Severe Hyponatremia During First Cycle of Cyclophosphamide/Doxorubicin Chemotherapy.

Syndrome of inappropriate anti-diuretic hormone release (SIDAH) is a condition characterized by an unregulated release of anti-diuretic hormone (ADH) resulting in increased water retention and decreased plasma osmolarity. Without regulation, ADH release will cause a significant decrease in plasma sodium concentration and can present with cramping, nausea, vomiting, and in severe cases, seizures, and potentially falling into a comatose state. The causes of SIADH are variable and range from infections, some malignancies to some medications. We report a rare case of SIADH resulting from a single cycle of doxorubicin and cyclophosphamide chemotherapy in a 66-year-old female with left and right, estrogen receptor positive breast cancer who experienced seizures resulting from a dramatic drop in sodium levels.

Outcomes and management of immune thrombocytopenia secondary to COVID-19: Cleveland clinic experience.

BACKGROUND: Immune thrombocytopenia (ITP) is an acquired disease characterized by thrombocytopenia secondary to autoantibodies against platelets. Here, we report the clinical characteristics of coronavirus disease 2019 (COVID-19)-induced ITP cases. STUDY DESIGN AND METHODS: We retrospectively reviewed 3255 COVID-19 patients. COVID-19-induced ITP was diagnosed after excluding possible common causes. Bleeding severity was assessed based on the modified World Health Organization (WHO) bleeding severity score. RESULTS: We identified 11 (0.34%) patients with COVID-19-induced ITP. Of all patients, 63.6% were males and the median age was 63 years. The median time from COVID-19 diagnosis to the onset of ITP was 10 days. Bleeding observed in 63.6% of the patients. Clinically significant bleeding (WHO Grade 3) occurred in single patient who required blood transfusion. Standard treatment with glucocorticoids and intravenous immunoglobulin (IVIG) was effective in achieving excellent response in most cases. Of all patients, complete response and response to treatment were achieved in 45.5% and 27.3% patients, respectively. The median time to ITP recovery was 4 days. Eltrombopag was used in three patients who relapsed. Four patients required mechanical ventilation, and none of them survived secondary to hypoxic respiratory failure. CONCLUSION: ITP secondary to COVID-19 usually presents after the first week of symptoms beginning. Most of our patients had WHO Grade 1-2 bleeding scores. Standard treatment with glucocorticoids and IVIG is effective in achieving an excellent response. The safety of eltrombopag is not very well established in COVID-19 patients, and additional studies are needed for a better safety profile.

Prognostic impact and risk factors of cancer-associated thrombosis events in stage-IV cancer patients treated with immune checkpoint inhibitors.

BACKGROUND: Cancer-associated thrombosis (CAT) is a major cause of mortality in cancer patients. Immune checkpoint inhibitors (ICIs) have been associated with multiple side effects including CAT. The aim of this study is to investigate risk factors and prognostic impact associated with CAT events during ICIs treatment. METHODS: This is a multi-center retrospective study that included stage IV cancer patients treated with ICIs. RESULTS: We identified 552 cancer patients treated with ICIs. During follow-up time, 58 (10.5%) patients developed 67 venous thromboembolism (VTE) events while on ICIs. Anticoagulation use at the time of ICIs treatment start was associated with significantly higher VTE incidence rate (IRR: 2.23). No significant difference in VTE IRR was observed depending on response to ICIs treatment, aspirin use, or Khorana VTE risk score. Melanoma as primary cancer, Khorana score, ECOG status, and anemia at baseline were able to predict mortality. CONCLUSIONS: The incidence of CAT in stage-IV cancer patients treated with ICIs was higher in our study compared to previous reports. Control group of patients who did not receive ICIs is needed for better identification of CAT risk factors. Khorana score was a good predictor of mortality but not CAT risk and needs to be further validated in a homogenous group of patients.

New anticoagulants in cancer patient treatments.

