Wednesday, January 12, 2022

Low Pressure Low Frequency Jet Ventilation: Techniques, Safety and Complications

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Ann Otol Rhinol Laryngol. 2022 Jan 11:34894211072630. doi: 10.1177/00034894211072630. Online ahead of print.

ABSTRACT

OBJECTIVE: Manual jet ventilation is a specialized oxygenation and ventilation technique that is not available in all facilities due to lack of technical familiarity and fear of complications. The objective is to review our center's 15 year experience with low pressure low frequency jet ventilation (LPLFJV).

METHODS: Retrospective review of procedures u tilizing LPLFJV from 2005 to 2019 were performed collecting patient demographic, surgery type and complications. Fisher exact test, Chi square, and t-test were used to determine statistical significance.

RESULTS: Four hundred fifty-seven patients underwent a total of 891 microlaryngeal surgeries-279 cases for voice disorders, 179 for lesions, and 433 for airway stenosis. The peak jet pressure for all cases did not exceed 20 psi and average peak pressure for the last 100 procedures in this case series was 14.9 ± 4.6 psi. The average lowest oxygen saturation for all cases was 95% ± 0.6%. Brief intubation was required in 154 cases (17%). Surgical duration was significantly longer for cases requiring intubation P < .001. The need for intubation was not associated with smoking or cardiopulmonary disease, but was strongly associated with body mass index (BMI). Intubation rates were 7% for normal weight (BMI < 25, N = 216), 13% for overweight (BMI 25-30, N = 282 ), 24% for obese (BMI 30-40, N = 342), and 37% for morbidly obese (BMI > 40, N = 52) patients. Three patients developed respiratory distress in the recovery unit and 2 patients required intubation.

CONCLUSION: LPLFJV assisted by intermittent endotracheal intubation is an exceedingly safe and effective intraoperative oxygenation and ventilationmodality for a broad variety of laryngeal procedure.

PMID:35016557 | DOI:10.1177/00034894211072630

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Surgical Risk Prediction for Nasolacrimal Duct Obstruction in Radioactive Iodine-Treated Thyroid Cancer: A Nationwide Cohort Study

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Thyroid, Ahead of Print.
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Cochlear implant in vestibular schwannomas: long-term outcomes and critical analysis of indications

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Eur Arch Otorhinolaryngol. 2022 Jan 12. doi: 10.1007/s00405-021-07243-0. Online ahead of print.

ABSTRACT

PURPOSE: To describe our institutional experience in cochlear implantation after vestibular schwannoma (VS) resection, and compare the audiological outcomes between sporadic and neurofibromatosis type 2 (NF2) VS sub-cohorts of patients, and in relation to preoperative contralateral hearing.

METHODS: Seventeen patients (8 sporadic and 9 NF2-associated VSs) who had undergone VS resection and cochlear implant (CI) were analyzed retrospectively. Audiological outcomes at 24 months were correlated with preoperative clinical variables. The results according to VS type (sporadic vs. NF2-associated) and contralateral hearing (impaired vs. normal) were compared.

RESULTS: Fourteen CIs were actively used by the patients (77.8%). Twenty-four months after CI activation, the median postoperative PTA (pure tone average) was 45.6 dB nHL and a measurable WRS (Word Recognition Score) was achieved by 44.4% of patients (median WRS = 40%). The median postoperative PTA in the implanted ear resulted better in the group with an impaired contralateral hearing (36.3 dB nHL vs. 78.8 dB nHL, p = 0.019). Good preoperative contralateral hearing status (A-B classes of AAO-HNS) was a negative prognostic factor for CI performance on open-set discrimination (OR = 28.0, 95% CI 2.07-379.25, p = 0.012).

CONCLUSIONS: CI is a viable rehabilitative option for patients with sporadic or NF2-associated VS. A good contralateral hearing adversely affects CI outcome and should be taken into consideration for patients' selection and rehabilitation programs.

PMID:35018505 | DOI:10.1007/s00405-021-07243-0

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A prediction model for recurrence after translabyrinthine surgery for vestibular schwannoma: toward personalized postoperative surveillance

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Eur Arch Otorhinolaryngol. 2022 Jan 12. doi: 10.1007/s00405-021-07244-z. Online ahead of print.

