often not delineated enough to make these services a priority, unfortunately. Stepping back from operations, what is commonplace in HICs is that large academic center pathology laboratories most often associated with comprehensive cancer centers are evaluating major cancer surgery specimens as well as autopsies while their private practice and community hospitals focus on small biopsies. There are certainly private practice and community hospitals that evaluate large specimens, but they do so in the context of large biopsy volumes (i.e., cross-subsidization). Tertiary care center pathology laboratories receive referrals (secondary review of biopsies) and surgical samples without the large volumes of primary biopsies to provide off setting revenue. Without high volumes of biopsies to subsidize the costs of large resections, value chain for laboratories becomes quickly degraded and laboratories may even become cost centers, especially if complex immunohistochemical works ups are considered. For patients, care at academic centers and comprehensive cancer centers is viewed as superior with access to clinical trials, multidisciplinary teams, advanced technology, and highly complex diagnosis of rare entities; however, the bulk of pathology services provided, being standardized, are essentially task-shifted from for-profit high volume laboratories that could subsidize the costs to large health systems that cost more to run often without the benefit of the primary diagnostic biopsy material revenue flow.
It is quite easy to see how this part of the value chain can fail in an LMIC because pathology operations are large, complex, and interlocking. For example, if the single embedding center goes offline, manual processes, which are slower and produce poorer quality blocks must be used and efficiency is lost. If the tissue processor goes offline, the entire process is stopped until it is restarted. If there is one pathologist and they go on vacation or immigrate to another country offering better salary, the process is stopped indefinitely. As mentioned above, for a laboratory with a low volume and limited staff, increases in volume are a considered negative because incentivization is lacking. Because these laboratories are often the “only game in town”, they must deal with small biopsies, large resections, and autopsies but without the revenue streams seen in HICs to offset costs or create cross-subsidization (i.e., reimbursement, private pay, etc). This is due to limited access for patients and biopsy rates for the population that may be less than 20% (i.e., of all people that NEED a biopsy, less than 20% receive a biopsy due to access issues). There is a great need to achieve balance in this problem between the minimal volume a lab should process and adequate compensation for laboratory staff to achieve this volume. Modelling and projections expected for a given population can be used to inform governments and market makers about what number of services are needed and, subsequently, public-private partnerships become a primary tool to achieve the balance. For individual gaps such as lack of staff, the value of the operations can be improved with training, telepathology support, visiting pathologists, and management training and improve the overall value improved for the patient.
To summarize this piece, operations for diagnostic pathology has an inherent economy of scope and scale such that an optimal case mix exists which creates maximum value for the patient—shortest turnaround time with most accurate results—and creates a sustainable revenue stream for the laboratory operations (mix of biopsies and resections). Competitive advantage is complex in this space because speed and volume are contrasted with specimen complexity, all of which should be performed through a standard of care.
In the next part, we will look at outbound logistics or the outgoing report to the clinical team.
References
Porter, M. (1985). The value chain and competitive advantage, Chapter 2 in Competitive Advantage: Creating and Sustaining Superior Performance. Free Press, New York, 33-61.
-Dan Milner, MD, MSc, spent 10 years at Harvard where he taught pathology, microbiology, and infectious disease. He began working in Africa in 1997 as a medical student and has built an international reputation as an expert in cerebral malaria. In his current role as Chief Medical officer of ASCP, he leads all PEPFAR activities as well as the Partners for Cancer Diagnosis and Treatment in Africa Initiative.
Lablogatory 