The Outcome of Aplastic Anaemia Associated with Terbinafine Therapy.

Onychomycosis (OM), a widespread fungus that affects the toenails and/or fingernails, causes a large amount of morbidity and is very frequent in the general population. The best treatment is systemic antifungals. Terbinafine is a potent antifungal drug that works by targeting the keratin and lipids found in fungi. In the United States, the prevalence of this nail ailment ranges from 2% to 14%; it is 5.5% globally. Here, we describe a case of aplastic anaemia linked to oral terbinafine use. Clinicians should be aware of this rare adverse effect and early discontinuation of the treatment is required to prevent significant morbidity and mortality. LEARNING POINTS: Aplastic anaemia is a rare side effect of terbinafine.Patients should be advised about this, and serial laboratory testing can be helpful for those who are on a long-term course of terbinafine.Early diagnosis and start of treatment can lead to a favourable outcome.

Autoimmune diabetes from pembrolizumab: A case report and review of literature.

BACKGROUND: Immunotherapy, specifically the use of checkpoint inhibitors such as pembrolizumab, has become an important tool in personalized cancer therapy. These inhibitors target proteins on T-cells that regulate the immune response against tumor cells. Pembrolizumab, which targets the programmed cell death 1 receptor on T-cells, has been approved for the treatment of metastatic melanoma and non-small cell lung cancer. However, it can also lead to immune-related side effects, including pneumonitis, colitis, thyroid abnormalities, and rare cases of type 1 diabetes. CASE SUMMARY: The case presented involves an adult patient in 30s with breast cancer who developed hyperglycemia after receiving pembrolizumab treatment. The patient was diagnosed with diabetic ketoacidosis and further investigations were performed to evaluate for new-onset type 1 diabetes. The patient had a history of hypothyroidism and a family history of breast cancer. Treatment for diabetic ketoacidosis was initiated, and the patient was discharged for close follow-up with an endocrinologist. CONCLUSION: This literature review highlights the occurrence of diabetic ketoacidosis and new-onset type 1 diabetes in patients receiving pembrolizumab treatment for different types of cancer. Overall, the article emphasizes the therapeutic benefits of immunotherapy in cancer treatment, particularly pembrolizumab, while also highlighting the potential side effect of immune-related diabetes that can occur in a small percentage of patients. Here we present a case where pembrolizumab lead to development of diabetes after a few cycles highlighting one of the rare yet a serious toxicity of the drug.

Calcitriol induced hypercalcemia - a rare phenomenon in lung cancer: A case report.

BACKGROUND: Calcitriol-induced hypercalcemia has been rarely reported in cases of lung cancer; however, it is frequently reported in cases of lymphoid malignancy and granulomatous disease. We present a rare case of hypercalcemia associated with squamous cell cancer of the lung with elevated calcitriol level. CASE SUMMARY: A 61-year-old Caucasian female with severe hypercalcemia of 15 mg/dL, which led to a new diagnosis of metastatic lung cancer. Since the parathyroid hormone-related peptide (PTHrP) level was minimally elevated at 2.1 pmol/L, we believe excessive calcitriol production by tumor cells was the underlying mechanism for hypercalcemia. Calcitriol was significantly elevated at 130 pg/mL with a low 25-hydroxyvitamin D level of 25.9 ng/mL and suppressed PTH level of 8 pg/mL. Corticosteroids are generally used to treat calcitriol-induced hypercalcemia, but we successfully treated our patient with bisphosphonate, highlighting the further utility of bisphosphonates in hypercalcemia treatment. CONCLUSION: We believe that the underlying cause of hypercalcemia, in this case of metastatic squamous cell lung carcinoma, was elevated calcitriol, which was likely produced by the tumor cells. In addition to PTHrP, calcitriol levels should be included in the workup for hypercalcemia in cases of lung cancer. However, the pathophysiology and prognostic significance of dysregulated calcitriol production in solid tumors remain unclear and warrant further research. Bisphosphonate may be used as a steroid-sparing therapy even in cases of calcitriol-induced hypercalcemia and warrants further investigation.

When Hormones are Being Difficult: A Rare Case and the Literature Review of Pembrolizumab-Induced Polyendocrinopathy.

