Racial and socioeconomic disparities in survival among patients with metastatic Non-Small cell lung cancer.

BACKGROUND: Immune checkpoint inhibitors (ICI) have profoundly impacted survival among patients with metastatic non-small cell lung cancer (NSCLC). However, population-based studies evaluating this impact on survival by race and socioeconomic factors are lacking. METHODS: We utilized the SEER-Medicare database to identify patients with metastatic NSCLC diagnosed between 2015 and 2019. The primary study outcomes were the receipt of an ICI and overall survival (OS). Chi-square tests and logistic regression were utilized to identify demographic factors associated with receipt of ICI. The Kaplan-Meier method was used to calculate 2-year OS rates, and log-rank tests were used to compared survival by race/ethnicity. RESULTS: Out of 17,134 patients, approximately 39% received an ICI. Those diagnosed with cancer recently (in 2019), who are relatively younger (<85 years old), non-Hispanic white, non-Hispanic Asian, or Hispanic, living in high socioeconomic status or metropolitan areas, not Medicaid eligible, and with adenocarcinoma histology were more likely to receive ICI. The 2-year OS rate from diagnosis was 21% for the overall population. The 2-year OS rate from ICI initiation was 30%, among those who received at least one cycle and 11% among those who did not receive ICI. The 2-year OS rates were higher among non-Hispanic whites (22%) and non-Hispanic Asians (23%) compared to non-Hispanic Blacks (15%) and Hispanics (17%). There was no significant racial differences in survival for those who received ICI. CONCLUSION: ICI utilization rates and the resulting outcomes were inferior for certain vulnerable groups, mandating the need for strategies to improve access to care.

A Simple Vitamin Deficiency With Life-Threatening Complications: A Case of B12 Deficiency and Hyperhomocysteinemia-Induced Thrombosis.

While macrocytic anemia is common in vitamin B12 deficiency, rarely, pancytopenia and hemolytic anemia can occur. Homocysteine levels are elevated in severe B12 deficiency, and this is linked to thrombus formation with potentially life-threatening complications. We present a patient with severe vitamin B12 deficiency complicated by hyperhomocysteinemia and obstructive shock from pulmonary embolism. A 56-year-old male with no medical history presented to the hospital with altered mentation. The patient's family stated he was experiencing bilateral paresthesias of his lower extremities, progressive depression, anxiety, and insomnia. Initial vitals were blood pressure of 76/36, heart rate of 70 beats per minute, respiratory rate of 14, and temperature of 36.3 degrees Celsius. He was intubated due to severe encephalopathy. Relevant labs indicated severe macrocytic anemia, thrombocytopenia, decreased B12 levels, elevated methylmalonic acid, and elevated homocysteine. Imaging demonstrated a right common femoral vein thrombosis and subsegmental pulmonary emboli. Peripheral blood smear revealed schistocytes, anisopoikilocytosis, and decreased platelet count. The patient required fluid resuscitation, antibiotics, and multiple blood products. Vitamin B12 was administered intramuscularly, which improved the anemia. Esophagogastroduodenoscopy (EGD) demonstrated gastritis. Gastric and duodenal biopsies were negative for Helicobacter pylori and celiac disease. He was negative for intrinsic factor (IF) antibodies but had elevated gastrin levels. An intravenous unfractionated heparin infusion was started when the platelet count was above 50000. The patient was extubated after seven days. Heparin was transitioned to apixaban and an inferior vena cava (IVC) filter was placed. Hyperhomocysteinemia is a known pro-thrombotic factor that can lead to the development of venous thromboembolism. B12 malabsorption can stem from inflammatory bowel disease, celiac disease, gastritis, pancreatic insufficiency, gastrectomy, gastric bypass surgery, or antibodies to IF. While this case showed gastritis and negative IF antibodies, gastrin levels were elevated, indicating a mixed picture. This highlights the challenge of definitively diagnosing pernicious anemia as the cause of vitamin B12 deficiency. Vitamin B12 deficiency may lead to critical illness in which thromboembolism develops secondary to hyperhomocysteinemia.

