A multifaceted role of bisphosphonates from palliative care to anti-cancer therapy in solid tumors.

INTRODUCTION: Bisphosphonates (P-C-Ps) also called diphosphonates are the structural analogs of naturally occurring pyrophosphates. Bisphosphonates are traditionally used and shown to provide long-term success in the treatment and prevention of osteoporosis and other bone loss pathologies. Furthermore, bisphosphonates are gaining popularity in the present era of cancer therapeutics and prevention. The usage of bisphosphonates as adjuvant or neoadjuvant therapy, either as a single agent or combined with other chemotherapy, has been studied in different solid tumors. This review aims to present the various roles of bisphosphonates in solid tumors. DATA SOURCES: Articles in MEDLINE/PubMed and the National Institutes of Health Clinical Trials Registry (http://www. Clinicaltrials.gov) between 1 January 2011 and 1 February 2022 were extracted using MeSH terms "bisphosphonates/diphosphosphonates and mechanism," "bisphosphonates and breast cancer," "bisphosphonates and prostate cancer," "bisphosphonates and lung cancer," "bisphosphonates and cancer risk," and "bisphosphonates and adverse events." Manual searches of some major oncology journals were also conducted. DISCUSSION: This review article focuses on the antitumor activity of bisphosphonates, safety profile, and the role of bisphosphonates as preventive, neoadjuvant, and adjuvant chemotherapy. A significant improvement in overall survival and cancer-specific survival and recurrence-free survival with the usage of bisphosphonates is noted in breast cancer patients, particularly in post-menopausal women. Though great progress has been achieved in over 20 years, further research is needed to identify the subgroup of patients that are most likely to benefit from adjuvant bisphosphonate therapy and to determine regimens with greater efficacy and better safety profile.

A successful initiation of treatment of Hodgkin's lymphoma with adriamycin-bleomycin-vinblastine-dacarbazine dose reduction in a patient with fulminant hepatic failure and co-infection with human immunodeficiency virus and hepatitis B.

INTRODUCTION: Hodgkin lymphoma is a highly curable lymphoproliferative malignancy with an overall relative survival rate of 87.4%. It is characterized by multinucleated Reed-Sternberg cells which are mostly derived from B cells in the germinal center. CASE REPORT: We present a case of a 40-year-old gentleman with acquired immunodeficiency syndrome who presented with Stage 4b Hodgkin lymphoma complicated with fulminant hepatic failure and direct hyperbilirubinemia. The initial presentation of Hodgkin lymphoma as cholestatic jaundice is extremely rare. MANAGEMENT AND OUTCOME: Though the survival rate with chemotherapy is high, the fulminant hepatic failure made the situation challenging with the use of chemotherapeutic regimens that require hepatic excretion. He received dose reduced adriamycin-bleomycin-vinblastine-dacarbazine regimen [doxorubicin 12.5 mg (6.75 mg/m2), bleomycin 18 units (10 units/m2), vinblastine 3 mg (1.5 mg/m2), dacarbazine 380 mg (190 mg/m2)] as well as bictegravir/emtricitabine/tenofovir alafenamide since admission for treatment of human immunodeficiency virus and hepatitis B. He started responding with the first cycle of dose reduced adriamycin-bleomycin-vinblastine-dacarbazine regimen with bilirubin levels trended down and normalized as well as his clinical condition improved. He received the full dose of adriamycin-bleomycin-vinblastine-dacarbazine on day 15. DISCUSSION: Our case report emphasizes that the early usage of dose reduced adriamycin-bleomycin-vinblastine-dacarbazine regimen can restore hepatic function and can achieve improvement in hepatic function allowing the delivery of full-dose chemotherapy.

Skull Metastasis With Orbital Invasion as a Primary Manifestation of Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is a common worldwide cancer with a poor prognosis despite treatment advancements. Patients typically exhibit signs and symptoms pertaining to the liver. Extrahepatic metastasis of HCC is documented to be as low as 5% of cases. Bone metastasis ranks third following lungs and regional lymph nodes. The typical locations for bone metastasis include the vertebral column, pelvis, femora, and ribs, with skull metastasis, being reported in less than 1.6% of cases. Herein, we describe a case of HCC presenting with skull metastases and orbital invasion as the initial manifestation.

