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How to cite this article: Dash S, Pandalanghat S, Kumar Y. An Unusual Case of Hoarseness of Voice and Dysphagia in Multiple Myeloma with Amyloidosis. Indian J Crit Care Med 2024;28(2):175-176.
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Background Prognosis of gallbladder cancer (GBC) has not changed in the past 20 years. Comprehensive genomic profiling (CGP) carries potential to determine the actionability for multiple targets, including ERBB2 , ERBB3 , MET , ROSI , FGFR , and PIK3 . This study evaluates the role of CGP and targeted therapies. Methods This is a multicenter, prospective, single-arm study. All consecutive patients of unresectable and/or metastatic GBC of age ≥18 years were enrolled. Hybrid capture-based CGP was performed by Foundation Medicine CDx. All patients received first-line chemotherapy with gemcitabine-cisplatin regimen. Patients with ERBB2/3 amplification received trastuzumab with capecitabine or nab-paclitaxel, and patients with MET amplification were treated with crizotinib. For ERBB2/3 mutations, lapatinib plus capecitabine regimen was used. Results Fifty patients were studied with a median age of 56 years (range 26-83) and a male-to-female ratio of 1:1.6. ERBB2 and ERBB3 amplification was seen in 9 (18%) and 2 (4%) patients, respectively. Four patients with ERBB2 amplification received trastuzumab and/or lapatinib, showed partial response, and maintained response beyond 12 weeks. One patient had mixed response, whereas two patients progressed on trastuzumab and lapatinib. Three patients with ERBB3 mutations showed response to lapatinib-capecitabine. One patient with MET amplification responded to crizotinib for 4 weeks. PIK3 mutations were present in 14% of cases and were independent of ERBB aberrations. Conclusion GBC is enriched in 28% of patients with ERBB2 and ERBB3 amplifications and/or mutations. Responses are seen with lapatinib in concurrent ERBB2 mutation and amplification. ERBB3 mutation showed response to lapatinib. MET and PIK3 are new findings in GBC, which may be targeted.
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BACKGROUND: Invasive fungal diseases (IFDs) are difficult to diagnose and associated with high mortality rates, especially in the immunosuppressed. Species of Aspergillus and Candida are the cause of majority of invasive fungal disease however IFDs are also caused by Fusarium, Zygomycetes, Trichosporon, etc. Early detection is crucial for appropriate antifungal therapy. Blood cultures usually fail to isolate filamentous fungi, while detection of circulating beta-d-glucan or galactomannan antigens show variable sensitivity and specificity. There is a need of reliable, sensitive and specific diagnostic tests for IFDs. METHODS: A real-time Polymerase Chain Reaction (PCR) assay with a universal primer/molecular beacon system was developed for detecting and speciating most of the pathogenic fungi implicated in IFD. A single-reaction assay was designed targeting a carefully selected region of the ITS2 and ITS5 subunits of the fungal rDNA gene along with four molecular beacons capable of differential hybridization to the amplicons of different species. This generated a signature set of melting temperatures using the standard strains. The assay was tested on clinical specimens from patients with suspected invasive fungal disease. RESULTS: The assay was tested on 72 clinical samples and 72 healthy controls. Of these, 22 clinical samples (6/8 proven; 13/29 probable; 3/35 possible IFD, classified by the EORTC/MSG criteria) were positive by PCR and generated a set of melting temperatures enabling identification of the causative fungus. The assay was negative in all healthy controls. CONCLUSION: The molecular beacon assay is a promising tool providing a rapid method for detection and monitoring of invasive fungal disease in immunosuppressed patients.