Venous thromboembolism (VTE) is a common complication of cancer patients. Initiation of anticoagulant treatment is of vital importance once a diagnosis of VTE has been established. Unfractionated heparin and low-molecular-weight heparins (LMWH) have been the mainstay for in-hospital-based prophylaxis, both postsurgically and on medicine floors, and for the acute management of VTE. The current international guidelines, including American Society of Clinical Oncology, the American College of Chest Physicians, the European Society of Medical Oncology, and the International Society of Thrombosis and Hemostasis, recommend the use of LMWH monotherapy for the long-term management of cancer patients with established acute symptomatic VTE. Although LMWHs have become the preferred treatment for patients with cancer, problems with its use have prompted clinicians to seek newer antithrombotic agents.

Practical recommendations on incorporating new oral anticoagulants into routine practice.

The use of new oral anticoagulants (NOACs) is expected to rise significantly in upcoming years. Therefore, it is important to understand the potential uses, side effects, and management of these agents in routine practice. NOACs have major pharmacologic advantages over warfarin, including a rapid onset and offset of action, fewer drug interactions, and predictable pharmacokinetics. These agents are gaining popularity among both physicians and patients because of their ease of administration and the advantage of eliminating the requirement for regular coagulation monitoring. NOACs work to prevent and treat thrombosis by targeting either thrombin (as with dabigatran) or factor Xa (as with rivaroxaban and apixaban). In this review, we discuss practical recommendations for the use of NOACs and the risks and benefits of incorporating them into routine practice.

A Case of Secondary Hemophagocytic Lymphohistiocytosis in a Patient With T-cell Lymphoma.

Hemophagocytic lymphohistiocytosis (HLH) is a rare and life-threatening condition that results from excessive immune activation and inflammation. This condition may be triggered by various factors, including infections, malignancies, or autoimmune diseases. Here, we report the case of a 39-year-old male who developed HLH secondary to T-cell lymphoma and had a history of multiple autoimmune disorders. Our patient presented with shortness of breath and weakness which led to an admission for methicillin-resistant Staphylococcus aureus bacteremia. His hospital course deteriorated rapidly due to his worsening condition. He was confirmed to have HLH based on the HLH-2004 criteria with the presence of fever, splenomegaly, hypertriglyceridemia, hypofibrinogenemia, low natural killer cell function, high ferritin, and soluble interleukin 2 receptor levels. Peripheral blood smear and bone marrow biopsy showed atypical lymphocytes consistent with a T-cell lymphoma, but no hemophagocytosis. He was treated with dexamethasone and etoposide. Despite treatment, the patient passed away. This case aims to contribute further to the understanding of secondary HLH in the setting of T-cell lymphoma. It also illuminates how vital early recognition and treatment are in patients with secondary HLH.

Intramucosal Extent as a Marker for Advanced Disease and Survival in Gallbladder Adenocarcinoma.

BACKGROUND: Gallbladder cancer (GBC) is the most common biliary tract malignancy and has a poor prognosis. The clinical significance of focal vs diffuse GBC remains unclear. METHODS: A retrospective review was conducted on all patients with non-metastatic GBC at a quaternary care center. Pathology was reviewed, and gallbladder cancer pattern was defined based on the extent of mucosal involvement; "diffuse" if the tumor was multicentric or "focal" if the tumor was only in a single location. Patients undergoing liver resection and portal lymphadenectomy were considered to have definitive surgery. The primary outcome was overall survival and assessed by Kaplan-Meier curves. RESULTS: 63 patients met study criteria with 32 (50.7%) having diffuse cancer. No difference was observed in utilization of definitive surgery between the groups (14 [43.8%] with focal and 12 [38.7%] with diffuse, P = .88). Lymphovascular invasion (P = .04) and higher nodal stage (P = .04) were more common with diffuse GBC. Median overall survival was significantly improved in those with focal cancer (5.1 vs 1.2 years, P = .02). Although not statistically significant, this difference in overall survival persisted in patients who underwent definitive surgery (4.3 vs 2.4 years, P = .70). DISCUSSION: Patients with diffuse involvement of the gallbladder mucosa likely represent a subset with aggressive biology and worse overall survival compared to focal disease. These findings may aid surgeons in subsequent surgical and medical decision-making for patients with GBC.

Targeted therapy for lung cancer.

