12 results on '"Kakarala K"'
Search Results
2. 1978TiP - A window of opportunity trial of atorvastatin targeting p53 mutant malignancies
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Baranda, J.C., Bur, A., Tsue, T., Shnayder, L., Kakarala, K., Telfah, M., Lin, T., Williamson, S.K., Al-Kasspooles, M., Ashcraft, J., Lakis, N., Madan, R., Khan, Q., Saeed, A., Reed, G., Weir, S., Godwin, A., Thomas, S., Komiya, T., and Iwakuma, T.
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- 2019
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3. Six-week postoperative opioid use and pain following a randomized controlled trial evaluating multimodal analgesia for head and neck free flap patients.
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Wagoner SF, Lawrence AS, Alapati R, Renslo B, Hamill CS, Bon Nieves A, Baumanis M, Bur AM, Kakarala K, Sykes KJ, and Shnayder Y
- Abstract
Introduction: Head and neck malignancy treatment often involves invasive surgeries, necessitating effective postoperative pain control. However, chronic reliance on opioid medications remains a challenge for many patients after surgery. Multimodal analgesia (MMA) within enhanced recovery after surgery protocols has shown success in limiting narcotic pain medications for other cancer types. In a prior study, MMA comprising acetaminophen, ketorolac, gabapentin, and a neurogenic block reduced opioid use in the 7-day postoperative period for major head and neck reconstructive surgery. This study investigates the impact of multimodal analgesia on opioid prescription and pain during the 6-week postoperative period for patients undergoing major head and neck oncologic surgeries, aiming to understand the longer-term effects of narcotic use., Methods: The study retrospectively examined participants in a [hybrid type 1 effectiveness-implementation pragmatic trial to assess multimodal analgesia's long-term effectiveness in head and neck free flap surgery. Arm A received scheduled acetaminophen and as-needed opioids, while Arm B received scheduled gabapentin, ketorolac, a regional nerve block at the donor site, scheduled acetaminophen, and as-needed opioids. Retrospective data collection included opioid prescription use and pain scores up to 6 weeks after surgery, gathered from the Kansas prescription drug monitoring program, K-TRACS., Results: Thirty patients participated, 14 in Arm A and 16 in Arm B. The average morphine milligram equivalents per day of filled prescriptions were not significantly different between Arm A and Arm B (7.23 vs. 7.88, p = .845). Additionally, average pain scores at 6 weeks showed no significant difference between the two groups (1.4 vs. 1.9, p = .612)., Conclusion: Patients with head and neck cancer treated with multimodal analgesia during the perioperative period did not exhibit significant differences in opioid use and pain within 6 weeks after discharge. To confirm these findings, a re-examination with strict measures of opioid use and scheduled pain assessments in a prospective manner is warranted., Level of Evidence: 4., Competing Interests: The authors declare no conflicts of interest., (© 2024 The Authors. Laryngoscope Investigative Otolaryngology published by Wiley Periodicals LLC on behalf of The Triological Society.)
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- 2024
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4. Disentangling Social Determinants of Health and Rurality in Head and Neck Cancer 2-Year Mortality.
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Virgen C, Renslo B, Sawaf T, Shnayder Y, Kakarala K, Bur AM, and Sykes KJ
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Social determinants of health (SDoH) and rurality are known factors that may influence outcomes in head and neck squamous cell carcinoma (HNSCC). Patients residing in remote locations or those with multiple SDoH may encounter barriers to initial diagnosis, adherence to multidisciplinary treatments, and posttreatment surveillance, which may impact their overall survival. However, previous studies have shown mixed results associated with rural residence. The aim of this study is to identify the impact of rurality and SDoH on 2-year survival in HNSCC. The study was conducted using a Head and Neck Cancer Registry at a single institution from June 2018 through July 2022. Rurality, defined by US census scores, and individual measures of SDoH were used. Our results indicate that each additional adverse SDoH factor results in 1.5 times the odds of mortality at 2 years. Individualized measures of SDoH, rather than rurality alone, better reflect patient prognosis in HNSCC., Competing Interests: None., (© 2023 The Authors. OTO Open published by Wiley Periodicals LLC on behalf of American Academy of Otolaryngology–Head and Neck Surgery Foundation.)
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- 2023
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5. Sarcopenia and Treatment Toxicity in Older Adults Undergoing Chemoradiation for Head and Neck Cancer: Identifying Factors to Predict Frailty.
