2022 Southern Medical Research Conference - Journal of Investigative Medicine
Thursday, February 10, 2022
#178 Evaluation of quality of life data reporting in metastatic kidney cancer trials
FG Bell*
JC Henegan
University of Mississippi, University of Mississippi, University Park, MS, US, Jackson, MS
Purpose of Study
Health related quality of life (HRQoL) results provide information as to the general impact on a patient's life that a therapy may have. Both statistical and clinical significance should be reported for HRQoL but not all studies present both pieces of information.
We sought to identify if there is a difference in the frequency of the presentation of statistical significance of HRQoL versus clinical significance of HRQoL in phase III studies of investigational agents in metastatic renal cell carcinoma reporting longitudinal results of overall HRQoL.
Methods Used
A Medline search using the MESH term 'Kidney Neoplasms' and filtering for Phase III clinical trials was conducted. The articles were reviewed and those studies which included longitudinal results of overall HRQoL in phase III studies of investigational agents in metastatic renal cell carcinoma were included in the analysis. The binomial test was used to calculate a z-score, with the frequency of the reporting of statistical significance used as the expected probability of reporting of clinical significance.
Summary of Results
31 phase III trials were able to be included in the analysis. Of these, 26 (83%) reported if a result was statistically significant and 21 (68%) reported if a result was clinically significant. Due to the small sample size the data did not meet the requirements for a z-test.
Conclusions
There is a nominal increase in the frequency of the presentation of statistical significance of HRQoL versus clinical significance of HRQoL in phase III studies of investigational agents in metastatic renal cell carcinoma reporting longitudinal results of overall HRQoL. However, the small sample size prevented the planned statistical analysis from being able to be reliably performed.
#179 Cardiomyopathy after doxorubicin
C Bergeron*
A Garcia
LSU Health New Orleans, New Orleans, LA
Purpose of Study
To highlight the importance of a thorough work-up for new onset heart failure in patients treated with doxorubicin
Methods Used
Review of Electronic Health Records and literature review
Summary of Results
A 59-year-old female with PMH of hypertension was diagnosed with left breast cancer. She underwent a modified radical mastectomy and pathology showed a stage III breast cancer. Transthoracic echocardiogram (ECHO) showed left ventricular (LV) hypertrophy with normal cardiac function (left ventricular ejection fraction, LVEF > 55%). Electrocardiogram (ECG) showed LV hypertrophy and no additional abnormalities. She started adjuvant chemotherapy with dose-dense doxorubicin (D), cyclophosphamide, and paclitaxel. Cumulative dose of D was 240 mg/m2. Two months after completing D, she presented with tachycardia. She reported 5 months of progressive dyspnea since beginning chemotherapy, followed by an acute worsening of dyspnea 2 weeks prior to presentation.
At presentation, brain natriuretic peptide was elevated. CXR showed signs of volume overload. ECG showed anteroseptal infarct of undetermined age. ECHO showed a LVEF of 25–30%. The patient was diagnosed with new onset heart failure (HF) with reduced ejection fraction (HFrEF) secondary to doxorubicin cardiomyopathy (DCMP). Following stabilization, she was discharged on goal-directed medical therapy for HFrEF and referred for follow-up with cardiology. At follow-up, nuclear stress testing revealed a large mid-distal defect in the anteroseptal wall corresponding to left anterior descending artery (LAD) territory infarction. Left heart catheterization and coronary angiography showed 100% occlusion of the LAD and 80% of the left circumflex artery, suggesting ischemic cardiomyopathy as the true cause of this patient's new onset HFrEF.*
DCMP is a well-described cause of dilated cardiomyopathy. Dilated cardiomyopathy is defined by ventricular dilatation with systolic dysfunction, in the absence of coronary artery disease, hypertension, valvular disease, or congenital heart disease. The absence of these conditions is required for the diagnosis of dilated cardiomyopathy and subsequently DCMP. Risk factors for DCMP include age (> 65 years), female gender, preexisting cardiovascular disorders, hypertension, smoking, obesity, diabetes and high cumulative dose. It is usually classified as acute (occurs during treatment), subacute (detected within 1 year) and chronic (detected years after exposure). The prognosis of DCMP is poor and therefore it is essential to rule out treatable causes of HFrEF.