Primary Combined Hepatocellular-Cholangiocarcinoma: A Case of Underdiagnosed Primary Liver Cancer.

Combined hepatocellular-cholangiocarcinoma (CHC) is a rare primary tumor of the liver. Histologically, it comprises components of both hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC) but is associated with a worse prognosis. International guidelines regarding its management are scarce, with surgical management (major hepatectomy) being the treatment of choice. In this report, we present a challenging case of a 73-year-old male with primary CHC who was not a surgical candidate but underwent hepatic artery radioembolization instead.

Lumpectomy followed by radiation improves survival in HER2 positive and triple-negative breast cancer with high tumor-infiltrating lymphocytes compared to mastectomy alone.

OBJECTIVE: The goal was to compare the 5-year DFS and 5-year OS in patients with early-stage human epidermal growth factor receptor 2 breast cancer (HER2+ BC) and triple-negative breast cancer (TNBC) in relation to the amount of stromal tumor-infiltrating lymphocytes (TILs) after locoregional management by either mastectomy without radiation or lumpectomy and whole-breast radiotherapy (RT). METHODS: This was a retrospective review of HER2+ BC and TNBC patients' charts and histopathology slides with clinical stage of T1-T2 N0 who presented at our facility between January 2009 and December 2019. Locoregional treatment included either mastectomy without RT (M) or lumpectomy with RT (L+R). TILs were assessed by three pathologists using the guidelines of the 2014 TILs working group. A competing risk model and Kaplan-Meier analysis were used to analyze correlations between TILs levels and clinical outcome. RESULTS: We reviewed 211 patients' charts. Of them, 190 proceeded to the final analysis. Patients were split into groups of "low TILs" and "high TILs" based on a 50% TILs cut-off. Of them 26% had high TILs, 48% received RT, 97% received chemotherapy, all HER2+ BC patients received HER2-directed therapy and all HER2+ BC that were also hormone receptor positive (HR+) received endocrine therapy (ET). In patient with low TILs, L+R did not improve outcomes compared to M. Moreover, patients with high TILs had a significant improvement of their DFS and OS with L+R when compared to M. CONCLUSION: The results of our study reflect that a selected group of HER2+ BC and TNBC with elevated TILs, L+R is associated with improvement of 5-year DFS and 5-year OS.

Outcomes of in-hospital cardiopulmonary resuscitation for cardiac arrest in adult patients with metastatic solid cancers: A Nationwide Inpatient Sample database analysis from 2012 to 2014.

BACKGROUND: Cardiopulmonary arrest is known to have a poor prognosis, further worsened by preexisting comorbidities. With improved treatment, the prevalence of metastatic cancers is rapidly increasing; however, the outcomes of in-hospital cardiopulmonary resuscitation (ICPR) remain to be well described. This study examines the epidemiology, associations, and outcomes of ICPR in these patients. METHODS: This is a retrospective cohort analysis of the Nationwide Inpatient Sample database (2012-2014) including patients aged ≥18 years with metastatic cancers. Primary outcome was inpatient mortality following ICPR. Factors associated with the primary outcome were analyzed using univariate/multivariate logistic regression analysis. RESULTS: Among all admissions with metastatic cancers (n = 5,500,684), 0.47% (n = 26,070) received ICPR. Inpatient mortality was 81.77% (n = 8905) versus 68.90% among those without metastatic solid cancers and receiving ICPR. Inpatient palliative care encounter was documented in 18.95% of patients with metastatic cancer who received ICPR. On multivariate logistic regression, some of the notable factors associated with higher mortality included being of African American or Hispanic race and hospital admission over the weekend. Factors associated with lower mortality included female sex, elective admission, and head and neck as the primary site. Admissions with ICPR were associated with higher mean total charge of hospitalization (by $48,670) compared with admissions without ICPR. Of those who survived ICPR, 43.82% were transferred to another facility after discharge. CONCLUSIONS: Among adult patients with metastatic solid cancers having ICPR, 81.8% died within the same hospital admission. Race and admission type predicted mortality. Despite known poor prognosis, only a minority had palliative care. LAY SUMMARY: Cardiopulmonary resuscitation during hospitalization for patients who have metastatic cancer has a very poor outcome with a mortality rate of 81.77%. Inpatient cardiopulmonary resuscitation in these patients is also associated with a significantly higher cost of care, longer length of stay, and high rate of transfer to a different health care facility upon discharge. Knowledge of these outcomes is helpful in discussing the pros and cons of pursuing aggressive resuscitative interventions with patients and families.