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Morse RT, Ganju RG, Gan GN, Cao Y, Neupane P, Kakarala K, Shnayder Y, and Lominska CE
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This study was performed to identify treatment related toxicities in older adults undergoing concurrent chemoradiotherapy for head and neck cancer and nutritional and skeletal muscle measures that might identify frailty. Imaging analysis was done with the following skeletal muscle measurements: skeletal muscle index (SMI), skeletal muscle density (SMD), and skeletal muscle gauge (SMG). Patients were dichotomized by age into younger (<70 years old, 221 patients) and older age groups (≥70 years old, 51 patients). Low SMI was more common in older patients (86.7%) compared to younger patients (51.7%, p < 0.01), as were low SMD (57.8% vs. 37.3%, p = 0.012) and low SMG (76.1% vs. 44.2%, p < 0.01), despite having similar BMIs (27.3 kg/m2 versus 27.7 kg/m2, p = 0.71). Older patients were significantly more likely to experience chemotherapy toxicity than younger patients (54.9% versus 32.3%, p < 0.01). On multivariate analysis age (p < 0.01), current smoking status (p < 0.01), and low SMI (p < 0.01) remained as significant predictors for missed chemotherapy cycles or discontinuation. Older patients were more likely to require ≥5-day radiation breaks than younger patients (27.5% versus 8.6%, p < 0.01). On multivariate analysis, age (p < 0.01), low albumin status (p = 0.03), and low SMI (p = 0.04) were identified as predictors of prolonged radiation treatment breaks. Based on the results of our study, sarcopenia may be used as an additional marker for frailty alongside traditional performance status scales.
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- 2022
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6. Recognizing a MIS-Chievous Cause of Acute Viral Gastroenteritis.
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Josyabhatla R, Kamdar AA, Armbrister SA, Daniel R, Boukas K, Smith KG, Van Arsdall MR, Kakarala K, Flores AR, Wanger A, Liu Y, and Rhoads JM
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Historically, children evaluated for vomiting and diarrhea secondary to viral enteritis have symptoms lasting 2-4 days and respond to supportive care, including oral rehydration and anti-emetics if required. Recently, within a 14-day timespan, we encountered three children with severe diarrhea who rapidly became dehydrated and went into hypotensive shock. Although SARS-CoV-2 molecular tests were negative by nasopharyngeal swab, all were later found to have MIS-C. This small case series underscores features reported in previous larger studies and emphasizes the rapid clinical evolution of this condition. We highlight the importance of early recognition of cardinal laboratory findings characteristic of MIS-C (i.e., lymphopenia, markedly elevated acute phase reactants, and hypoalbuminemia). We also show serologic evidence that the pathophysiological mechanism of SARS-CoV-2 related diarrhea may differ from other causes of dehydrating vomiting and diarrhea, with no serologic evidence of villus cell injury., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Josyabhatla, Kamdar, Armbrister, Daniel, Boukas, Smith, Van Arsdall, Kakarala, Flores, Wanger, Liu and Rhoads.)
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- 2021
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7. Rhabdomyolysis in a Morbidly Obese Patient After Oral Cavity Free Flap Reconstruction.
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Wichova H, Subbarayan R, Muelleman T, and Kakarala K
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Post-operative rhabdomyolysis is a rare but life-threatening condition. Less than ten cases have been described in the otolaryngic literature and, to our knowledge, no reports exist in the setting of oral reconstructive free tissue transfer. Case report presentation. We discuss the clinical course that lead to the diagnosis of rhabdomyolysis with special consideration to simultaneous microvascular anastomosis. Serial lab values were closely followed to prevent kidney injury while preventing flap congestion. Excessive fluid resuscitation in free flap reconstruction has been associated with increased post-operative complications and flap failure. We present a cautionary case to highlight the need for early diagnosis of rhabdomyolysis, a condition that may become more prevalent in the head and neck population as obesity, the main risk factor, continues to increase worldwide., Competing Interests: Conflict of interestAll authors declare that they have no conflict of interest., (© Association of Otolaryngologists of India 2018.)
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- 2019
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8. Potent Antitumor Effects of a Combination of Three Nutraceutical Compounds.