Conclusions
Cardiomyopathy is a well described, but uncommon side effect of D. Symptomatic HF is seen in approximately 1% of patients. Our patient had several risk factors for DCMP. This case highlights the importance of thorough evaluation for the cause of newly diagnosed HF even when the etiology seems straightforward. While D is a well described caused of dilated cardiomyopathy, ruling out more common causes of LV dysfunction are necessary to make the diagnosis.
#180 Leukemia cutis: an uncommon presentation of acute myeloid leukemia
D Beyer*
M Lieux
B Van Court
C Pham
C Van Dreumel
DA Van
SM Ford
R Foret
LS Engel
S Sanne
LSU Health New Orleans, New Orleans, LA
Case Report
Introduction
Leukemia Cutis is a rare condition characterized by infiltration of neoplastic cells into the epidermis and dermis with a characteristic dermatologic appearance. Leukemia cutis generally portends a poor prognosis in the setting of newly diagnosed blood cancers.
Case
A 31-year-old man without past medical history presented after 1 month of progressive dyspnea on exertion, worsening fevers, thirty pound unintentional weight loss and diffuse rash on all extremities and trunk. Physical exam was significant for fever, tachycardia and scattered petechia and erythematous papules and macules on his bilateral upper and lower extremities. Initial laboratory findings were significant for leukocytosis (222,000) with 94% immature mononuclear cells and thrombocytopenia (8,000). Punch biopsy was performed and pathology returned leukemia cutis with myeloid features. Bone marrow biopsy was significant for acute myeloid leukemia with 86% large blastoid cells. Patient was started on induction chemotherapy with cytarabine and idarubicin resulting in slow resolution of rash.
Discussion
Leukemia cutis is a challenging diagnosis and rare presentation of leukemia. When coupled with a new diagnosis of acute myeloid leukemia, as in this patient, portends a worse prognosis. This patient presented in blast crisis with cutaneous involvement and new diagnosis of acute myeloid leukemia was made promptly based on bone marrow biopsy results. Prompt dermatologic consultation resulted in diagnosis of leukemia cutis based on punch biopsy. After initiation of induction chemotherapy (cytarabine and idarubicin), his cutaneous lesions subsided significantly.
#181 Cobalamin deficiency masquerading as possible thrombotic microangiopathy
L Bradley*
E LeJeune
The University of Mississippi Medical Center, Jackson, MS
Case Report
Prompt recognition of Thrombotic Thrombocytopenic Purpura (TTP) is of utmost importance for clinicians considering the near 100% mortality rate associated with delayed treatment. Cobalamin (B12) deficiency is a rare cause of hemolytic anemia and can sometimes mimic the presentation of TTP. Though an infrequent diagnosis, pseudo-thrombotic microangiopathy (TMA) can in some cases result in inappropriate treatment with plasmapheresis if not distinguished from true TTP early. Here we present a case of severe B12 deficiency causing a TMA like syndrome.
58 year old African American male presented to the emergency department complaining of shortness of breath. His laboratory values were discovered to be white blood cell count 9.89 TH/cmm with normal differential, hemoglobin 5.7 g/dL, hematocrit 18.1%, platelet count 75,000 TH/cmm. He was admitted to the internal medicine service for further evaluation. Further workup revealed MCV of 127 fl, LDH >3500 U/L, Haptoglobin <10, and Total bilirubin of 2.22 mg/dL with indirect bilirubin 1.80 mg/dL. Reticulocyte count 1.2%. Direct antibody coombs test was negative. Serum B12 level was 150 with Methylmalonic acid of 5.52umol/mmol. On peripheral blood smear 1–3 schistocytes per high power field, rare tear drop cells, and numerous hypersegmented neutrophils were observed. ADAMTS-13 activity level was 78%.