A Nearly Missed Case of Mitral Bioprosthetic Paravalvular Leak (PVL)-Related Waring Blender Syndrome Treated With Transcatheter Mitral PVL Closure.

A 72-year-old woman with recently diagnosed non-small cell lung cancer, who underwent cardiac bypass and bioprosthetic mitral valve replacement presented to our cancer center with lightheadedness, severe fatigue, and shortness of breath. Initial blood tests showed mild hemolytic anemia. The patient also complained of occasional bright red bleeding per rectum. Esophagogastroduodenoscopy and colonoscopy did not reveal an acute source of bleeding. An initial transesophageal echocardiogram did not show significant valvular or paravalvular abnormalities. Meanwhile, the patient's hemolytic anemia worsened. She received eight units of packed red blood cell transfusions. Schematic workup for hemolytic anemia revealed negative Coomb's test, positive urine hemosiderin, normal ADAMTS13 activity, and absent splenomegaly. A relook of the patient's transesophageal echocardiogram (TEE) showed a small paravalvular leak of the bioprosthetic mitral valve. The patient was referred to a tertiary center, and repair of the perivalvular leak with glue resolved her hemolytic anemia, subsequently improving the lab values, symptoms, and quality of life. This case highlights the schematic workup of hemolytic anemia and also the importance of recognizing the association between hemolytic anemia and valvular abnormalities.

A Rare Case of Acute Myeloid Leukemia Initially Presenting With Fever of Unknown Origin and Rapidly Progressing Pericardial Effusion.

This case report highlights a patient who had persistent fevers for weeks and rapidly progressing pericardial effusion following a positive test for coronavirus disease 2019 (COVID-19) two weeks before presentation to the hospital. The initial thought was that her fever was of infectious etiology, but relevant investigations led to the diagnosis of acute myeloid leukemia (AML). AML, which is characterized by clonal expansion of immature "blast cells" in the peripheral blood and bone marrow resulting in ineffective erythropoiesis and bone marrow failure, is the most prevalent form of leukemia. It is the most aggressive form of leukemia, which has varying prognoses determined by the subtypes. This report explores the association between AML, fever of unknown origin, and pericardial effusion, shedding light on a notable clinical aspect. Fever in AML may be attributed to underlying inflammatory processes, cytokine dysregulation, or bone marrow failure. Recognition of fever as a potential indicator of AML contributes to enhanced clinical vigilance. Pericardial effusions and cardiac tamponade, although rare, can be a presenting feature of AML, and can present side by side with fever of unknown origin as seen in this case report.

Bleeding Diathesis in Multiple Myeloma: A Rare Presentation of a Dreadful Emergency With Management Nightmare.

Multiple myeloma is a neoplastic disorder of plasma cells. An abnormal coagulation profile, though commonly seen in multiple myeloma, can rarely manifest as life-threatening hemorrhagic complications. Bleeding tendencies in multiple myeloma can be explained by a variety of mechanisms such as dysfibrinogenemia, paraprotein-induced platelet dysfunction, shortened platelet survival, damage to the vascular endothelium, and acquired von-Willebrand syndrome. Herein, we report a 61-year-old female who presented with the signs and symptoms of hemorrhagic shock with multiple myeloma, which remained refractory to a massive transfusion protocol. Her condition stabilized when she was started on dexamethasone and antifibrinolytic infusion targeting acquired dysfibrinogenemia. To the best of our knowledge, hemorrhagic shock secondary to dysfibrinogenemia is an unusual phenomenon in multiple myeloma.

Cryoglobulinemia unmasked by nivolumab in a patient with hepatitis C-induced hepatocellular carcinoma: A case report and literature review.

Hepatocellular carcinoma (HCC) is ranked the fifth-most common cancer in men and ninth most common cancer in women. Immunotherapy has been shown effective in malignancies refractory to chemotherapy and has been used as a second-line therapies in many advanced cancers, including HCC. The advent of immunotherapy has resulted in a brand-new set of side effects, and it has been proposed that it was related to over activated immune system. Herein, we presented the case of 59-year-old African American gentlemen who was diagnosed with HCC caused by Hepatitis C virus, for which he was started on chemotherapy and immunotherapy. However, the patient developed cryoglobulinemia that prompted stopping both therapies and giving rituximab and steroids. We believe that the mixed cryoglobulinemia was unmasked by immunotherapy in our patient. To our knowledge, this is one of the few first cases to describe such adverse effect from immune checkpoint inhibitors.

