Parita Soni

Current Diagnosis and Management of Immune Related Adverse Events (irAEs) Induced by Immune Checkpoint Inhibitor Therapy

The indications of immune checkpoint inhibitors (ICIs) are set to rise further with the approval of newer agent like atezolimumab for use in patients with advanced stage urothelial carcinoma. More frequent use of ICIs has improved our understanding of their unique side effects, which are known as immune-related adverse events (irAEs). The spectrum of irAEs has expanded beyond more common manifestations such as dermatological, gastrointestinal and endocrine effects to rarer presentations involving nervous, hematopoietic and urinary systems. There are new safety data accumulating on ICIs in patients with previously diagnosed autoimmune conditions. It is challenging for clinicians to continuously update their working knowledge to diagnose and manage these events successfully. If diagnosed timely, the majority of events are completely reversible, and temporary immunosuppression with glucocorticoids, infliximab or other agents is warranted only in the most severe grade illnesses. The same principles of management will possibly apply as newer anti- cytotoxic T lymphocytes-associated antigen 4 (CTLA-4) and programmed cell death protein 1 (PD-1/PD-L1) antibodies are introduced. The current focus of research is for prophylaxis and for biomarkers to predict the onset of these toxicities. In this review we summarize the irAEs of ICIs and emphasize their growing spectrum and their management algorithms, to update oncology practitioners.

Kaposi Sarcoma Mimicking Acute Flare of Ulcerative Colitis

Besides an AIDS-defining illness, Kaposi sarcoma (KS) is also seen in individuals on long-term immunosuppressant therapy. We report KS in a 70-year-old immunocompetent man, which initially mimicked acute flare of ulcerative colitis (UC). He was hospitalized multiple times for complaints of watery diarrhea and tenesmus. Despite treatment with mesalamine, short courses of methylprednisolone, and one dose of infliximab, his symptoms improved only partially. He underwent colonoscopy, which revealed mild active colitis and a mass in the ascending colon. After treatment of acute flare with methylprednisone and mesalamine, he underwent total colectomy with end ileostomy. The histopathology confirmed stage I adenocarcinoma of colon. He continued to experience watery diarrhea, which was attributed to intractable UC, and he underwent protectomy several weeks later. The histopathology of rectum revealed KS. After surgery, watery diarrhea resolved completely. Review of literature suggests KS has been rarely reported in immunocompetent individuals with inflammatory bowel disease.

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.

Unusual Presentation of Diffuse Large B-Cell Lymphoma With Splenic Infarcts:

A 67-year-old man presented with a 3-day history of abdominal pain, fever, and significant weight loss over 2 months. Physical examination revealed left upper quadrant tenderness, hepatomegaly, splenomegaly, and bilateral pitting edema but peripheral lymphadenopathy was absent. Laboratory tests showed anemia, thrombocytopenia, elevated prothrombin time (PT), partial thromboplastin time (PTT), and increased lactate dehydrogenase (LDH). PTT was corrected completely in mixing study. Further workup for the cause of coagulopathy revealed decreased levels of all clotting factors except factor VIII and increase fibrinogen levels, which ruled out disseminated intravascular coagulation (DIC). Flow cytometry of peripheral blood was normal. Contrast-enhanced computed tomography (CECT) revealed splenomegaly with multiple splenic infarcts without any mediastinal or intraabdominal lymphadenopathy. Further investigations for infective endocarditis (blood cultures and transthoracic echocardiography) and autoimmune disorders (ANA, dsDNA, RA factors) were negative. The patient received treatment for sepsis empirically without any significant clinical improvement. The diagnosis remained unclear despite extensive workup and liver biopsy was conducted due to high suspicion of granulomatous diseases. However, the liver biopsy revealed high-grade diffuse large B-cell lymphoma (DLBCL). Unfortunately, patient died shortly after the diagnosis. Here we report a case of high-grade DLBCL with hepatosplenomegaly and splenic infarcts in the absence of any lymphadenopathy or focal lesions. This case highlights the fact that unusually lymphoma can present in the absence of lymphadenopathy or mass lesion mimicking autoimmune and granulomatous disorders. The diagnosis in these cases can only be made on histology, and hence the threshold for biopsy should be low in patients with unclear presentations and multiorgan involvement.

Emerging Therapies in the Management of Advanced-Stage Gastric Cancer

Globally, gastric malignancy contributes to significant cancer-related morbidity and mortality. Despite a recent approval of two targeted agents, trastuzumab and ramucirumab, the treatment options for advanced-stage gastric cancer are limited. Consequently, the overall clinical outcomes for patients with advanced-stage gastric cancer remain poor. Numerous agents that are active against novel targets have been evaluated in the course of randomized trials; however, most have produced disappointing results because of the molecular heterogeneity of gastric cancer. The Cancer Genome Atlas (TCGA) project proposed a new classification system for gastric cancer that includes four different tumor subtypes based on molecular characteristics. This change led to the identification of several distinct and potentially targetable pathways. However, most agents targeting these pathways do not elicit any meaningful clinical benefit when employed for the treatment of advanced-stage gastric cancer. Most advanced-stage gastric cancer trials currently focus on agents that modulate tumor microenvironments and cancer cell stemness. In this review, we summarize data regarding novel compounds that have shown efficacy in early phase studies and show promise as effective therapeutic agents, with special emphasis on those for which phase III trials are either planned or underway.