Coagulation and anticoagulation in COVID-19.

COVID-19 has become a pandemic in the United States and worldwide. COVID-19-induced coagulopathy (CIC) is commonly encountered at presentation manifested by considerable elevation of D-dimer and fibrin split products but with modest or no change in activated partial thromboplastin time and prothrombin time. CIC is a complex process that is distinctly different from conventional sepsis-induced coagulopathy. The cytokine storm induced by COVID-19 infection appears to be more severe in COVID-19, resulting in development of extensive micro- and macrovascular thrombosis and organ failure. Unlike conventional sepsis, anticoagulation plays a key role in the treatment of COVID-19, however without practice guidelines tailored to these patients. We propose a scoring system for COVID-19-coagulopathy (CIC Scoring) and stratification of patients for the purpose of anticoagulation therapy based on risk categories. The proposed scoring system and therapeutic guidelines are likely to undergo revisions in the future as new data become available in this evolving field.

Primary Leiomyosarcoma of the Mesentery: A Case Report With Review of Literature.

Mesenteric leiomyosarcoma (LMS) is a rare gastrointestinal mesenchymal tumor. It was often misdiagnosed as a gastrointestinal stromal tumor (GIST) until the introduction of immunohistochemistry staining (IHC) in 1998. Currently, a positive IHC staining for smooth muscle markers represents the main diagnostic modality. Herein, we present a case of Mesenteric LMS in a 68-year-old woman, who presented with nausea, vomiting, and abdominal pain and was found to have a right-sided mesenteric tumor encasing the right ureter, with right hydroureteronephrosis. The patient underwent surgical removal of the tumor and IHC stains were compatible with LMS. She achieved remission until she developed recurrence 12 months after initial diagnosis and subsequently expired due to postoperative complications when re-resection was attempted. Typically, mesenteric LMS carries a poor prognosis with a propensity for hematogenous metastasis. In the absence of a standardized protocol for therapy, early surgical resection is the only known curative modality but with a high risk of recurrence.

Concomitant acute interstitial nephritis and autoimmune hemolytic anemia induced by omeprazole.

Proton pump inhibitors (PPI)-induced acute interstitial nephritis and autoimmune hemolytic anemia can occur concomitantly, which should prompt discontinuation of PPI. PPI should wisely be prescribed and discontinued when no longer needed.

Prognostic Utility of Tumor-Infiltrating Lymphocytes in Noncolorectal Gastrointestinal Malignancies.

BACKGROUND: Tumor-infiltrating lymphocytes (TILs) and mismatch repair gene mutation (MMR) status are emerging biomarkers in immunotherapy. MMR status and TILs have significant clinical implications with regard to treatment with checkpoint inhibitors. We designed a study to determine the frequency and prognostic utility of TILs and MMR in advanced unresectable noncolorectal gastrointestinal (NCGI) malignancies. METHODS: This is a retrospective cohort study of patients who were diagnosed with advanced noncolorectal gastrointestinal tumors. Biopsy specimens were tested for MMR status by immunohistochemistry along with evaluation of TILs. Kaplan-Meier analysis was performed to determine the impact of TILS and MMR on survival. RESULTS: We analyzed 146 patients; the mean age at diagnosis was 66.4 ± 11.2 years. 65.8% patients were male, and 62.3% patients had stage 4 disease. All cases had proficient MMR status. The percentage of patients with TILs >5 was 50.7%. There was no statistically significant difference in median overall survival (OS) by TILs when stratified by stage of tumor. When stratified by type of tumor, median OS by TILs level was significantly different for hepatocellular cancers (⩽5 TILs, 86 days versus >5 TILs 312 days, P = .031). CONCLUSIONS: Our study suggests that MMR-deficient tumors are quite rare in advanced NCGI malignancies. More than 5 TILs per high power field, evaluated simply on a routine hematoxylin and eosin-stained glass slide confer a better prognosis to most noncolorectal gastrointestinal malignancies, especially hepatocellular carcinoma. This has immense clinical utility with regard to eligibility for immunotherapy.