Immune Checkpoint inhibitors (ICIs) such as nivolumab, pembrolizumab, and ipilimumab are monoclonal antibodies against cytotoxic T lymphocyte antigen 4 (CTLA4) or program death (PD)1 and its ligand PDL1. Agents targeting PD1, such as pembrolizumab, have shown widespread efficacy in the past and are also associated with a wide range of immune-related adverse events (irAEs), including endocrine toxicities. A 31-year-old female with a medical history significant for Stage IIb Breast cancer on chemo and immunotherapy (pembrolizumab) presented with nausea, vomiting, and generalized abdominal pain. Laboratory studies showed a blood glucose level of 356 mg/dl, elevated Anion gap 18 meq/L, beta-hydroxybutyrate 46 mg/d, and low C-peptide levels <0.10 ng/ml. The patient was treated for Diabetic Ketoacidosis (DKA). Further testing revealed high Thyroid Stimulating Hormone (TSH) levels along with elevated thyroid peroxidase levels of 38 IU/L. After discharge from the hospital on insulin and levothyroxine therapy, the patient reported increasing fatigue and further testing revealed low cortisol levels <0.5 mcg/dl with elevated ACTH consistent with primary adrenal insufficiency. The patient was started on hydrocortisone therapy with improvement in symptoms. Endocrine toxicities are not uncommon in patients receiving pembrolizumab, but polyendocrinopathy in a relatively rare side effect of pembrolizumab. Only a few cases of pembrolizumab-induced polyendocrinopathy have been reported so far which we have mentioned in this article. While patients are on immunotherapy, close monitoring for clinical signs & symptoms can lead to an early diagnosis, substantially improving morbidity and mortality.

Epidemiology and Determinants of Survival for Primary Intestinal Non-Hodgkin Lymphoma: A Population-Based Study.

Background: Gastrointestinal tract is the most common site of extranodal non-Hodgkin lymphoma (EN-NHL). Most of the published data have been on gastric NHL with limited studies on primary intestinal non-Hodgkin lymphoma (PI-NHL) considering rare incidence. We performed epidemiological and survival analysis for PI-NHL from the Surveillance, Epidemiology, and End Results (SEER) 18 database. Methods: A total of 9,143 PI-NHL cases of age ≥ 18 years were identified from the SEER 18 database for the period 2000 - 2015. Totally, 8,568 patients were included for survival analysis. Cause-specific survival (CSS) and overall survival (OS) analysis were done for PI-NHL and PI-diffuse large B-cell lymphoma (PI-DLBCL) using sex, age of onset, treatment, histology, stage, and year of diagnosis. Survival analysis was done by using Cox proportional hazard model and Kaplan-Meier plot with log-rank test. Results: The percentage of PI-NHL of all the intestinal cancers and EN-NHL were 1.35%, and 10.52%, respectively. The age-adjusted incidence was 0.9145/100,000 population for the study population. PI-NHL was more common among patients aged ≥ 60 years, male and non-Hispanics Whites. Majority of patients were diagnosed at stage 1 and 2 (74%), and DLBCL (44.8%) was the most common histology. Overall median survival was 111 (95% confidence interval (CI): 105 - 117) months. In OS analysis, significant increased risk of mortality was seen with T-cell NHLs vs. DLBCL (hazard ratio (HR): 2.56), patients aged ≥ 60 vs. < 60 years (HR: 2.87), stage 4 vs. stage 1 (HR: 1.93), male vs. female (HR: 1.17), with best outcome seen in patient treated with combination of chemotherapy and surgery vs. none (HR: 0.45). Similar results were seen in CSS and for PI-DLBCL as well. Significant improvement in outcomes was observed for PI-DLBCL patients receiving chemotherapy with/without surgery. Conclusions: Findings from our large, population-based study reveal PI-NHL is a rare type of intestinal malignancy with significant difference in survival based on histological and epidemiological characteristics.

Site-Specific Survival of Extra Nodal Diffuse Large B-Cell Lymphoma and Comparison With Gastrointestinal Diffuse Large B-Cell Lymphoma.