122: EBSTENOID ANOMALY

Learning Objectives: To investigate the learning curve of transesophageal echocardiography (TEE) applied in mechanically ventilated patients in ICU. Methods: A prospective observation study was conducted. A total of 60 consecutive patients with TEE examination admitted to Department of SICU of First Affiliated Hospital of Sun Yat-Sen University from December 2016 to June 2017 were enrolled. According to the date of TEE examination, the patients were divided into five groups(A, B, C, D, E), with 12 patients in each group.The TEE examination scores,duration and complication among five groups were compared, with learning curve established. The examination scores including the quality of the 20-TEE views, color doppler flow imaging and hemodynamics were assessed by TEE expert. Results: There were no significant differences in gender composition, age, acute physiology and chronic health evaluation II (APACH II), primary disease and prognosis among five groups, which showed the baseline was equivalent and comparable. There were statistically significant differences in TEE examination scores (F = 15.934, P = 0.000) and duration (F = 16.011, P = 0.000) among five groups. The examination scores of group A and group B were (23.67 ± 9.70) and (30.00 ± 11.42) respectively (P > 0.05), while the scores of group C, group D and group E were (40.08 ± 7.27), (41.75 ± 5.62) and (46.17 ± 3.41) respectively (P> 0.05). The scores of group A and group B were significantly lower than that of group C, D and E(P < 0.05). The learning curve showed an upward trend, and the scores gradually tended to be stable after the group C. The examination duration of group A [(58.22 ± 14.19)min] was the longest and fluctuated most(P < 0.05).The duration of group B and group C was (43.33 ± 4.64) min and (39.97 ± 6.67) min respectively (P > 0.05), while the duration of group D and group E was (31.04 ± 7.84) min and (31.50 ± 4.82) min respectively (P > 0.05). The examination duration of group A,B and C were significantly longer than that of group D and group E (P < 0.05). The learning curve showed a downward trend, and the duration was stable after group D. There were no significant differences in complications of TEE examination among five groups (P> 0.05). Conclusions: The learning curve of performing TEE examination is approximately 36-48 cases for mechanically ventilated patients in ICU. With the completion of 36 performances, one can basically grasp this technique, and may reach full mastery after 48 performances.

Chronic Lymphocytic Leukemia: A Rare Cause of Pathological Fracture of the Femur

The incidence rate of chronic lymphocytic leukemia (CLL) in the United States is approximately 0.005%; men are at slightly higher risk than women. Bony involvement or pathological fracture rarely occurs in CLL, and it may be the initial presentation. An 85-year-old woman presented with acute respiratory failure secondary to pneumonia. Symptomatology included dyspnea. She was found to have pathological fracture of the femur caused by CLL. The diagnosis of CLL had been made 6 years previously, but the patient had refused therapy. On admission, the patient required endotracheal intubation, mechanical ventilation, and admission to the medical intensive care unit. Endotracheal intubation extubation was successful after 48 hours. The patient then complained of severe left knee pain. Bone radiograph and femoral computed tomography scan revealed acute pathological fracture of the left distal femur. There was no history of trauma. The fracture was stabilized with extension lock splint. Pathological fracture in patients with CLL is associated with hypercalcemia, Richter’s transformation, or multiple myeloma. This patient exemplifies the fact that pathological fracture can be caused by CLL in the absence of hypercalcemia, Richter’s transformation, or multiple myeloma and can be the initial presentation of CLL.

Enterovirus-Human Rhinovirus: A Rare Cause of Acute Respiratory Distress Syndrome:

A 22-year-old Asian woman presented with respiratory distress, cough, and wheezing for 1 week. Prior history included asthma and Turner syndrome. On presentation to the emergency department, the patient was hypotensive, tachycardic, tachypneic, with an oxyhemoglobin saturation in the mid 80% range while breathing ambient air. Chest radiograph revealed pulmonary vascular congestion and a left lower lobe infiltrate. Endotracheal intubation, mechanical ventilation, and vasopressors were initiated. Empiric therapy for community-acquired pneumonia was administered utilizing broad-spectrum intravenous antibiotics. Routine sputum culture was negative for pathogens. Nasopharyngeal swab submitted for multiplex amplified nucleic acid testing yielded enterovirus-human rhinovirus (EV-HRV). Thus, the diagnosis of EV-HRV pneumonia complicated by acute respiratory distress syndrome (ARDS) was established. Multiple attempts to wean from the ventilator were unsuccessful, and a tracheostomy was performed. This report highlights EV-HRV as a cause of severe ARDS and prolonged respiratory failure in adults.

Authenticity and Reliability of the Cardiac Monitor Alarms in the ICU: A Patient Safety Concern Due to Alarm Fatigue

PURPOSE: It is desirable for the cardiac monitor (CM) to have a high sensitivity. Frequent alarms may cause alarm fatigue of the medical personnel leading to delayed or no response to the alarms, which could jeopardize patient’s safety. The impact of following standard processes/protocols such as pertinent skin preparation, changing electrocardiogram (EKG) leads daily, customization of alarm parameters, and education of the nursing staff to reduce the false alarms remains unclear. The aim of this study was to analyze the accuracy of the CM alarms in the intensive care unit (ICU) with utilization of the standard protocol.

Penoscrotal haematoma after cardiac catheterisation

Scrotal haematoma is an extremely rare complication after cardiac catheterisation (CC) with only few cases reported in literature. We report a 56-year-old patient who developed large scrotal haematoma after CC via transfemoral approach requiring blood transfusion due to haemodynamic instability. After an uneventful elective procedure, he was discharged with a collagen plug-based vascular closure device (Angio-Seal). He developed sudden onset, excruciating groin pain with scrotal swelling and shock. Bleeding was stopped with manual compression over the femoral artery and 2 units of packed red blood cells were transfused. CT angiogram revealed scrotal haematoma without active bleeding. Testicular blood supply remained intact. Scrotal swelling improved with conservative management and patient got discharged 3 days later in a stable condition. The review of literature suggests that penoscrotal haematoma is unusual after CC but may result from arterial injury or bleeding into the fascial planes. Majority of patients require observation but surgery is indicated in selected cases for vascular complications.