Lung cancer is considered the number one killer among all cancers. Recent observations have altered the treatment paradigm for non-small-cell lung cancer (NSCLC). The discovery of activating mutations in the epidermal growth factor receptor and anaplastic lymphoma kinase positivity has made personalized treatment for NSCLC more feasible. Both erlotinib and crizotinib have been shown to be effective and safe for subgroup populations, and now personalized treatment for nonsquamous NSCLC has progressed even further. New tyrosine kinase inhibitors are being tested, resistant mutations are being studied, and new detection systems are being incorporated; all these developments will make the detection and treatment of the deadliest cancer more affordable, practical, and effective. The National Comprehensive Cancer Network has already incorporated these new developments into their guidelines for advanced nonsquamous NSCLC.

Overview of histologic variants of urothelial carcinoma: current trends and narrative review on treatment outcomes.

Background and Objective: The histologic variants of urothelial carcinoma (UC) are tumors arising from within the urothelium in which some component of the tumor morphology is other than urothelial. They are underdiagnosed, aggressive and have varying pathologic response rates to systemic chemotherapy. There are no consensus guidelines on the use of systemic chemotherapy in variant histology (VH) of UC. We performed a contemporary review on pathologic response rates to neoadjuvant systemic therapy and survival outcomes following radical cystectomy in order to provide a rationale for clinical practice recommendations on the management of UC with VH. Methods: A PubMed literature search was conducted for all English articles from inception reporting either pathological response rates to neoadjuvant treatment or survival outcomes after radical cystectomy in non-metastatic VH of UC. Key Content and Findings: Neoadjuvant chemotherapy (NAC) prior to radical cystectomy was shown to be a beneficial treatment strategy in UC with VH. The micropapillary, plasmacytoid, nested and sarcomatoid histologic variants were associated with worse survival outcomes compared to conventional UC and UC with squamous or glandular differentiation despite initial downstaging with chemotherapy. There is evidence of improved survival in patients with sarcomatoid differentiation receiving NAC compared to RC alone. The major prognostic factors that affect survival outcomes in VH of UC include histologic variant subtype, patient age, presence of lymphovascular invasion, hydronephrosis, nodal metastasis and advanced T stage at diagnosis. Recent studies demonstrate that VH of UC are heterogenous tumors and responsiveness to NAC may be a function of the molecular subtypes present. Conclusions: Based on these findings, NAC to achieve pathologic downstaging prior to radical cystectomy is recommended for MIBC with VH. Biomarkers identified by molecular profiling with immunohistochemistry will need to be validated as predictors of response to NAC in future trials.

Metaplastic Breast Cancer: Characteristics and Survival Outcomes.

Objectives Metaplastic breast cancer (MBC) is a rare neoplasm accounting for <1% of all breast cancer. We evaluated the clinical characteristics and survival outcomes of MBC. Methods Patients diagnosed with pathologically proven MBC were reviewed from the institutional breast cancer database from 2000 to 2017. Results A total of 136 patients diagnosed with MBC were included in the study. The median age of the diagnosis was 60 years, and 60% of patients were stage II at diagnosis, and 22% were stage III. About two-thirds of the patients were triple-negative; 93% had nuclear grade III, and 25% had a lymphovascular invasion. Squamous differentiation (29%) was the most common histologic subtype, followed by the spindle subtype (21%). The most common distant metastases were lung (22%), followed by bone (13%). Moreover, 60% had a mastectomy, 19% had endocrine therapy, 58% had radiation, 51% received anthracycline-based chemotherapy, 26% had non-anthracycline chemotherapy, and 22% received no chemotherapy. In the entire cohort, the two-year overall survival (OS) and five-year OS were 79% and 69%, respectively, and the two-year progression-free survival (PFS) and five-year PFS were 72% and 61%, respectively. On multivariable analysis, the stage of MBC (stage III: hazard ratio (HR), 5.065 (95% confidence interval (CI), 1.02-25.27) (p=0.048)), poor functional status (Eastern Cooperative Oncology Group (ECOG) score, 2; HR, 24.736 (95% CI, 1.92-318.73) (p=0.014)), and distant metastasis to the brain (HR, 8.453 (95% CI, 1.88-38.04) (p=0.005)) and lung (HR, 42.102 (95% CI, 7.20-246.36) (p<0.001)) were significant predictors of decreased OS. Conclusions MBC demonstrated early disease progression and poor overall survival. The stage of MBC, decreased performance status, and metastasis to the lung and brain were independent poor prognostic factors.