Background: Diffuse large B-cell lymphoma (DLBCL) constitutes 30% of all non-Hodgkin's lymphomas. It can present as a nodal disease or as an extra nodal disease. Based on the site of origin, extra nodal DLBCL (EN-DLBCL) may have a distinct clinical outcome. Apart from the site of origin, factors including demographics, stage, and presence of any other primary malignancy also affect the outcome. The purpose of our study was to characterize prognostically distinct groups based on the site of presentation of EN-DLBCL. Methods: We used 18 registries in Surveillance, Epidemiology, and End Results database to identify the patients with EN-DLBCL for 2000 - 2015 with last follow-up till December 31, 2018. A total of 30,290 EN-DLBCL patients were selected and categorized based on 13 broad sites grouping. Demographic variables were summarized. We did overall survival analysis with univariate and multivariate Cox-proportional hazard modeling. Short-term survival trend was calculated as well. Results: The percentage of EN-DLBCL of all DLBCLs is 34.48%. EN-DLBCL was comparatively seen more in males (54.94%) and non-Hispanic whites (71.52%). In terms of clinical characteristics, patients with EN-DLBCL were mostly diagnosed at age ≥ 60 years (66.11%), early stage (69.33%), and presentation as first primary cancer (81.89%). A higher risk of mortality was seen in non-Hispanic black (hazard ratio (HR) 1.36), with late age of onset (HR 2.69), late stage at presentation (HR 1.42), and with history of other malignancy (HR 1.29). Compared to the intestinal tract, the risk of overall mortality was higher in individuals with involvement of nervous system (HR 1.85), pancreas and hepatobiliary system (HR 1.22), and respiratory system (HR 1.18) and the best outcomes were seen in heart and mediastinal site (HR 0.58) of DLBCL. Conclusion: Based upon our population-based study, we conclude that primary site of presentation of EN-DLBCL is an important prognostic factor with significant difference in survival based on histological and epidemiological characteristics.

Dysphagia as a Rare Presentation of Cervical Cancer with Mediastinal Metastasis.

Dysphagia has a broad aetiology and so it is essential to identify the precise cause. Cervical cancer metastasis is distinctive in that it usually involves local lymph node invasion; however, approximately 1% of cases have mediastinal involvement, which can cause severe compressive symptoms in rare situations. To highlight an uncommon severe manifestation of cervical cancer relapse, we describe a case of dysphagia in a woman with a history of cervical cancer. After a thorough investigation that included endoscopy, endoscopy with ultrasound, an oesophagogram and fine needle aspiration, we eventually reached the diagnosis of mediastinal metastatic cervical cancer. Following interventions, the patient's condition gradually improved, both clinically and radiographically. LEARNING POINTS: Mediastinal lymph node enlargement causing dysphagia can be a presenting sign of a metastatic lesion from treated cervical cancer.A PEG tube is helpful in relieving dysphagia caused by metastatic mediastinal lymph node enlargement and as bridge for nutrition during chemotherapy.The VEGF inhibitor bevacizumab can be used in advanced metastatic cervical cancer.Check-point inhibitors like pembrolizumab can be used in metastatic cervical cancer.

The prevalence of asymptomatic COVID-19 infection in cancer patients. A cross-sectional study at a tertiary cancer center in New York City.

OBJECTIVE: Several factors raise concern for increased risk of COVID-19 in cancer patients. While there is strong support for testing symptomatic patients. The benefit of routine testing of asymptomatic patients remains contentious. We aim to evaluate the prevalence of asymptomatic COVID-19 infection in cancer patients. METHODS: Between June 1 and September 3, 2020, we obtained nasopharyngeal swab from asymptomatic cancer patients who were visiting a single tertiary-care cancer center, and tested the specimen for the presence or absence of SARS-CoV-2 RNA. We performed a descriptive statistic of data RESULTS: We tested a total of 80 patients, of which 3 (3.75%) were found positive for COVID-19. A significant proportion of the tested patients were on active immunosuppressive or immunomodulatory treatment, cytotoxic chemotherapy (n = 34), and immunotherapy (n = 16). However, all three COVID-19 positive patients were only actively on hormonal therapy. All three patients observed a minimum of 2 weeks home quarantine. None of the patients developed symptoms upon follow up and no changes were required to their treatment plan. CONCLUSIONS: Despite published evidence that cancer patients may be at increased risk of severe COVID -19 infection, our data suggest that some infected cancer patients are asymptomatic. The overall prevalence of asymptomatic COVID-19 infection in this population of cancer patients was similar to that in the general population. Therefore, since asymptomatic infections are not uncommon in patients with cancer, we recommend universal COVID-19 testing to help guide treatment decisions and prevent the spread of the disease.

Clinical Determinants Differentiating the Severity of SARS-CoV-2 Infection in Cancer Patients: Hospital Care or Home Recovery.