Varicella-Zoster Virus Reactivation in AIDS Patient After Pfizer-BioNTech COVID-19 Vaccine.

Since early 2020, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has affected millions of individuals and changed the face of medicine. As the fight against COVID continues, there is still unclear long term effects; although as time passes, more and more is being updated, in regards to the risks of exposure, length of recovery, outcomes of those infected, effectiveness of vaccines, and both expected and unique side effects of both the virus and vaccines, all in an array of individuals. This paper will review a unique topic of the SARS-CoV-2 virus and the abnormal immune response in a young patient. This case is unique due to the fact that there have been an abundance of side effects reported that are associated with the virus that affects every organ system, yet very few have affected the neurological and integumentary (skin) system. This case emphasizes the reactivation of a Herpes/Varicella-Zoster virus (VZV) in a young male shortly after he received the Pfizer-BioNTech COVID-19 vaccine. The other interesting aspect about this case is the patient's immunocompromised state, as he was diagnosed with HIV several years before this viral reactivation occurred. The interesting aspect about this was trying to understand whether the VZV was truly reactivated because of an overly stressful immune reaction in response to the Pfizer-BioNTech COVID-19 vaccine or was it mainly due to the patient's already weak immune system, or even a combination of both? The in-depth review will evaluate whether there should be more done in regards to bringing more awareness about potential side effects and preparing for a VZV reactivation and/or other dermatological complications after being vaccinated. This presentation could also simply be a very unique, isolated case, and that each individual should have no hesitations regarding the Pfizer-BioNTech COVID-19 vaccine.

Hemophagocytic Lymphohistiocytosis Secondary to Disseminated Histoplasmosis in AIDS Patient.

Hemophagocytic lymphohistiocytosis (HLH) is a rare and life-threatening syndrome that is often underdiagnosed. There are limited treatments and clinical outcomes documented in adults, more so in the immunocompromised population. Here, we described the clinical features, diagnosis, treatment, and clinical outcome of an HLH secondary to histoplasmosis in an AIDS patient.

Tocilizumab and Thromboembolism in COVID-19: A Retrospective Hospital-Based Cohort Analysis.

Background Tocilizumab, an interleukin-6 (IL-6) receptor antagonist, has been used in patients with coronavirus disease 2019 (COVID-19) as an anti-cytokine agent. IL-6 also plays a complex role in hemostasis and thrombosis. We observed a transient elevation of D-dimer in our patients who received tocilizumab, which triggered this study. Methods A retrospective hospital-based cohort analysis of patients with confirmed COVID-19 who received tocilizumab during the study period of March 15, 2020, to May 20, 2020, was conducted. We retrieved demographic, clinical, and laboratory data, and patients who were receiving therapeutic anticoagulation therapy prior to tocilizumab administration were excluded. Descriptive analysis was performed, and the cause of death and trends of D-dimer and inflammatory markers were studied. Results Out of the 436 confirmed COVID-19 patients admitted during the study period, 24 met the inclusion criteria. Their median age was 47.5 years. They were 18 males and 6 females; 15 patients survived and nine expired. Of the group that survived, 12 received therapeutic anticoagulation. Of the seven patients who did not receive therapeutic anticoagulation, four expired (one from sepsis and three probably from thromboembolic complications) compared to five deaths in the 17 patients who received therapeutic anticoagulation (four from sepsis and one possibly from thromboembolic complications). Conclusions The interplay between IL-6, IL-6 receptor antagonist, and venous thromboembolism is complex. We observed a transient elevation of D-dimer in COVID-19 patients who received tocilizumab, and a trend toward increased death secondary to thromboembolism. This observation is novel and highlights the potential thrombophilic side effects of tocilizumab.

Left ventricular thrombus complicated by acute limb ischemia in a patient with HIV.

