Ciprofloxacin is a commonly used antibiotic for gastrointestinal and genitourinary tract infections with a considerably good safety profile. However, occasionally it may cause life-threatening complications. Two case reports of bone marrow depression and 1 case of thrombocytopenia due to ciprofloxacin therapy have been reported in literature. We report a case of bone marrow depression due to ciprofloxacin therapy for urinary tract infection in an otherwise healthy woman.
Background Coupling devices have become commonplace in performing venous anastomoses during microvascular free tissue transfer (FTT). However, arterial anastomoses are still most commonly performed using traditional microvascular suture techniques. Objective To describe the safety and feasibility of using microvascular coupling devices for free flap arterial anastomosis. Methods A systematic review of English language literature was performed for studies that investigated the use of an arterial coupler for microvascular FTT in human patients. A comprehensive search of MEDLINE (January 1948 to August 2018), EMBASE (January 1974 to August 2018), and Web of Science was performed. Results Fifteen studies were included. All studies were retrospective case series. A combined total of 395 arterial anastomoses were attempted with a coupling device. All studies except for one used the 3M Unilink/Synovis coupling device. One study used a novel absorbable coupling device. The coupling device was aborted and converted to a suture technique in 8.4% of attempted anastomoses. Rupture of the anastomotic device was reported in only 1 patient (0.3%). Thrombosis was also infrequent at 1.9%. The quality assessment showed a high risk of bias in all studies. Conclusion In selected patients, coupling devices for arterial anastomoses have a good success rate with low rates of thrombosis based on limited quality evidence.
Background The American Joint Committee on Cancer (AJCC) released a new staging system for human papilloma virus (HPV) positive oropharyngeal cancer (OPC) in their eighth edition. The role of smoking in HPV positive oropharyngeal cancer remains controversial and is not factored into the updated staging system. Methods Single institutional, retrospective chart review of patients with HPV positive OPC from 2009 to 2017 was completed. Dichotomized smoking data were collected into 0–9 and ≥10 pack‐year histories. Kaplan–Meier survival curves compared overall survival (OS) for smokers and nonsmokers. Results Five‐year OS was not statistically different in stage I or stage II HPV positive OPC comparing nonsmokers versus smokers, but worse in stage III smokers (38% vs. 76%, p < 0.05). Conclusion Greater than 10 pack‐year smoking status may negatively affect survival in late stage HPV positive OPC but not in early stage disease. HPV positive smokers may require additional risk stratification.
Introduction/Objective The anaplastic lymphoma kinase (ALK) gene is a receptor tyrosine kinase gene located in the 2p23.2 region. Normally, dimerization of ALK receptor by binding to its ligand activates the ALK receptor by autophosphorylation of c-termius and activates downstream PI3K, MAPK and JAK3 pathways. The ALK gene is abnormally hyperactivated by fusion of the 3’ half containing the kinase domain with 5’ portion of other genes, resulting in the ligand independent dimerization and activation of the ALK receptor. The tumors harboring these translocations are termed as ALK-positive tumors and can be treated with ALK inhibitors. Methods We analyzed the status of clinically relevant ALK fusion driver mutations in 230 different cancer studies, containing tumors from 79222 different individuals, in The Cancer Genome Atlas database (TCGA) using the cbioportal web browser. Results We observed that, as expected ALK-positive mutations are predominantly present in NSCLC, with EML4- ALK being the most common. In addition, we were able to identify ALK positive mutations in colorectal carcinomas, papillary thyroid carcinomas, papillary renal cell carcinomas, sarcomas and invasive ductal carcinomas of the breast. Most important, our analysis identified extremely rare ALK positive cases in salivary duct carcinomas, urothelial carcinomas, cutaneous melanomas and prostatic adenocarcinomas. Conclusion Our analysis identified ALK positive cases were predominant in adenocarcinoma of lung with EML4-ALK being the most common ALK positive mutation, which is also consistent with the literature. However, the ALK positive mutations were at a lower prevalence rate than that described in the literature. We attribute the lower prevalence rate to underrepresentation of the Asian population in the TCGA database. In addition, we identified extremely rare ALK positive cases in salivary duct carcinomas, melanomas and prostate cancers, thus highlighting the need for testing for these mutations in these cancers.
