Durvalumab plus gemcitabine and cisplatin in advanced biliary tract cancer: A large real-life worldwide population.

BACKGROUND: The TOPAZ-1 phase III trial showed a survival benefit with durvalumab plus gemcitabine and cisplatin in patients with advanced biliary tract cancer (BTC). To understand this combination's real-world efficacy and tolerability, we conducted a global multicenter retrospective analysis of its first-line treatment outcomes. METHODS: We included patients with unresectable, locally advanced, or metastatic BTC treated with durvalumab, gemcitabine, and cisplatin at 39 sites in 11 countries (Europe, the United States, and Asia). The primary endpoint was overall survival (OS). RESULTS: 666 patients were enrolled. Median OS was 15.1 months and median PFS was 8.2 months. The investigator-assessed overall response rate was 32.7 %, with stable disease in 45.2 % of patients. High baseline CEA levels, ECOG PS > 0, metastatic disease, and NLR > 3 were associated with poor survival. Any grade adverse events (AEs) occurred in 92.9 % of patients (grade >2: 46.6 %). Immune-related AEs (irAEs) occurred in 20.0 % (grade >2: 2.5 %). Three deaths (0.5 %) were deemed treatment-related, none linked to immunotherapy. Common irAEs were rash (8.2 % all grades; 0.3 % grade >2), itching (10.3 % all grades; 0.2 % grade >2), and hypothyroidism (5.1 % all grades; 0.3 % grade >2). Durvalumab discontinuation rate due to AEs was 1.5 %. ESMO-recommended genes were analyzed and no outcome differences were found. A comparative analysis with a historical cohort of patients treated with chemotherapy alone confirmed the positive survival impact of durvalumab in combination with cisplatin/gemcitabine. CONCLUSION: This first global real-world analysis largely confirmed the TOPAZ-1 findings, supporting gemcitabine, cisplatin, and durvalumab as a first-line standard of care for patients with advanced BTC.

Evaluation of the Existence of Post-COVID-19 Tachycardia in a Community Healthcare System.

Background: Post-coronavirus disease 2019 (COVID-19) syndrome derives from lingering symptoms after an acute COVID-19 infection. Palpitation was one of the most common symptoms of post-COVID-19 syndrome that correlated with objective data such as persisting sinus tachycardia; but to our best knowledge, there is a scarcity of research regarding the association of COVID-19 and sinus tachycardia in the post-acute setting. Therefore, the purpose was to identify if there is an association between COVID-19 infection and sinus tachycardia in the post-acute phase, namely post-COVID-19 tachycardia (PCT) other than inappropriate sinus tachycardia (IST) and postural orthostatic tachycardia syndrome (POTS). Methods: This retrospective observational study entails 1,425 patients admitted for COVID-19 infection with the interest in finding an association with PCT. The prevalence of PCT was evaluated using descriptive statistics, predictions of patient characteristics and comorbidities were identified using multinomial logistic regression, and associations between patient comorbidities and characteristics were evaluated with corresponding Pearson Chi-square test and post hoc tests Phi and Cramer's V. Results: The percentage of patients with PCT in our sample of interest was an average of 28.18%. There was a strong association of PCT with patients of age group less than 65 years. Other clinical characteristics, such as shorter length of stay, unknown smoking status, and patients with commercial type insurance, had significant association with PCT. COVID-19 severity categorized as "less severe", readmission rates within 30 days, and patients with less comorbidities were more likely to be associated with PCT. Conclusions: PCT is likely a separate entity from IST and POTS, and an important entity under the umbrella of post-COVID-19 syndrome. It warrants further studies to elucidate the underlying pathophysiology and to confirm its presence as a distinct entity.

Evaluating implementation of NCCN guideline-directed genetic screening recommendations for patients with pancreatic ductal adenocarcinoma.

PURPOSE: In 2019, the National Comprehensive Cancer Network (NCCN) recommended genetic testing for all patients with pancreatic ductal adenocarcinoma (PDAC). To evaluate the status of implementation of these guidelines in a loco-regional setting, we performed a retrospective, observational study among patients with newly diagnosed PDAC who received oncologic care at Northeast Georgia Medical Center in Georgia. METHODS: Chart abstraction of patients with newly diagnosed PDAC from 1 January 2020 to 31 December 2021 was performed to include information on genetic testing recommendation and completion, and time from diagnosis to testing. The deidentified dataset was then analyzed using appropriate descriptive and associative statistical testing. RESULTS: Of the cohort of 109 patients, 32 (29.4%) completed genetic screening; 16 (14.7%) were screened within 10 days of diagnosis. Among the 77 (70.6%) patients who did not receive genetic screening, 45 (41.3%) were not recommended genetic screening despite treatment intent with standard of care therapy. However, 32 (29.4%) were not recommended genetic screening in conjunction with a desire to pursue palliative care/hospice/or due to terminal illness. CONCLUSIONS: The study highlighted the gap in implementation of NCCN guideline-directed genetic testing in PDAC patients as only a third underwent testing suggesting the need for systematic processes to facilitate testing. The test was more likely to be completed if done early in the course, especially soon after the diagnosis. Research is needed to explore discussing genetic testing for the large proportion of patients who are terminally ill at diagnosis where genetic screening would potentially benefit the family members.