Plasmapheresis was held and B12 1000 mcg IM was given daily for 7 days, then weekly for 4 weeks, followed by monthly indefinitely. On hospital follow up 6 weeks later patient had complete resolution of his anemia and thrombocytopenia. Serum B12 level was >500. He was referred to gastroenterology for further evaluation of suspected B12 malabsorption etiology.
Though rare, B12 deficiency causing hemolytic anemia is a known disease process and should be considered in the differential for hemolytic anemia. The pathogenesis of low B12 causing hemolytic anemia is uncertain but it has been demonstrated in vitro that elevated levels of homocysteine can lead to endothelial damage likely resulting in hemolysis. Early recognition of this patient's pseudo-TMA likely shortened his hospital stay and prevented unnecessary initiation of plasmapheresis.
#182 Correlation between intubation and palliative care: what is the trend?
OH Brunson*
The University of Mississippi Medical Center, Jackson, MS
Purpose of Study
Over the last twenty years there has been an increase in the number of endotracheal intubations.1 In that same time period, palliative care has emerged with a focus on quality of life and alleviating suffering in patients with chronic, severe illness. More recently societal guidelines, including the American Society of Clinical Oncology, have recommended early integration of palliative care. 2,3 Hypothetically, earlier goals of care discussions could lead to less invasive interventions, such as intubation. With this focus on earlier intervention, we aim to study the correlation between inpatient palliative care consultation and intubations at our institution.
Methods Used
Utilizing a function of EPIC electronic medical record SlicerDicer, we were able to identify patients admitted to the University of Mississippi Medical Center with a co-occurrence of intubation and palliative care consult, examine patient demographics and calculate relative risk (RR).
Summary of Results
We first looked at intubations, which increased by 136% from 2012–2016 with the rate of change from 2017–2020 varying by only 1–2% a year. Next, we looked at palliative care consults. Since inpatient palliative care became available in 2017, the number of consults increased by 39% (264 to 367). We then analyzed 99,622 admissions from 2017–2020 to look for co-occurrences of intubation and palliative care consultation during the same admission. In the general population, excluding patients with a cancer diagnosis, co-occurrences increased by 86% from 2017–2020 (23 to 43). In cancer patients, co-occurrences increased initially by 600% from 2017–2019 (2 to 14), but then decreased by 35% in 2020. Based on this data, the RR of intubation and a palliative care consult during an admission was higher in non-cancer patients than cancer patients (RR 5.8, RR 2.3 respectively). The highest RR was seen in non-cancer patients less than 30 and 50–70 years old (RR 13.6, RR 7.8 respectively).
Conclusions
Overall, there was an increase in co-occurrences of intubation and palliative care consultation. This could be attributed to a growing palliative care service, but the excess RR in younger, non-cancer patients may point to the palliative care team being increasingly utilized in the acute, critically ill patient. Notably, co-occurrences in non-cancer patients increased compared to cancer patients in 2020, likely due to Sars-Cov2. Though co-occurrences increased in cancer patients overall, the decreased RR compared to non-cancer patients is promising. This could point to more sub-specialist involvement in inpatient palliative discussions and/or earlier goals of care discussions. There is still work to be done to emphasize earlier goals of care discussions in chronic illnesses, which could ultimately lead to a decrease in the number of co-occurrences of intubation and palliative care over time. Further investigation is needed to follow this trend.
#183 Diagnostic dilemma: primary orbital squamous cell carcinoma or not?
VK Carey1*
J Steyer1
P Goel1
A Ananthula1
SK Halat2
R Walvekar1
R Chowdry1
1LSU Health New Orleans, New Orleans, LA
2Tulane University School of Medicine, New Orleans, LA
Introduction
Primary orbital squamous cell carcinoma (SCC) is extremely rare with only 9 cases reported in literature. Secondary squamous cell carcinoma of the orbit is more common, accounting for 6.8% of orbital tumors and is usually the result of local invasion from a cutaneous primary (eyelid, conjunctiva, lacrimal gland, sino-nasal tract etc.), perineural invasion or distant metastasis. Here, we present a case of SCC of the right orbit which poses a diagnostic challenge as to the origin of the tumor and optimal management strategy.