Sarcoma are rare in head and neck region and radiation induced sarcoma (RIS) are even rare and poses challenges for diagnosis and proper management. We report a case of 38 year old male who was treated for carcinoma of right lateral border of tongue with surgery and radiotherapy, and presented with rapidly progressing mass in right floor of mouth after 4 years. Biopsy and imaging confirmed the diagnosis of radiation induced sarcoma and was managed with wide local excision of mass with hemimandibulectomy with reconstruction by pectoralis major mayocutaneous flap. Patient completed the follow up of one and half year and doing well. RIS of head and neck is rare entity and demands multidisciplinary involvement of head and neck, neuro, reconstructive surgeons, radiation oncologists and medical oncologists for optimal management. Though it has poor prognosis but properly managed patients will have the good quality of life.
Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer and lacks effective targeted therapies. HPV(-) patients have a 50-60% recurrence rate and could benefit from adjuvant therapy. Although HPV(+) patients have a significantly better survival, 20% have persistent/recurrent disease. Therefore, biomarkers could potentially help identify patients that would benefit from adjuvant targeted agents. Our objective was to evaluate if the mutational and biomarker analysis of tumor samples from OPSCC patients predict recurrence and/ or persistence in patients undergoing definitive therapy with curative intent. 44 advanced stage OPSCC patients that underwent comprehensive genomic profiling by Caris Life Sciences were included in this retrospective study. Next Generation Sequencing (NGS) on genomic DNA from FFPE tumors was performed using the Illumina Nextseq (592-gene, n=17)/MiSeq (44-gene, n=23) platform. Tumors were analyzed for total mutational load (TML), CNV’s and microsatellite instability status. IHC for tumor protein expression of ERCC1, PD-L1, RRM1, TrkA/B/C, TS and TUBB3 was performed using automated platforms. The ASCO/CAP scoring criteria and the cutoff points from published evidence was used in IHC evaluation. Of the 44 patients, 27 were HPV(+) tumors and 11 had HPV(-) disease. Patients with lack of progression free survival data were excluded. Only 4 patients in the entire cohort harbored a pathogenic PIK3CA mutation. Among HPV(+) patients, 22 patients were TP53 WT and 2 patients were found to be TP53 mutant. Although there was no significant change in the TML in smokers compared to nonsmokers (mean 8.77 vs 6.5, respectively; p=0.253), TML was higher in HPV(-) smokers compared to HPV(+) nonsmokers (mean 10.33 vs 6.5, p=0.0661). Our study presented a higher incidence of recurrent/persistent disease in the Caucasians (60%) in comparison to African-Americans (21%). Considering the sample size in the current study, the racial difference in outcomes appears likely to be present regardless of HPV status or disease state. The co-occurrence of multiple deleterious mutations was observed in 70% of the non-responders. Particularly, mutations in CHEK2, PTCH, MUTYH were noted in 50% of the recurrent/persistent patients. CNV mutations in SMAD2, MALT1, NFKBIA in 50% of the recurrent/persistent patients were found. The co-occurrence of multiple mutations were absent in responders in spite of an appreciable sample size in the responder group (n=12). This study also affirmed an improved prognosis in patients with HPV(+), with higher expression of TUBB3, and with positive expression of PD-1 in the tumors. Co-occurrence of multiple deleterious mutations were associated with patients who did not respond to therapy. Therefore, combination rescue therapies that can target multiple pathways to abrogate the mutational effects can aid/enhance therapeutic benefits in HNSCC patients. Citation Format: Alok R. Khandelwal, Kelsey Poorman, Tara Moore-Medlin, Xiaohui Ma, Abhijit Gundale, Ronald Horswell, San Chu, Michelle Winerip, Cherie-Ann O. Nathan. Co-occurring mutations in recurrent/persistent head and neck squamous cell carcinoma (HNSCC) patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4023.
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