Benign Multicystic Peritoneal Mesothelioma: A Rare Condition in an Uncommon Gender.

Benign Multicystic Peritoneal Mesothelioma (BMPM) is a rare condition that arises from the abdominal peritoneum. Fewer than 200 cases have been reported worldwide. BMPM usually affects premenopausal women and is extremely rare in men. Many factors are suspected to contribute to its development, such as previous surgery, endometriosis, and familial Mediterranean fever. The main management is surgical resection; however, it is estimated that the recurrence rate is up to 50%. Malignant transformation is rare. We report a case series of three male patients who were diagnosed with BMPM and were treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC).

Composite Lymphoma: Opposite Ends of Spectrum Meet.

An 18-year-old African-American female presented with an episode of syncope. Initial investigations revealed large lung mass with invasion into right atrium along with lesions in kidneys and liver. Patient also developed superior vena cava syndrome due to lung mass. Biopsy of lung mass revealed diagnosis of composite lymphoma with involvement by primary mediastinal B-cell lymphoma (PMBCL) and classical Hodgkin lymphoma. Patient was started on dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin and rituximab (EPOCH-R) with complete response to treatment. This case represents an extremely rare type of aggressive lymphoma and can guide clinicians in managing such cases since there are no standard guidelines for treatment. To the best of our knowledge, this is the first reported case of composite lymphoma of PMBCL and classical Hodgkin lymphoma successfully treated with dose-adjusted EPOCH-R regimen.

Nivolumab induced myxedema crisis.

BACKGROUND: Nivolumab is an anti-programmed cell death (anti-PD-1) monoclonal antibody that is approved by Food and Drug Administration for treatment of metastatic non-small cell lung cancer, metastatic melanoma, relapsed Hodgkin lymphoma and advanced renal cell cancer. We report a rare case of myxedema crisis induced by nivolumab in a patient with metastatic squamous cell carcinoma of lung. CASE PRESENTATION: Fifty three-year old woman with metastatic squamous cell carcinoma currently on treatment with nivolumab presented with diffuse facial and tongue swelling, slurred speech, depressed mentation, fatigue and weakness. Initial evaluation revealed severe hypothyroidism with thyroid stimulating hormone of 237 micro Unit/mL (Normal Reference range: 0.27-4.20 micro unit/mL) and undetectable free T4. Patient was diagnosed with nivolumab induced myxedema crisis. She was treated successfully with levothyroxine with complete resolution of her symptoms. Nivolumab was safely restarted once the symptoms of myxedema resolved. CONCLUSION: Nivolumab can cause immune-mediated endocrinopathies including thyroiditis, hypophysitis, adrenal insufficiency and type 1 diabetes mellitus. High index of suspicion and periodic measurement of thyroid function tests are recommended in patients receiving nivolumab therapy. Our case also suggests that once the myxedema crisis is treated and symptoms are resolved, nivolumab can be safely re-challenged.

Immunotherapy-associated autoimmune hemolytic anemia.