A Desmoid Tumor Responding to Systemic Therapy With Tamoxifen and Sulindac.

Desmoid tumors are locally aggressive benign tumors arising from connective tissue and are classified as soft tissue sarcomas that do not metastasize. The name is derived from the Greek word desmos that means tendon-like. These tumors are also known as aggressive fibromatosis and have an unpredictable natural history that varies depending on risk factors. They are treated as sarcomas because of their locally aggressive nature and a high local recurrence rate. The causes behind desmoid tumor development are enigmatic and their clinical course is unpredictable. Disease progression also varies widely depending on multiple syndromic risk factors. At this time, there is no scientific consensus over best treatment practices for this tumor type. Treatment can potentially be a combination of observation, systemic therapy, surgery or radiation therapy. Here, we have described a case of a female patient with a sporadic desmoid tumor that successfully responded to tamoxifen and sulindac.

A Case of Warm Autoimmune Hemolytic Anemia Secondary to Epstein-Barr Virus Infection.

Autoimmune hemolytic anemia (AIHA) is a rare disease characterized by autoantibodies directed at red blood cells. Patients typically present with anemia and are diagnosed by positive direct antiglobulin (DAT) test. AIHA is subclassified into warm or cold based on antibodies involved and depending on their optimal temperature in which they react with RBC antigens. Warm AIHA can be either primary (idiopathic) or secondary depending on etiology. Secondary causes are associated with malignancy, connective tissue and inflammatory diseases, infections (typically viral infections), or drugs (e.g., antibiotics, chemotherapeutic agents). Epstein-Barr virus (EBV) is a herpes virus that is commonly associated with cold AIHA, with only one reported case of EBV-induced warm AIHA. It has been postulated that antibodies against EBV cross-react with antigens expressed on RBC membranes and activate the complement cascade similarly. This case report describes a case of a 32-year-old male who presented with warm AIHA secondary to EBV reinfection.

An Interesting Case Report of Myasthenia Gravis Exacerbation Induced by Durvalumab.

Immune checkpoint inhibitors are novel therapy for a wide range of malignancies. They have been associated with numerous side effects resulting in pulmonary, dermatological, gastrointestinal, and neurological complications. There are few reported cases of myasthenia gravis exacerbation from immune checkpoint inhibitors. We present a case of an 82-year-old woman with a history of myasthenia gravis in remission and non-small cell lung cancer who presented with diplopia, dyspnea, and generalized weakness after three cycles of durvalumab. She was diagnosed with a myasthenic crisis and was treated with high-dose steroids and plasmapheresis.

A Rare Case of Good Outcome of Hodgkin Lymphoma in a Patient with HIV on Antiretroviral Therapy (ART).

BACKGROUND Recent reports have shown an increased incidence of Hodgkin lymphoma (HL) in patients treated with antiretroviral therapy (ART) for human immunodeficiency virus (HIV) infection. This report is of a case of nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) with a good outcome in a 58-year-old Nigerian HIV-positive man who was being treated with ART. CASE REPORT A 58-year-old HIV-positive man presented to a clinic for evaluation of a left axillary mass. He was diagnosed with HIV in 2005, which was well-controlled by ART. He reported intermittent swelling in the left axillary region for several years. Results of a physical examination were significant for mild tender left anterior axillary lymphadenopathy. He had a computed tomography (CT) scan of the chest and neck, which showed left axillary adenopathy, with the largest measuring 3.5×2.0 cm. A staging positron emission tomography-computed tomography (PET/CT) showed focal uptake in 2 left axillary lymph nodes with no other sites involved. He underwent excision of the left axillary lymph node. Histopathology was consistent with nodular lymphocyte-predominant-type Hodgkin's lymphoma (NLHPL). He underwent radiation therapy with a total dose of 3600 centigray (cGy) according to National Comprehensive Cancer Network (NCCN) guidelines. The 5-month follow-up PET/CT scan showed no evidence of malignancy. CONCLUSIONS We present a case of HIV-associated NLHPL that had an indolent course and a good treatment outcome. This case highlights the importance of regular physical examination in HIV patients while on treatment with ART and accurate diagnosis of the cause of lymphadenopathy to prevent extra-nodal spread in cases of lymphoma.

Extremely Aggressive Mesenteric Extragastrointestinal Stromal Tumor: A Case Report and Literature Review.