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Vishwakarma V, New J, Kumar D, Snyder V, Arnold L, Nissen E, Hu Q, Cheng N, Miller D, Thomas AR, Shnayder Y, Kakarala K, Tsue TT, Girod DA, and Thomas SM
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- Animals, Antineoplastic Agents metabolism, Apoptosis drug effects, Arum, Benzaldehydes pharmacology, Carcinoma, Squamous Cell pathology, Cell Line, Tumor, Cell Proliferation drug effects, Cisplatin pharmacology, Combined Modality Therapy, Curcuma, Curcumin pharmacology, Dietary Supplements, ErbB Receptors metabolism, Harmine pharmacology, Head and Neck Neoplasms drug therapy, Humans, Mice, Mice, Nude, Molecular Docking Simulation, Peganum, Signal Transduction drug effects, Xenograft Model Antitumor Assays, Antineoplastic Combined Chemotherapy Protocols pharmacology, Plant Extracts pharmacology, Squamous Cell Carcinoma of Head and Neck drug therapy
- Abstract
Head and neck squamous cell carcinoma (HNSCC) is associated with low survival, and the current aggressive therapies result in high morbidity. Nutraceuticals are dietary compounds with few side effects. However, limited antitumor efficacy has restricted their application for cancer therapy. Here, we examine combining nutraceuticals, establishing a combination therapy that is more potent than any singular component, and delineate the mechanism of action. Three formulations were tested: GZ17-S (combined plant extracts from Arum palaestinum, Peganum harmala and Curcuma longa); GZ17-05.00 (16 synthetic components of GZ17-S); and GZ17-6.02 (3 synthetic components of GZ17S; curcumin, harmine and isovanillin). We tested the formulations on HNSCC proliferation, migration, invasion, angiogenesis, macrophage viability and infiltration into the tumor and tumor apoptosis. GZ17-6.02, the most effective formulation, significantly reduced in vitro assessments of HNSCC progression. When combined with cisplatin, GZ17-6.02 enhanced anti-proliferative effects. Molecular signaling cascades inhibited by GZ17-6.02 include EGFR, ERK1/2, and AKT, and molecular docking analyses demonstrate GZ17-6.02 components bind at distinct binding sites. GZ17-6.02 significantly inhibited growth of HNSCC cell line, patient-derived xenografts, and murine syngeneic tumors in vivo (P < 0.001). We demonstrate GZ17-6.02 as a highly effective plant extract combination and pave the way for future clinical application in HNSCC.
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- 2018
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9. Cancer-Associated Fibroblasts Drive Glycolysis in a Targetable Signaling Loop Implicated in Head and Neck Squamous Cell Carcinoma Progression.
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Kumar D, New J, Vishwakarma V, Joshi R, Enders J, Lin F, Dasari S, Gutierrez WR, Leef G, Ponnurangam S, Chavan H, Ganaden L, Thornton MM, Dai H, Tawfik O, Straub J, Shnayder Y, Kakarala K, Tsue TT, Girod DA, Van Houten B, Anant S, Krishnamurthy P, and Thomas SM
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- Animals, Cancer-Associated Fibroblasts metabolism, Cell Line, Tumor, Cell Movement physiology, Disease Progression, Head and Neck Neoplasms metabolism, Humans, Mice, Mice, Nude, Oxidative Phosphorylation, Proto-Oncogene Proteins c-met metabolism, Receptor Protein-Tyrosine Kinases metabolism, Signal Transduction physiology, Squamous Cell Carcinoma of Head and Neck metabolism, Up-Regulation physiology, Cancer-Associated Fibroblasts pathology, Glycolysis physiology, Head and Neck Neoplasms pathology, Squamous Cell Carcinoma of Head and Neck pathology
- Abstract
Despite aggressive therapies, head and neck squamous cell carcinoma (HNSCC) is associated with a less than 50% 5-year survival rate. Late-stage HNSCC frequently consists of up to 80% cancer-associated fibroblasts (CAF). We previously reported that CAF-secreted HGF facilitates HNSCC progression; however, very little is known about the role of CAFs in HNSCC metabolism. Here, we demonstrate that CAF-secreted HGF increases extracellular lactate levels in HNSCC via upregulation of glycolysis. CAF-secreted HGF induced basic FGF (bFGF) secretion from HNSCC. CAFs were more efficient than HNSCC in using lactate as a carbon source. HNSCC-secreted bFGF increased mitochondrial oxidative phosphorylation and HGF secretion from CAFs. Combined inhibition of c-Met and FGFR significantly inhibited CAF-induced HNSCC growth in vitro and in vivo ( P < 0.001). Our cumulative findings underscore reciprocal signaling between CAF and HNSCC involving bFGF and HGF. This contributes to metabolic symbiosis and a targetable therapeutic axis involving c-Met and FGFR. Significance: HNSCC cancer cells and CAFs have a metabolic relationship where CAFs secrete HGF to induce a glycolytic switch in HNSCC cells and HNSCC cells secrete bFGF to promote lactate consumption by CAFs. Cancer Res; 78(14); 3769-82. ©2018 AACR ., (©2018 American Association for Cancer Research.)