Case
The patient is a 60-year-old male with a history of right eye injury and subsequent blindness who presented with a large right orbital mass which has been growing for a few months. The patient was struck in his right eye with metal debris several decades ago. Biopsy confirmed a diagnosis of moderately differentiated squamous cell carcinoma. Within a month of presentation, the mass continued to further grow rapidly with involvement of the entirety of the right orbit with proptosis. Ulceration along the medial canthus were noted with intermittent mild bleeding. The patient was unable to move his eyelids. CT of the orbits demonstrated a large right orbital mass extending into orbital apex with intraconal & extraconal involvement extending into the supraorbital & infraorbital fissures. The globes & optic nerve were not identified. MRI of the brain was negative for intracranial involvement. CT Chest, Abdomen, Pelvis was negative for any distant metastasis. Decision was made to proceed with right orbital exenteration, parotidectomy, modified radical neck dissection, and free flap reconstruction. Histopathology showed a 6.1 cm invasive squamous cell carcinoma with tumor invasion into the globe, extraocular muscles, orbital fat and optic nerve. Lymphovascular and perineural invasion was present. All margins were negative for malignancy. He is staged as pT4aN0M0 SCC of the right orbit. He has tolerated surgery well and plan is to start adjuvant chemo-radiation with weekly cisplatin given the risk of recurrence in his case.
Discussion
The orbit does not contain squamous epithelium, which accounts for the rarity of the disease. Case reports have detailed primary orbital SCC from dermoid cysts, lacrimal gland cysts with squamous metaplasia and conjunctival cysts occurring after ocular surgery. Squamous metaplasia is a consideration in this patient secondary to chronic irritation from his eye injury. In further review of existing literature, we inferred that we might not be able to confirm where the SCC originated in such cases with de novo orbital mass. Orbital SCC is usually treated with surgery with radiotherapy or chemoradiation depending on the extent of tumor invasion and risk of recurrence.
#184 Primary pulmonary melanoma presenting as brain metastasis
KJ Clay1*
BS Ross2
F Joiner1,2
1The University of Mississippi Medical Center, Jackson, MS
2G.V. (Sonny) Montgomery VA Medical Center, Jackson, MS
Case Report
Melanoma, a malignant tumor of pigment-producing cells, is a potentially fatal neoplasm most commonly arising from a cutaneous origin. However, cases arising from mucosal, ocular, and visceral sites are described. Here, we report a case of a primary melanoma of the lung with pulmonary and brain metastases.
A 42-year-old male with diabetes mellitus and a tobacco use disorder presented to the emergency department after a five-minute episode of aphasia associated with perioral tingling. Upon arrival, he was able to speak clearly, and he had no focal neurologic deficits. The remainder of his review of symptoms and physical exam was unremarkable. The differential diagnosis included seizure or transient ischemic attack. A non-contrast head CT revealed an acute focal hemorrhage within the left parietal lobe with a small subarachnoid component. MRI imaging further demonstrated a 1.5 cm rim-enhancing mass concerning for hemorrhagic metastasis. He was admitted. An awake craniotomy with tumor resection revealed a high-grade malignant neoplasm positive for MART1 and SOX10 and negative for GFAP, TTF-1, CK7, CK20, EMA, and CD34, which favored metastatic melanoma. This lesion was BRAF V600E positive and NRAS negative. Subsequent PET scanning revealed multiple FDG-avid pulmonary nodules, with an endob ronchial mass amenable to biopsy. Bronchoscopic biopsy of this mass demonstrated malignant cells positive for MART1 and SOX10 consistent with malignant melanoma and suggested that this was the primary lesion. A specialty-conducted dermatologic evaluation failed to reveal other potential primary sites. Initial therapy consisted of gamma knife radiation to the post-resection brain tumor bed and immunotherapy with nivolumab and ipilimumab. Two months later, an MRI showed multiple new intracranial metastases, and a PET scan showed an increase in the size of the endobronchial lesion and an increase in the number and size of the metastatic lung nodules. The patient has completed four cycles of nivolumab/ipilimumab and is being evaluated for dabrafenib/trametinib combination therapy.