Spermatic Cord Liposarcoma: A Case Report and Review of the Literature on the Role of Radiotherapy and Chemotherapy in Preventing Locoregional Recurrence.

Spermatic cord cancer is a rare entity. Among malignant tumors of the spermatic cord, liposarcomas are the most common type, often presenting as painless slow-growing masses usually in the fifth and sixth decades of life; they can be misdiagnosed as inguinal hernia or hydrocele. Radical orchiectomy with wide local soft tissue resection is an accepted standard of care for spermatic cord liposarcoma and has been curative in some cases. There is no definitive role for other treatment modalities such as chemotherapy, retroperitoneal lymph node dissection (RPLND), and radiotherapy. We present a case of liposarcoma of the spermatic cord managed with radical orchiectomy, wide local excision, and was followed up without disease recurrence. We also engage in a review of the literature on the role of systemic chemotherapy and radiotherapy in preventing locoregional recurrence after primary surgery. A combination of surgery and postoperative radiotherapy is effective in preventing locoregional spread. Data from case reports support this strategy in certain histologic subtypes or when margins are positive after primary surgery. A follow-up period of up to a decade after surgery is recommended.

A Rare Case of Emphysematous Gastritis Secondary to Chemotherapy.

Emphysematous gastritis is a rare medical condition characterized by the presence of intra-mural air in the stomach associated with portal venous air tracking to a variable degree. There are no established guidelines favoring surgery over medical management. We present a case of a 64-year-old Caucasian male with a history of stage four colon adenocarcinoma with peritoneal carcinomatosis, malignant ascites, and liver metastasis status post-three cycles of chemotherapy who presented to the emergency room with complaints of generalized abdominal pain, nausea, non-bilious vomiting, and melena stools. He was managed conservatively as a case of sepsis secondary to emphysematous gastritis and made a full recovery. To our knowledge, this is the first reported case of emphysematous gastritis in an adult with colon cancer. Although we cannot establish a causal link between his chemotherapy regimen and emphysematous gastritis, the combined effect of an immunosuppressive state caused by advanced malignancy and cytotoxic effects of chemotherapy are the probable risk factors in our patient. We described the possible mechanisms of mucosal disruption by fluorouracil and bevacizumab in our case. Despite historically having a poor prognosis, emphysematous gastritis can be managed conservatively on a case-by-case basis. Clinicians should be aware that chemotherapy can be a predisposing factor to developing this rare condition.

Factors that Minimize Curative Resection for Gallbladder Adenocarcinoma: an Analysis of Clinical Decision-Making and Survival.

BACKGROUND: Gallbladder adenocarcinoma has a poor prognosis as it is often diagnosed incidentally, and patients have a high risk for residual and occult metastatic disease. Expert guidelines recommend definitive surgery for ≥T1b tumors; however, surgical management is inconsistent. This study evaluates the factors that affect the completion of radical resection with portal lymphadenectomy and its impact on survival. METHODS: A retrospective review of patients who underwent surgery for gallbladder cancer from 2008 to 2017 at an academic institution was performed. Patients were analyzed based on whether they underwent definitive surgical resection. Patient factors and clinical decision-making were analyzed; overall survival was compared using Kaplan-Meier analysis. RESULTS: Seventy-five patients with ≥T1b tumors were identified, of who 32 (42.7%) underwent definitive resection. Fifty-four (72%) patients had gallbladder cancer identified as an incidental diagnosis following laparoscopic cholecystectomy. Among patients who did not undergo definitive resection, the underlying factors were varied. Only 24 (55.8%) patients in the non-definitive resection group were seen by surgical oncology. Among patients who underwent re-operation for definitive resection, 12 (38.7%) were upstaged on final pathology. Of the 43 patients who did not undergo definitive resection, 4 (9.3%) had metastatic disease identified during attempted re-resection. Patients who underwent definitive resection had a significantly longer median overall survival compared to those who did not (4.3 v. 1.9 years, p = 0.02). CONCLUSIONS: Patients undergoing definitive resection have a significantly improved survival, including as part of a re-operative strategy. Universal referral to a surgical specialist is a modifiable factor resulting in increased definitive resection rates.