Left ventricular thrombus typically occurs in patients with impaired left ventricular function such as aneurysm, dilated cardiomyopathy, or post-myocardial infarction. Untreated HIV infection is known to increase the risk of venous thromboembolism and cardiovascular disease. However, the pathophysiology remains uncertain; some studies have proposed chronic inflammation as the underlying etiology. Nonetheless, left ventricular thrombus is extremely rare among persons living with HIV with no known underlying cardiac disease. Herein, we report an unusual case of a 55-year-old homeless and heterosexual male with past medical history of HIV, who has mildly reduced left ventricular function and a nonmobile, medium size left ventricular thrombus. Patient was initially treated with therapeutic dose of enoxaparin, and subsequently developed acute embolic occlusion of right femoral artery that lead to an above knee amputation. To our knowledge, left ventricular thromboembolism complicated with acute embolic ischemia in persons living with HIV is extremely rare. The presenting case will definitely add to the current body of knowledge and will raise awareness among physicians, in recognizing the rare association between HIV and arterial thromboembolism.

Hyperprogressive Disease in an Advanced Stage Colon Cancer Patient on Pembrolizumab: A Case Report.

The emergence of immune checkpoint inhibitors (ICIs) in recent years has transformed the landscape of the management of solid tumors. The advancement of immunotherapy has resulted in a brand new set of adverse outcomes not previously seen in classical chemotherapy. One such adverse effect has been termed as hyperprogressive disease (HPD), a phenomenon characterized by rapid tumor progression, which often leads to devastating outcomes. In this report, we present a unique case of a 48-year-old African American female who initially presented with abdominal pain, fatigue, and weight loss. Subsequent CT scan showed extensive irregular wall and luminal narrowing with an eccentric mass and adenopathy along the portacaval space. Tumor markers were found to be elevated and genetic testing was done. The patient was diagnosed with stage IIIC colon cancer with K-RAS wild type, associated with Lynch syndrome. The patient underwent surgical resection, chemotherapy, and targeted therapy for progressive/stage IV disease. In light of the progression of the disease, pembrolizumab was introduced into the treatment regimen. One month after the treatment, a repeat CT scan showed enlargement of the metastatic lesion with almost double the size. The progression of the disease was so rapid and, ultimately, pembrolizumab administration was withheld and the patient passed away after about two months on pembrolizumab. To our knowledge, this is one of the few cases of HPD reported in patients with advanced colon cancer, particularly in one with Lynch syndrome. Further studies are warranted to understand why some individuals benefit from immunotherapy, whereas others experience grave outcomes.

COVID-19 Associated Coagulopathy in the Setting of Underlying Malignancy.

Coronavirus disease 2019 (COVID-19) associated coagulopathy is a well-recognized predictor for morbidity and mortality in COVID-19 patients. Both deep vein thrombosis (DVT) and pulmonary embolism (PE) have been reported in COVID-19 patients. Nonetheless, there are no consensus guidelines on the use of therapeutic coagulation in this group of patients. We herein present a unique case of a confirmed COVID-19 patient with metastatic ovarian cancer who presented with DVT and PE despite being on therapeutic anticoagulation, highlighting the unpredictability of COVID-19 associated coagulopathy. This case study raises the awareness that the thrombophilic state in metastatic malignancies is potentially augmented by COVID-19. We also discuss the complexity of making anticoagulation treatment decision in COVID-19 patients in the absence of evidence-based guidelines.

A Rare Case of Evans Syndrome in a Patient With Ulcerative Colitis.

Evans syndrome (ES) is an autoimmune condition that presents with two or more cytopenias, which includes simultaneous or sequential development of warm autoimmune hemolytic anemia (AIHA) and immune thrombocytopenic purpura (ITP). The association of ES with ulcerative colitis (UC) was only reported once in the literature. Herein, we present a case of a 66-year-old male patient with a history of UC, who was diagnosed with ES secondary to UC, for which he was treated with steroids. Recognizing this rare association is important as prompt treatment with intravenous immunoglobulin and steroids will improve the prognosis and reduce the risk of complications.

A rare and unusual presentation of Epstein-Barr virus-associated diffuse large B-cell lymphoma involving colon as the primary site.