ABSTRACT

PURPOSE: The aim of this study is to compute and validate a statistical predictive model for the risk of recurrence, defined as regrowth of tumor necessitating salvage treatment, after translabyrinthine removal of vestibular schwannomas to individualize postoperative surveillance.

METHODS: The multivariable predictive model for risk of recurrence was based on retrospectively collected patient data between 1995 and 2017 at a tertiary referral center. To assess for internal validity of the prediction model tenfold cross-validation was performed. A 'low' calculated risk of recurrence in this study was set at < 1%, based on clinical criteria and expert opinion.

RESULTS: A total of 596 patients with 33 recurrences (5.5%) were included for analysis. The final prediction model consisted of the predictors 'age at time of surg ery', 'preoperative tumor growth' and 'first postoperative MRI outcome'. The area under the receiver operating curve of the prediction model was 89%, with a C-index of 0.686 (95% CI 0.614-0.796) after cross-validation. The predicted probability for risk of recurrence was low (< 1%) in 373 patients (63%). The earliest recurrence in these low-risk patients was detected at 46 months after surgery.

CONCLUSION: This study presents a well-performing prediction model for the risk of recurrence after translabyrinthine surgery for vestibular schwannoma. The prediction model can be used to tailor the postoperative surveillance to the estimated risk of recurrence of individual patients. It seems that especially in patients with an estimated low risk of recurrence, the interval between the first and second postoperative MRI can be safely prolonged.

PMID:35020036 | DOI:10.1007/s00405-021-07244-z

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Cancer stem cells: a major culprit of intra-tumor heterogeneity

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Am J Cancer Res. 2021 Dec 15;11(12):5782-5811. eCollection 2021.

ABSTRACT

Cancer is recognized as a preeminent factor of the world's mortality. Although various modalities have been designed to cure this life-threatening ailment, a significant impediment in the effective output of cancer treatment is heterogeneity. Cancer is characterized as a heterogeneous health disorder that comprises a distinct group of transformed cells to assist anomalous proliferation of affected cells. Cancer stem cells (CSCs) are a leading cause of cancer heterogeneity that is continually transformed by cellular extrinsic and intrinsic factors. They intensify neoplastic cells aggressiveness by strengthening their dissemination, relapse and therapy resistance. Considering this viewpoint, in this review article we have discussed some intrinsic (transcription factors, cell signaling pathways, genetic alterations, epigenetic modifications, non-coding RNAs (ncRNAs) and epitranscriptomics) and extrinsic factors (tumor microenvironment (TME)) that contribute to CSC heterogeneity and plasticity, which may help scientists to meddle these processes and eventually improve cancer research and management. Besides, the potential role of CSCs heterogeneity in establishing metastasis and therapy resistance has been articulated which signifies the importance of developing novel anticancer therapies to target CSCs along with targeting bulk tumor mass to achieve an effective output.

PMID:35018226 | PMC:PMC8727794

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The biochemical and clinical implications of phosphatase and tensin homolog deleted on chromosome ten in different cancers

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Am J Cancer Res. 2021 Dec 15;11(12):5833-5855. eCollection 2021.

ABSTRACT

Phosphatase and tensin homolog deleted on chromosome ten (PTEN) is widely known as a tumor suppressor gene. It is located on chromosome 10q23 with 200 kb, and has dual activity of both protein and lipid phosphatase. In addition, as a targeted gene in multiple pathways, PTEN has a variety of physiological activities, such as those regulating the cell cycle, inducing cell apoptosis, and inhibiting cell invasion, etc. The PTEN gene have been identified in many kinds of cancers due to its mutations, deletions and inactivation, such as lung cancer, liver cancer, and breast cancer, and they are closely connected with the genesis and progression of cancers. To a large extent, the tumor suppressive function of PTEN is realized through its inhibition of the PI3K/AKT signaling pathway which controls cells apoptosis and development. In addition, PTEN loss has been associate d with the prognosis of many cancers, such as lung cancer, liver cancer, and breast cancer. PTEN gene is related to many cancers and their pathological development. On the basis of a large number of related studies, this study describes in detail the structure, regulation, function and classical signal pathways of PTEN, as well as the relationship between various tumors related to PTEN. In addition, some drug studies targeting PTEN/PI3K/AKT/mTOR are also introduced in order to provide some directions for experimental research and clinical treatment of tumors.