Primary malignant melanoma of the lung is rare, accounting for 0.01% of all lung neoplasms. Though the pathogenesis of these tumors remains obscure, it is believed that primitive melanoblasts may migrate to the viscera during embryogenesis. New therapies have emerged for metastatic cutaneous melanoma that target specific kinases and protein receptors such as PD-1, CTLA-4, BRAF, and MEK. However, there is a paucity of data on the efficacy and safety of these treatments with non-cutaneous metastatic melanoma. This case illustrates the diagnostic and therapeutic challenges associated with this rare pathological entity.
#185 Stage ii endometrial carcinoma with false positive para-aortic lymphadenopathy: the importance of pretest probability
JA Cooper*
A Garcia
LSU Health New Orleans, New Orleans, LA
Purpose
Case report to increase awareness of pretest probability in the presence of abnormal imaging findings
Methods
Review of Electronic Health Records and literature review
Results
This patient is a 61-year-old female with a history of intermittent vaginal spotting since her early 50's. On physical exam, normal vaginal atrophy was observed, and bi-manual recto-vaginal exam showed normal-sized uterus without adnexal masses or nodularity. A Pap-smear with dilation and curettage revealed endometrial carcinoma, endometrioid type with squamous differentiation. Hysterectomy with bilateral salpingo-oophorectomy, bilateral pelvic sentinel biopsy, and bilateral pelvic lymphadenectomy was performed. Pathology showed a grade 1 endometrioid carcinoma with greater than 50% myometrial invasion. The cervical stroma contained a 2 mm focus of tumor, and all 18 pelvic lymph nodes were negative meriting a diagnosis of Stage II endometrial carcinoma. Vaginal cuff brachytherapy, a non-morbid treatment, was offered as adjuvant therapy.
Staging PET/CT scan showed a hypermetabolic left para-aortic lymph node at the renal level suspicious for active neoplastic disease. Based on this the recommendation for adjuvant treatment was changed to extended field radiation and systemic chemotherapy, a treatment associated with significantly more toxicity. However, it was discussed that this was an unusual presentation and further evaluation was required. A CT-guided biopsy of the left para-aortic lymph node was performed and showed no malignant cells. Patient received vaginal brachytherapy. PET/CT three months later showed persistent, unchanged metabolically active left para-aortic lymphadenopathy. A repeat biopsy showed no malignancy. The scan also showed persistent chronic nephrolithiasis and obstructive uropathy of the left kidney with severe parenchymal atrophy. Uterenoscopic stone extraction with holmium laser lithotripsy and stent placement was performed. Patient remains without evidence of cancer recurrence 30 months after surgery.
Conclusions
This case shows the importance of using the pre-test probability when interpreting test results. PET/CT scan is highly sensitive and specific for endometrial cancer. However, para-aortic lymph node metastasis without pelvic lymph node metastasis from endometrial carcinoma is very rare (low pre-test probability). This low pre-test probability raised the concern about the PET/CT findings. The patient was spared the toxicity of unnecessary chemotherapy and extended field radiation. It was concluded that the findings on PET scan were related to the inflammatory process in the kidney associated with the nephrolithiasis and chronic obstructive uropathy. This case shows the importance of taking into the account the pre-test probability when interpreting any test.
#186 A different take on cardio-oncology: metastatic angiosarcoma presenting as a primary cardiac tumor
C Cutrer*
JC Henegan
The University of Mississippi Medical Center, Jackson, MS
Introduction
Cardiac tumors are very rare, mostly presenting as distant metastases. Only about 0.5% present as primary cardiac tumors and of those, the majority are benign, typically atrial myxomas (1). Angiosarcomas can rarely present as primary cardiac tumors and tend to be very aggressive. We present a case of a patient who presented with new coronary artery disease complicated by recurrent pericarditis and ultimately found to have metastatic angiosarcoma originating from the right atrium.