BACKGROUND: Immunotherapy has been widely used in the treatment of several solid and hematologic malignancies. Checkpoint inhibitors have been the forefront of cancer immunotherapy in recent years. Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death 1 (PD-1) pathway are the prototypic checkpoint targets for immunotherapy. When combined, CTLA-4 and PD-1 checkpoint inhibitors work synergistically, but with increased probability of toxicity. The following case represents an unusual adverse effect of combined treatment with ipilimumab and nivolumab used for treatment of metastatic melanoma. CASE PRESENTATION: A 43-year-old woman with metastatic melanoma presented with severe generalized weakness and fatigue. She has received two cycles of ipilimumab and nivolumab, last administered 3 weeks prior to her presentation. Initial investigations revealed severe anemia with appropriate reticulocytosis, severely elevated lactate dehydrogenase, undetectable haptoglobin level and positive direct coombs test. Patient was diagnosed with severe autoimmune hemolytic anemia secondary to ipilimumab and nivolumab. She was successfully treated with high dose steroids and rituximab. CONCLUSIONS: In our case, we present a rare but serious adverse effect of immunotherapy. We illustrate the clinical presentation and management of immunotherapy associated autoimmune hemolytic anemia. Immunotherapy has revolutionized the treatment of many malignant conditions; therefore, it is imperative for health care professionals caring for cancer patient to be familiar with the adverse effects of immunotherapy, which allow for early recognition and management of these potentially lethal side effects.

Thrombotic thrombocytopenic purpura presenting as acute coronary syndrome.

In patients presenting with thrombotic thrombocytopenia purpura and non-ST elevation myocardial infarction, prompt initiation of plasma exchange takes precedence over other invasive diagnostic procedures for coronary artery disease. Such procedures should be delayed until clinical condition and laboratory parameters have been stabilized.

Safety and efficacy of radioimmunotherapy (RIT) in treatment of non-Hodgkin's lymphoma in the community setting.

INTRODUCTION: Radioimmunotherapy (RIT) is a unique therapeutic modality that combines biologic and radiolytic mechanisms to induce tumor kill. RIT is underutilized in the community outpatient setting. METHODS: This is an institutional review of patients treated with RIT at St. John Hospital and Medical Center (SJH&MC) 2003-2011. RIT agents were dosed according to recommended guidelines. Response was assessed using the Revised Response Criteria for Malignant Lymphoma and toxicity was assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events. The primary aim was to assess overall response rate (ORR) and overall survival (OS). The secondary aim was to assess the impact of variable host and disease factors on the ORR to RIT and OS. RESULTS: Forty-eight patients were treated with RIT within the specified period at SJH&MC; of which 52% with follicular lymphoma (FL) and 46% with diffuse large B cell lymphoma (DLBCL). The majority of patients had relapsed or refractory disease (98%). Median duration of follow-up was 17 months. The ORR was 73% with 44% complete remission (CR) rate and OS of 48 months. The ORR was 79% with 58% CR rate and OS of 82 months among FL patients. Among DLBCL patients, the ORR was 65% with 30% CR rate and OS of 39 months. Response to last therapy before RIT was the only significant predictor of response to RIT and a significant predictor of OS in multivariate analyses. Prior exposure to EBRT did not predict response or survival in multivariate analyses. Toxicity was manageable and predominantly hematologic. CONCLUSIONS: RIT is effective and feasible for use in the community outpatient setting. ADVANCES IN KNOWLEDGE AND IMPLICATIONS FOR PATIENT CARE: Patients with B-cell NHL can safely receive RIT close to home. With some coordination of effort, it is not difficult for community-based cancer centers to implement this treatment modality.

Primary Cardiac Lymphoma: Lessons Learned from a Long Survivor.

Primary cardiac lymphoma (PCL) is a rare neoplasm that involves the heart, pericardium, or both. Patients with PCL have median survival of approximately 7 months. We report a 63-year-old woman with PCL treated with chemoimmunotherapy but relapsed 7 years later. She received automated implantable cardioverter-defibrillator (AICD) prophylactically shortly after the diagnosis. She presented with a breast recidive 7 years after initial diagnosis and died of relapsed small cell lung cancer. As many patients with PCL die early in the disease course due to life-threatening arrhythmias, preemptive implantation of AICD may improve mortality and prevent early death. Chemoimmunotherapy is effective in inducing remission in patients with PCL. Late and unusual pattern of relapse may be more frequent in patients with PCL and should be explored further. This case presents one of the longest surviving patients with PCL reported in the literature.