PMID:35018228 | PMC:PMC8727805

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PI3-kinase inhibition as a strategy to suppress the leukemic stem cell niche in Ph+ chronic myeloid leukemia

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Am J Cancer Res. 2021 Dec 15;11(12):6042-6059. eCollection 2021.

ABSTRACT

Recent data suggest that the disease-associated microenvironment, known as the leukemic stem cell (LSC) niche, is substantially involved in drug resistance of LSC in BCR-ABL1+ chronic myeloid leukemia (CML). Attacking the LSC niche in CML may thus be an effective approach to overcome drug resistance. We have recently shown that osteoblasts are a major site of niche-mediated LSC resistance against second- and third-generation tyrosine kinase inhibitors (TKI) in CML. In the present study, we screened for drugs that are capable of suppressing the growth and viability of osteoblasts and/or other niche cells and can thereby overcome TKI resistance of CML LSC. Proliferation was analyzed by determining 3H-thymidine uptake in niche-related cells, and apoptosis was measured by Annexin-V/DAPI-staining and flow cytometry. We found that the dual PI3 kin ase (PI3K) and mTOR inhibitor BEZ235 and the selective pan-PI3K inhibitor copanlisib suppress proliferation of primary osteoblasts (BEZ235 IC50: 0.05 μM; copanlisib IC50: 0.05 μM), the osteoblast cell line CAL-72 (BEZ235 IC50: 0.5 μM; copanlisib IC50: 1 μM), primary umbilical vein-derived endothelial cells (BEZ235 IC50: 0.5 μM; copanlisib IC50: 0.5 μM), and the vascular endothelial cell line HMEC-1 (BEZ235 IC50: 1 μM; copanlisib IC50: 1 μM), whereas no comparable effects were seen with the mTOR inhibitor rapamycin. Furthermore, we show that BEZ235 and copanlisib cooperate with nilotinib and ponatinib in suppressing proliferation and survival of osteoblasts and endothelial cells. Finally, BEZ235 and copanlisib were found to overcome osteoblast-mediated resistance against nilotinib and ponatinib in K562 cells, KU812 cells and primary CD34+/CD38- CML LSC. Together, targ eting osteoblastic niche cells through PI3K inhibition may be a new effective approach to overcome niche-induced TKI resistance in CML. Whether this approach can be translated into clinical application and can counteract drug resistance of LSC in patients with CML remains to be determined in clinical trials.

PMID:35018241 | PMC:PMC8727792

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Assessment of age, period, and cohort effects of lung cancer incidence in Hong Kong and projection up to 2030 based on changing demographics

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Am J Cancer Res. 2021 Dec 15;11(12):5902-5916. eCollection 2021.

ABSTRACT

The burden of lung cancer in Hong Kong continues to rise. We analyzed trends in lung cancer incidence and associations with age, period, and cohort from 1985 to 2019, made projections up to 2030 and examined the drivers of lung cancer incidence. We used age-period-cohort modeling to estimate age, period, and cohort effects on lung cancer incidence rates in Hong Kong between 1985 and 2019. We projected lung cancer incidence in Hong Kong from 2020 to 2030 using Bayesian age-period-cohort analysis with an integrated nested Laplace approximation. We decomposed changes in the number of lung cancer cases into population growth, population aging, and epidemiologic changes. From 1985 to 2019, the number of lung cancer incident cases in Hong Kong continued to rise, yet the age-standardized incidence rates have declined for both sexes while have fluctuated for females over the past two decades. The overall annual percentage change from 1985 to 2019 was -2.29 (95% CI, -2.53 to -2.05) for males and -0.86 (95% CI, -1.06 to -0.65) for females. Age-specific annual percentages for both sexes showed a decreasing trend in all age groups and were more pronounced for females older than 65 years and males younger than 65 years. Period effects for both sexes showed a similar monotonic downward pattern, with the downward trend slowing for females after 2000. The cohort effect declined monotonically for males and started to plateau for females after the 1945 birth cohort. It was projected that the incident cases of lung cancer in Hong Kong would continue to increase, with 4,435 male cases and 3,561 female cases in 2030. Demographic decomposition suggested that population growth and population aging play an important role in the change of lung cancer cases. Much progress has been made in reducing the incidence of lung cancer in Hong Kong, but this has been offset b y demographic changes that will continue to increase the incident cases of lung cancer in Hong Kong, especially among females. There is an urgent need for continued public health policies and clinical programs for risk factor control and necessary screening.