Gastrointestinal stromal tumors (GISTs) are rare tumors with increasing incidence. GIST is the most common mesenchymal tumor of the gastrointestinal tract involving the elderly population with a slow progression. It originates from the interstitial cells of Cajal. GISTs that develop outside the gastrointestinal tract and have no connections with the intestinal walls or serosal surfaces of the gastrointestinal tubular organs are referred to as extraintestinal gastrointestinal stromal tumors (EGISTs). They have similar morphological and immunohistological characteristics as GISTs. Here, we describe a unique case of an extremely aggressive mesenteric GIST in a 44-year-old African American male. The patient presented to the hospital with complaints of generalized abdominal pain associated with 50-pound weight loss, decreased appetite, and constipation. He underwent computed tomography (CT) of the abdomen and pelvis which showed a large mass along the central mesentery measuring about 15 × 11 cm with adjacent metastatic nodal disease. He underwent a CT-guided biopsy of his abdominal mass with histopathology findings positive for c-kit (CD117) and discovered on GIST-1 (DOG-1) consistent with GIST. Based on TNM staging, his tumor was graded T4 with N1 given nodal involvement placing him as a stage IV. He was referred to an oncologist and was started on neoadjuvant therapy with imatinib. Mesenteric EGISTs, while rare, are known to have a worse prognosis compared to other EGISTs; hence, prompt action must be taken in aggressively treating these tumors. Factors such as mitotic index and tumor size affect the prognosis of mesenteric GISTs.

A Rare Case of Epstein-Barr Virus: Infectious Mononucleosis Complicated by Guillain-Barré Syndrome.

Infectious mononucleosis (IM) is an acute disease caused by Epstein-Barr virus (EBV) infection affecting adolescents and young adults. Clinically, IM presents with fever, lymphadenopathy, and tonsillar pharyngitis. Guillain-Barré syndrome (GBS) has been reported as a possible rare complication of IM. IM-induced GBS is known but rarely reported in the literature. Here, we describe the case of a 19-year-old male with no significant medical history who was diagnosed with GBS following EBV-associated IM. A 19-year-old Caucasian male presented from a referring facility after complaining of generalized weakness involving the upper and lower extremity for about five days. Symptoms began with a sensation of tingling and numbness in the fingertips and toes that progressed over five days to where he was no longer able to ambulate. Physical examination was significant for oropharyngeal exudates, posterior oropharyngeal erythema, tonsillar hypertrophy, cervical lymphadenopathy, flaccid paralysis with areflexia, and paresthesia. Diagnostic workup was consistent with IM and GBS based on cerebrospinal findings. He was subsequently admitted to the intensive care unit, where he received plasmapheresis and intravenous immunoglobulin with significant improvement. This is a rare case of EBV-associated IM GBS. IM is a self-limiting disease but can lead to GBS as one of the known but rare complications. Neurological events have been reported in approximately 2% of patients. Only a few cases of IM leading to GBS have been reported in the literature. Detailed history and physical examination can help identify patients with IM-induced GBS. Moreover, increased awareness can help physicians easily identify and manage GBS, enabling timely recognition and initiation of prompt supportive care to improve recovery time.

A Case of a Mass of the Pancreatic Head Presenting as Mixed Hemorrhagic and Septic Shock.

Acute cholangitis is a biliary tract infection secondary to the obstruction, which causes biliary stasis and bacterial overgrowth. Typically, it presents with the Charcot triad of right upper quadrant abdominal pain, jaundice, and fever. Most acute cholangitis cases are secondary to choledocholithiasis. There are rare cases resulting from pancreatic neoplasm. We report the case of a 43-year-old Caucasian male who was found unresponsive at home with hypotension, anemia, and severe jaundice. Initial imaging studies were notable for a periampullary mass lesion causing intrahepatic biliary ductal dilation. Endoscopic retrograde cholangiopancreatography (ERCP) revealed an actively oozing periampullary fungating mass. In this case, acute cholangitis and hemorrhagic shock secondary to bleeding periampullary lesions are atypical. This case presents an effective treatment plan for this condition.

Diagnostic Dilemma of Paraneoplastic Rheumatic Disorders: Case Series and Narrative Review.

Paraneoplastic rheumatic disorder (RD) is a disorder that may present before, concurrent with, or after the diagnosis of malignancy. Paraneoplastic RDs are a clinical expression of occult cancer that is not directly related to a tumor or metastasis and manifests as rheumatoid symptoms. The RD is determined by the organ system affected by articular, muscular, cutaneous, vascular, or miscellaneous symptoms. Each case is challenging to diagnose because cancer may present with similar symptoms as a common rheumatic disorder. Of note, the majority of cases have minimal responsiveness or no responsiveness to standard rheumatoid treatment. Therefore, it is imperative to recognize and treat the underlying cancer accordingly. Herein, we present four different diagnostic dilemma cases of RD: case #1 - leukocytoclastic vasculitis and C3 glomerulopathy, case #2 - scleroderma, case #3 - Raynaud's syndrome and possible lupus-like syndrome, and case #4 - inflammatory myositis. Institutional IRB approval was obtained for this case series. We will discuss and review the literature on each topic. In addition, we will mention a review of paraneoplastic rheumatoid arthritis. As rheumatic disease is associated with the use of immune checkpoint inhibitors (ICIs) for cancer treatment, we will briefly discuss some of the most common rheumatic presentations in the setting of these drugs. This case review aims to inform clinicians about the atypical presentation of paraneoplastic RD and to highlight the need for interdisciplinary management between rheumatologists, oncologists, and primary care practitioners.