Lymphoproliferative malignancies can involve both nodal- and extra-nodal tissues. The most common extranodal site involved is the gastrointestinal (GI) tract, and it is secondary to the widespread primary nodal disease. However, about 33% of non-Hodgkin's lymphoma primarily arise from tissues other than lymph nodes, spleen, or bone marrow, for example, GI tract, skin, or the central nervous system and are called primary extranodal lymphomas. The most common site of GI localization is stomach (50%-60%) followed by small bowel. Primary colonic lymphoma is seen only in 6% of GI lymphomas and up to 0.5%-1% of all colon malignancies. Hence, primary GI lymphoma is extremely rare, and primary colonic lymphoma is an even rarer occurrence. There is clearly a paucity of cases reported in literature resulting in unclear treatment protocol. Here, we report a case of a 51-year-old man who presented with abdominal pain, weight loss, and bright red blood per rectum. A colonoscopy revealed diffuse bleeding ulcers involving the entire colon. Pathology was consistent with primary diffuse large B-cell lymphoma arising from the colon. The patient was started on treatment with rituximab, cyclophosphamide, adriamycin, vincristine, and prednisone.

Mycobacterium chelonae infection of the parotid gland.

Mycobacterium chelonae can cause numerous infections, including lung disease, local cutaneous disease, osteomyelitis, joint infections and ocular disease. With the exception of lung disease, these syndromes commonly develop after direct inoculation. The most common clinical presentation in immunocompetent individuals is skin and soft tissue infection. We present a case of M. chelonae infection of the parotid gland that was successfully treated with clarithromycin monotherapy. To our knowledge, this is the first case report of M. chelonae parotitis in an adult.

Characteristics of colorectal cancer in the human immunodeficiency virus-infected African American population.

Colorectal Cancer (CRC) is the second leading cause of cancer mortality in the United States. African Americans (AAs) have the highest incidence of CRC of any American ethnic group. Survival from CRC in AAs is lower than in Caucasians, and the mean age of CRC development in AAs is younger. The AA community also has a high rate of HIV infection, accounting for 50.3% of all cases despite making up only 13.6% of the population. This retrospective cohort study identified 17 AA HIV patients with CRC. The patients were matched with 42 HIV-negative CRC patients (controls), based on age, sex, and TNM stage. Data were obtained from 3 hospitals in New Jersey: St. Michael's Medical Center, Trinitas Medical Center and St. Joseph's Medical Center. The age, sex, HIV status, tumor site, stage, drug usage, Hepatitis C status, and survival outcome of subjects and controls were compared. Data from the Surveillance Epidemiology & End Results (SEER) specific to AAs were also compared. The mean age of CRC diagnosis was younger, 50.7 years (median: 52 years, range: 35-71 years), versus 59.42 years (median: 66 years) (P < 0.0001) in the SEER AA population. Of the patients, 29.4% were diagnosed with CRC at less than 45 years of age, versus only 6.35% of the SEER AA population (P < 0.0002). The male-to-female ratio was 11:6. Seven individuals used IV drugs, and 7 had hepatitis C. The mean CD4+ T-cell count was 510.81 cells/mm(3) (median 419). At the time of CRC diagnosis, the average duration of HIV infection was 7.6 years (range 0-22.4 years).Of patients, 87.5% had left-sided CRC, versus 57.55% of the SEER population (P < 0.024). Of the patients, 52.94% had stage III-IV, at diagnosis, versus 43.84% in SEER. There was no statistically significant survival difference between the cases and controls. In our cohort of HIV-infected AA's with CRC, the staging and outcome of CRC did not appear to be affected by the degree of immunosuppression. HIV-infected AA with CRC presented with a higher percentage of left-sided CRC than AA's without HIV. Additionally, AAs with HIV tended to be younger at the time of CRC diagnosis. Our findings suggest that screening for CRC should be offered to HIV-infected AAs before the age of 45, and that sigmoidoscopy with fecal occult blood testing might be an acceptable screening modality. However, the exact age of initiation, optimal frequency, and preferred method of screening (colonoscopy vs. sigmoidoscopy) in this population requires further study.