PMID:35018232 | PMC:PMC8727798

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MicroRNA-187 exerts tumor-suppressing functions in osteosarcoma by targeting ZEB2 [Retraction]

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Am J Cancer Res. 2021 Dec 15;11(12):6218. eCollection 2021.

ABSTRACT

[This retracts the article on p. 2859 in vol. 6, PMID: 28042505.].

PMID:35018254 | PMC:PMC8727813

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Chemotherapy-induced cytokines and prognostic gene signatures vary across breast and colorectal cancer

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Am J Cancer Res. 2021 Dec 15;11(12):6086-6106. eCollection 2021.

ABSTRACT

The mechanisms by which chemotherapeutic drugs mediate efficacy and toxicity in patients across cancers are not fully understood. A poorly understood aspect of the tumor cell response to chemotherapy is cytokine regulation. Some drug-induced cytokines promote the anti-cancer activity of the drugs, but others may promote proliferation, metastasis, and drug resistance. We evaluated effects of clinical chemotherapeutics oxaliplatin, cisplatin, 5-fluorouracil (5-FU), doxorubicin, paclitaxel, docetaxel, and carboplatin on a panel of 52 cytokines in MCF7 breast cancer (BC) cells. We observed pan-drug effects, such as the upregulation of TRAIL-R2 and Chitinase 3-like 1 and drug-specific effects on interleukin and CXCL cytokines. We compared cytokine regulation in MCF7 BC and HCT116 colorectal cancer (CRC) cells, revealing tissue-specific drug effects such as enhanced up regulation of TRAIL-R2 and downregulation of IFN-β and TRAIL in MCF7 by cisplatin, oxaliplatin, and 5-FU. We found that chemotherapy-inducible transcripts have varying potential for prognostic significance in CRC versus BC. Among the non-prognostic CRC genes that were prognostic in BC were NFKBIA and GADD45A, both of which support anti-cancer drug mechanisms. Thus, we establish a novel 7-drug, 52-cytokine signature in MCF7 BC cells and a 3-drug, 40-cytokine signature in HCT116 CRC cells that suggest drug-specific and tissue-specific cytokine regulation. Distinct differences across prognostic gene signatures in BC and CRC further support tissue specificity in the relative impact of drug-regulated genes on patient survival.

PMID:35 018244 | PMC:PMC8727797

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Paracrine production of IL-6 promotes a hypercoagulable state in pancreatic cancer

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Am J Cancer Res. 2021 Dec 15;11(12):5992-6003. eCollection 2021.

ABSTRACT

Venous thromboembolism is the most common complication and the secondary cause of death in pancreatic cancer. Moreover, the hypercoagulable state induces microcirculation dysfunction, acidosis and hypoxia, and further enhances tumor immune evasion, tumor growth and metastasis. Numerous studies have revealed that patients with malignant tumors have high levels of IL-6, which stimulates hepatocytes to synthesize thrombopoietin, causing an increase in platelets. This study found that the concentration of IL-6 in pancreatic cancer patient sera was higher than that in healthy donors, while pancreatic cancer cells had low expression levels of IL-6, which was different from other types of cancer. This contradictory result prompted us to uncover the underlying mechanism. Our data revealed that pancreatic cancer enhanced IL-6 production in fibroblasts via the Jagged/Notch axis, while IL-6 further elevated Jagged-1/2 expression in a paracrine positive feedback loop in pancreatic cancer. Inhibition experiments and RNAi studies demonstrated that IL-6-induced Jagged-1/2 production in pancreatic cancer depended on STAT3 and that Jagged-1/2 enhanced IL-6 mRNA expression in HSFs through the NF-κB pathway. Finally, the animal study showed that knockdown of Jagged-1/2 or blockade of the Jagged/Notch pathway by Nirogacestat could alleviate pancreatic cancer-induced hypercoagulability. Accordingly, our findings clarified the key role of the Jagged/Notch/IL-6/STAT3 feedback loop in the development of a hypercoagulable state in pancreatic cancer, which also provides new therapeutic strategies for pancreatic cancer patients who suffer from hypercoagulability.

PMID:35018238 | PMC:PMC8727799

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