Case Report
Our patient is a 57 year old African-American male with a past medical history of hypertension and poly substance abuse who initially presented in January 2021 with chest pain and found to have acute coronary syndrome. He was taken for cardiac catheterization and percutaneous intervention (PCI) was performed with stent placement in left anterior descending (LAD) artery. A few weeks after his PCI, patient was readmitted for pericarditis and also complained of fatigue and weight loss, so computerized tomography of the chest, abdomen and pelvis (CT CAP) was obtained to rule out malignancy and it did not show any evidence of disease. Over the next few months, our patient had recurrent chest pain and weight continued to decline as fatigue worsened. He finally represented to the emergency room in July 2021 with chest pain and CT CAP was again obtained, only this time showing a large cardiac tumor abutting the right atrium and ventricle and evidence of metastatic disease throughout his vertebra, lungs and liver. Patient was referred to Oncology and had a biopsy of a bone lesion done via interventional radiology (IR), which showed metastatic angiosarcoma. We discussed palliative chemotherapy with single agent paclitaxel and initially patient agreed but there were delays over the next few weeks. By the time patient was able to make it back to clinic for treatment in early September, he had lost considerable weight and was wheelchair or bed bound for the majority of the day due to fatigue, weakness and pain. After further discussion, he decided to pursue hospice at home with family.
Discussion
Primary cardiac tumors are rare but when present, can be very aggressive. Angiosarcomas account for about 30% of primary malignant cardiac tumors and are typically very aggressive with a median overall survival of 4–6 months when unresectable (2). Typical treatment is surgical when feasible but chemotherapy and radiation therapy are often used, as well. Chemotherapy typically consists of taxane or anthracycline-based regimens (3). A small single arm study demonstrated a 25% (4/16) response rate for angiosarcomas to the combination of nivolumab and ipilimumab after prior chemotherapy which may lead to evaluations of this immunotherapy combination in first line therapy (4). In summary, prompt diagnosis and multidisciplinary treatment planning is important when taking care of patients with primary cardiac tumors.
#187 Pseudothrombotic microangiopathy and pancytopenia as a rare presentation of vitamin b12 deficiency
M Darweesh*
F Ghanem
R Musa
D Nunley-Gorman
East Tennessee State University James H Quillen College of Medicine, Johnson City, TN
Case Report
A 62-year-old male presented to our hospital with a few days of worsening dyspnea, associated with numbness in the left lower extremity, dizziness and transient brief chest pain that was described as a sharp intermittent pain. He denied any fever, chills, nausea, vomiting, diarrhea, headache, or recent ill contacts. The patient also denied any family history of blood or bone morrow disease. He had been released from incarceration 2 days prior to the presentation.
Complete blood count revealed pancytopenia with hemoglobin of 6.8 g/dL, MCV of 112 fL, white blood cell count of 1.2 K/uL, and platelet count of 78 K/uL. The patient was transfused with packed red blood cells and then admitted to the inpatient medicine ward for further treatment and evaluation. Blood smear confirmed the pancytopenia with severe neutropenia, macrocytosis, and moderate thrombocytopenia. In addition, it showed erythrocytes with marked poikilocytosis including occasional schistocytes and teardrop cells.
His lab investigations were notable for B12 level below 150 pg/mL (Normal range 211–911), fibrinogen of 144 mg/dL , haptoglobin less than 10 mg/dL, LDH of 1013 U/L. Other lab studies including troponin, ferritin, TIBC, serum iron, vitamin B1, PT/INR, PTT, SPEP, COVID-19, EBV, CMV, HIV, Hepatitis A, B, and C were all unrevealing. Abdominal ultrasound was significant for splenomegaly. CT head and chest x-ray were unremarkable. After starting treatment with cobalamin therapy, the patient has shown improvement in terms of cell counts, resolution of hemolysis. He also reported significant improvement in tingling and dizziness. All this confirms the diagnosis.
Vitamin B12 deficiency manifestations can vary between asymptomatic, mild, and severe. In our case, the patient presented with pseudothrombotic microangiopathy and pancytopenia. Both are rare and serious manifestations of vitamin B12 deficiency. Physicians should be aware of cobalamin deficiency as one of the etiologies for pancytopenia and pseudothrombotic microangiopathy. Therefore, an early recognition and treatment is crucial.
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