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- 2018
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10. Secretory Autophagy in Cancer-Associated Fibroblasts Promotes Head and Neck Cancer Progression and Offers a Novel Therapeutic Target.
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New J, Arnold L, Ananth M, Alvi S, Thornton M, Werner L, Tawfik O, Dai H, Shnayder Y, Kakarala K, Tsue TT, Girod DA, Ding WX, Anant S, and Thomas SM
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- Animals, Cancer-Associated Fibroblasts immunology, Cell Line, Tumor, Cell Movement, Cell Proliferation physiology, Chloroquine pharmacology, Culture Media, Conditioned metabolism, Cytokines metabolism, Drug Resistance, Neoplasm, Female, Humans, Male, Mice, Mice, SCID, Neoplasm Invasiveness pathology, Pyridines pharmacology, Pyrimidinones pharmacology, Squamous Cell Carcinoma of Head and Neck, Xenograft Model Antitumor Assays, Autophagy physiology, Cancer-Associated Fibroblasts pathology, Carcinoma, Squamous Cell pathology, Fibroblast Growth Factor 2 metabolism, Head and Neck Neoplasms pathology, Interleukin-6 metabolism, Interleukin-8 metabolism
- Abstract
Despite therapeutic advancements, there has been little change in the survival of patients with head and neck squamous cell carcinoma (HNSCC). Recent results suggest that cancer-associated fibroblasts (CAF) drive progression of this disease. Here, we report that autophagy is upregulated in HNSCC-associated CAFs, where it is responsible for key pathogenic contributions in this disease. Autophagy is fundamentally involved in cell degradation, but there is emerging evidence that suggests it is also important for cellular secretion. Thus, we hypothesized that autophagy-dependent secretion of tumor-promoting factors by HNSCC-associated CAFs may explain their role in malignant development. In support of this hypothesis, we observed a reduction in CAF-facilitated HNSCC progression after blocking CAF autophagy. Studies of cell growth media conditioned after autophagy blockade revealed levels of secreted IL6, IL8, and other cytokines were modulated by autophagy. Notably, when HNSCC cells were cocultured with normal fibroblasts, they upregulated autophagy through IL6, IL8, and basic fibroblast growth factor. In a mouse xenograft model of HNSCC, pharmacologic inhibition of Vps34, a key mediator of autophagy, enhanced the antitumor efficacy of cisplatin. Our results establish an oncogenic function for secretory autophagy in HNSCC stromal cells that promotes malignant progression. Cancer Res; 77(23); 6679-91. ©2017 AACR ., (©2017 American Association for Cancer Research.)
- Published
- 2017
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11. Gastropericardial fistula as a delayed complication of a Nissen fundoplication.
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Kakarala K, Edriss H, and Nugent K
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A 41-year-old man presented to the emergency department with substernal chest pain and was found to have ST elevations in the inferior leads on his electrocardiogram. An emergent cardiac catheterization did not identify significant coronary narrowing. Computed tomography of the thorax demonstrated a pneumopericardium and a hiatal hernia. The patient had a complicated past surgical history, including a Nissen fundoplication and three additional surgeries for postoperative complications. An esophagram later revealed an ulcer and possible fistula, and the patient underwent gastropericardial fistula resection after the fistula failed to close with fibrin sealant application. Enteropericardial fistulas occur infrequently but have high morbidity and mortality rates. This possibility is much more likely in patients with prior gastroesophageal surgery, including laparoscopic Nissen fundoplication.
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- 2015
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12. Reconstruction of a nasopharyngeal defect from cervical spine osteoradionecrosis.
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Kakarala K, Richmon JD, Durand ML, Borges LF, and Deschler DG
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Osteoradionecrosis of the cervical spine is a rare complication of radiation treatment of head and neck tumors that requires a multidisciplinary approach to management and reconstruction. The case of a 57-year-old man with osteoradionecrosis of the cervical spine secondary to radiation for metastatic hepatocellular carcinoma is presented. Operative debridement of the necrotic bone was performed and the nasopharyngeal soft tissue defect was reconstructed with a radial forearm free flap. The management and reconstruction options for osteoradionecrosis of the cervical spine are discussed.
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- 2010
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