Background: Cancer patients may carry a worse prognosis with SARS-CoV-2 infection. Most of the previous studies described the outcomes of hospitalized cancer patients. We aimed to study the clinical factors differentiating patients requiring hospital care vs. home recovery, and the trajectory of their anti-cancer treatment. Methods: This study was conducted in a community cancer center in New York City. Eligible patients were those who had cancer history and were diagnosed of SARS-CoV-2 infection between March 1 and May 30, 2020, with confirmatory SARs-CoV-2 virus test or antibody test. Four groups were constructed: (A) hospitalized and survived, (B) hospitalized requiring intubation and/or deceased, (C) non-hospitalized, asymptomatic, with suspicious CT image findings, close exposure, or positive antibody test, and (D) non-hospitalized and symptomatic. Results: One hundred and six patients were included in the analysis. Thirty-five patients (33.0%) required hospitalization and 13 (12.3%) died. Thirty (28.3%) patients were asymptomatic and 41 (38.7%) were symptomatic and recovered at home. Comparing to patients who recovered at home, hospitalized patients were composed of older patients (median age 71 vs. 63 years old, p = 0.000299), more who received negative impact treatment (62.9 vs. 32.4%, p = 0.0036) that mostly represented myelosuppressive chemotherapy (45.7 vs. 23.9%, p = 0.0275), and more patients with poorer baseline performance status (PS ≥ 2 25.7 vs. 2.8%, p = 0.0007). Hypoxemia (35% in group A vs. 73.3% in group B, p = 0.0271) at presentation was significant to predict mortality in hospitalized patients. The median cumulative hospital stay for discharged patients was 16 days (range 5-60). The median duration of persistent positivity of SARS-CoV-2 RNA was 28 days (range 10-86). About 52.9% of patients who survived hospitalization and required anti-cancer treatment reinitiated therapy. Ninety-two percent of the asymptomatic patients and 51.7% of the symptomatic patients who recovered at home continued treatment on schedule and almost all reinitiated treatment after recovery. Conclusions: Cancer patients may have a more severe status of SARS-CoV-2 infection after receiving myelosuppressive chemotherapy. Avoidance should be considered in older patients with poor performance status. More than two thirds of patients exhibit minimal to moderate symptoms, and many of them can continue or restart their anti-cancer treatment upon recovery.

Chemotherapy Treatment Modifications During the COVID-19 Outbreak at a Community Cancer Center in New York City.

PURPOSE: As a result of their immunocompromised status associated with disease and treatment, patients with cancer face a profound threat for higher rates of complications and mortality if they contract the coronavirus disease 2019 infection. Medical oncology communities have developed treatment modifications to balance the risk of contracting the virus with the benefit of improving cancer-related outcomes. METHODS: We systemically examined our community cancer center database to display patterns of change and to unveil factors that have been considered with each decision. We studied a cohort of 282 patients receiving treatment and found that 159 patients (56.4%) had treatment modifications. RESULTS: The incidence of treatment modification was observed in patients undergoing adjuvant and neoadjuvant (41.4%), palliative (62.9%), or injectable endocrine or bone-modulating only (76.0%) treatments. Modifications were applied to regimens with myelosuppressive (56.5%), immunosuppressive (69.2%), and immunomodulating (61.5%) potentials. These modifications also affected intravenous (54.9%) and subcutaneous injectable treatments (62.5%) more than oral treatments (15.8%). Treatment modifications in 112 patients (70.4%) were recommended by providers, and 47 (29.6%) were initiated by patients. The most common strategy of modification was to skip or postpone a scheduled treatment (49%). Among treatment with no modifications, treatment regimens were maintained in patients who tolerated treatment well (37.0%), in treatments with curative intent (22%), and in symptomatic patients who required treatment (14%). CONCLUSION: Our observation and analysis suggested that the primary goal of treatment modification was to decrease potential exposure. The pattern also reflected the negative impact of the pandemic on health care providers who initiated these changes. Providers have to consider individualized recommendations incorporating multiple factors, such as tolerance, potential toxicity, treatment nature and route, and disease severity.

Clinical benefit and tolerability of adjuvant intraperitoneal chemotherapy in patients who have or have not received neoadjuvant chemotherapy for advanced ovarian cancer.

BACKGROUND: Adjuvant chemotherapy using intraperitoneal (IP) treatment has demonstrated survival benefit over intravenous (IV) therapy alone in patients treated with upfront debulking surgery for advanced stage ovarian cancer. Neoadjuvant chemotherapy followed by interim surgery and adjuvant chemotherapy has similar outcome in survival as compared to upfront surgery followed by adjuvant IV chemotherapy. IP chemotherapy has not been widely adopted in clinical practice for a number of reasons. Whether IP chemotherapy delivered in the patients who received neoadjuvant chemotherapy can be well tolerated or confers any clinical benefit has not been well studied. AIM: To evaluate the experience of adjuvant IP chemotherapy in the community cancer clinic setting, and the clinical benefit and tolerability of incorporating IP chemotherapy in patients who received neoadjuvant treatment. METHODS: We retrospectively evaluated toxicities and outcomes of patients with stage III and IV ovarian cancer diagnosed at our institution between 07/2007 and 07/2015 who received intraperitoneal chemotherapy after cytoreductive surgery (group 1) or after neoadjuvant chemotherapy followed by interim surgery (group 2). RESULTS: Thirty eight patients were treated with IP chemotherapy, median age was 54 years old (range 38.6 to 71 years). In group 1 (n = 25), 12 (48%) of the patients completed 4 or more cycle of IP treatment after upfront debulking surgery; while in group 2 (n = 13), 8 (61.5%) of the patients completed all 3 cycles of the assigned IP chemotherapy after receiving neoadjuvant IV chemotherapy followed by surgery, and 2 (15.4%) more patients tolerated more than 3 cycles. In those patients who did not get planned IP chemotherapy, most of them were treated with substitutional IV chemotherapy, and the completion rate for 6 cycles of IV + IP was 92%. Abdominal pain, (64% in group 1 and 38% in group 2), vomiting, (36% in group 1 and 30.8% in group 2), dehydration (16% in group 1 and 15.4% in group 2), and hypomagnesemia (12% in group 1 and 15.4% in group 2) were the most common adverse effects in all patients, while patients who have received neoadjuvant chemotherapy were more likely to get hypokalemia, fatigue and renal insufficiency. Progression free survival (PFS) was 26.5 mo (95% CI 14.9, 38.0) in group 1 and 27.6 mo (95% CI 13.1, 42.1) in group 2. The overall survival was 100.2 mo (95% CI 67.9, 132.5) for group 1 and 68.2 mo (95% CI 32.2, 104.0) for group 2. For the entire cohort, PFS was 26.5 mo (95% CI 15.9, 37.0) and OS was 78.8 mo (95% CI 52.3, 105.4). CONCLUSION: The use of IP/IV chemotherapy can be safely administrated in the community cancer clinic setting. The use of IP/IV chemotherapy in patients who have received neoadjuvant chemotherapy followed by surgery is feasible and tolerable. Despite various modification of the IP regimen, incorporation of IP chemotherapy in the adjuvant setting appears to be associated with improved PFS and overall survival.

A Comparative Study of Primary Adenoid Cystic and Mucoepidermoid Carcinoma of Lung.

BACKGROUND: Pulmonary mucoepidermoid carcinoma (PMEC) and pulmonary adenoid cystic carcinoma (PACC) are the two major types of primary salivary gland-type (PSGT) lung cancers. The demographic profile, clinicopathological features, and predictors of survival as an overall group have not been described for PSGT cancers of lung. METHODS: In this study, we analyzed demographic, clinical, and survival data from 1,032 patients (546 PMEC and 486 PACC) who were diagnosed of PSGT lung cancer in the Surveillance, Epidemiology and End Results database from 1973 to 2014. RESULTS: The PSGT constituted 0.09% of all lung cancers with age-adjusted incidence rate of 0.07 per 100,000 person-years and change of -32% from 1973 to 2014. The incidence of PMEC was slightly higher than PACC but there were no differences in the age and sex distribution. PACCs (55%) were significantly higher at trachea and main bronchus while PMECs were more common at peripheral lungs (85%). Most of the tumors were diagnosed at an early stage and were low grade irrespective of histology. As compared to PMEC, significantly higher number of patients with PACC underwent radical surgery and received adjuvant radiation. The 1- and 5-year cause-specific survival was 76.6 and 62.8%, respectively. On multivariate analysis, the survival was affected by age at diagnosis, tumor stage, histological grade, period of diagnosis, and surgical resection. The histology showed strong interaction with time and hazard ratio of patients with PACC was significantly worse than patients with PMEC only after 5 years. CONCLUSION: The incidence of pulmonary PSGT cancer is 7 cases per 10 million population in the United States and is decreasing. There was no difference between demographic profile of patients with PMEC and PACC but pathological features were diverse. The difference in the survival of patients with the two histological types surfaced only after 5 years when survival of patients with PMEC was better than PACC.

Systemic Cystic Angiomatosis Mimicking Metastatic Cancer: A Case Report and Review of the Literature.

Systemic cystic angiomatosis is a rare benign disorder due to the maldeveloped vascular and lymphatic system with less than 50 cases reported in literature so far. We report here a case of systemic cystic angiomatosis (SCA) with multisystem involvement affecting the neck, thyroid, thoracic cavity, and skeletal system. The patient initially presented in her 4th decade of life with isolated lymphangioma in the neck requiring surgery. However, she experienced full-blown manifestations of SCA in her 6th decade which closely mimicked metastatic cancer. The diagnosis of SCA could only be established after multiple biopsies. The radiological and histological features of SCA with its course over 31 years in this patient have been described.