Blog Archive

Αλέξανδρος Γ. Σφακιανάκης

Wednesday, January 12, 2022

Anatomy of the sphenoidal spine and its implications in endoscopic endonasal surgery of the infratemporal fossa

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Abstract

Background

The sphenoidal spine protrudes from the roof of the infratemporal fossa (ITF). This study aims to assess the anatomic relationships among the sphenoidal spine and other structures within the ITF from the perspective of an endoscopic endonasal access (EEA), and to explore the implications of these relationships.

Methods

An EEA to the ITF was completed on six cadaveric specimens (12 sides). The anatomical relationships among the sphenoidal spine and adjacent structures were explored and associated distances from each other were measured using a navigation system.

Results

The foramen spinosum is located anterosuperior to the sphenoidal spine, whereas the chorda tympani courses caudal and medial to the sphenoidal spine and the Eustachian tube and parapharyngeal internal carotid artery (pICA) are at its posterior aspect. Two virtual vertical planes, at the anterior and posterior aspects of the sphenoidal spine, respectively, correspond to the posterior trunk of V3 and middle meningeal artery, and the stylopharyngeal aponeurosis. The average length of sphenoidal spine was 8.5 ± 2.43 mm, and the distance from distal apex of the sphenoidal spine to the foramen ovale, foramen spinosum, and pICA were 10.82 ± 0.83 mm, 6.42 ± 0.52 mm, and 5.02 ± 0.54 mm, respectively.

Conclusions

The sphenoidal spine is a meaningful landmark for endonasal approaches to the ITF. Measurements and conceptualization of vertical planes prior and posterior to the sphenoidal spine are beneficial to better appreciate the anatomic relationships in the ITF.

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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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Clinicopathological features and outcome of thyroglobulin elevation and negative iodine scintigraphy (TENIS) patients with negative neck ultrasound: Experience from a thyroid carcinoma clinic in India

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World J Nucl Med. 2021 Nov 1;20(4):361-368. doi: 10.4103/wjnm.wjnm_143_20. eCollection 2021 Oct-Dec.

ABSTRACT

Management of differentiated thyroid carcinoma (DTC) patients with thyroglobulin (Tg) elevation and negative iodine scintigraphy (TENIS) and negative neck ultrasound scan causes considerable diagnostic and therapeutic dilemma, especially in resource-poor settings. The aim of this study was to evaluate clinicopathological features and outcome of TENIS patients with negative n eck US attending a thyroid cancer clinic in India. From a DTC database of 722 containing 193 TENIS patients, subjects with negative neck US and negative Tg antibody (TgAb) were selected retrospectively and analyzed using appropriate statistical methods. The study group included 64 patients (male - 17, female - 47, mean age - 44.7 ± 12.8 years) with 54 papillary and 10 follicular thyroid carcinomas, American Thyroid Association (ATA) recurrence risk categorization (2009) - low - 16, intermediate - 28, and high - 2 0. Most of the patients became TENIS within 1 year of diagnosis with median Tg level of 6.5 ng/mL (1.2-996 ng/mL) and mean follow-up of 7.8 years. On follow-up, Tg dropped spontaneously in 27 patients, more among the low and intermediate-risk categories. For those with high or increasing Tg level, further imaging (fluorodeoxyglucose positron emission tomography/computed tomography) was done and 14 out of 18 were positive. Treatment included empiric radioactive iodine thera py-16, external beam radiation therapy (EBRT)-7, and lymph node dissection (LND)-10. A favorable outcome was seen in 36 patients and unfavorable in 28. Distant metastases were associated with unfavorable outcome and poor survival. Progression-free survival was significantly better in the Tg group of <10 at the time of TENIS (111 months) compared to the Tg group >10 (72 months). Tg level dropped spontaneously in nearly half the patients, especially if levels were <10 and more so among the low-risk category. Distant metastasis was predictive of unfavorable outcomes. Along with Tg level, the ATA risk category might help to predict clinical course and reduce unnecessary expensive imaging in resource-poor settings.

PMID:35018 151 | PMC:PMC8686749 | DOI:10.4103/wjnm.wjnm_143_20

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Cerebrospinal fluid external leak after penetrating trauma in a neurologic intact infant patient: a case report

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Childs Nerv Syst. 2022 Jan 12. doi: 10.1007/s00381-021-05440-0. Online ahead of print.

ABSTRACT

Cranial cerebrospinal fluid (CSF) leak is an extremely rare complication of blunt head trauma causing skull fractures, especially fractures involving the skull base. We present the case of a 10-month-old male who received glass fragments on the midline and posterior tier of his anterior fontanelle producing a cranial cerebrospinal fluid leak without any skull fracture or symptoms. Neurologic exam was completely normal and a superficial stitch wound repair was performed. He was observed for 24 h, had no antibiotic, and left with a 1-week outpatient neurosurgical follow-up. The patient had no negative outcome. Cerebrospinal fluid leak should be included in the differential diagnosis of a head trauma in a patient with open fontanelles. No similar case was found in literature.

PMID:35019999 | DOI:10.1007/s00381-021-05440-0

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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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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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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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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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A Notch inhibitor plus Resveratrol induced blockade of autophagy drives glioblastoma cell death by promoting a switch to apoptosis

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Am J Cancer Res. 2021 Dec 15;11(12):5933-5950. eCollection 2021.

ABSTRACT

Glioblastoma multiforme (GBM) is the most common and aggressive form of brain tumors and the hardest type of cancer to treat. Therapies targeting developmental pathways, such as Notch, eliminate neoplastic glioma cells, but their efficacy can be limited by various mechanisms. Combination regimens may represent a good opportunity for effective therapies with durable effects. We used low doses of the γ-secretase inhibitor RO4929097 (GSI), to block the Notch pathway activity, in combination with Resveratrol (RSV) and we evidenced the mechanisms of autophagy/apoptosis transition in GBM cells. Resveratrol and GSI combination results in the synergistic induction of cell death together with the block of the autophagic flux evidenced by a sustained increase of LC3-II and p62 protein content, due to the dramatic reduction of CDK4, an important regulator of lysosomal func tion. The ectopic overexpression of the constitutive active CDK4 mutant, greatly counteracted the RSV+GSI induced block of the autophagy. Triggering autophagy in RSV+GSI-treated cells, which have impaired lysosomal function, caused the collapse of the system and a following apoptosis. For instance, by combining the CDK4 mutant as well as the early stage autophagy inhibitor, 3-methyladenina, abolished the RSV+GSI induced caspases activation. The initiator caspases (caspases-8 and -9), effector caspase (caspase-3) and its downstream substrate PARP were induced after RSV+GSI exposure as well as the percentage of the TUNEL positive cells. Moreover, the pro-apoptotic signaling MAPK p38 was activated while the pro-survival MAPK p42/p44 signaling was inhibited. In short, we establish the role of CDK4 in the regulation of autophagy/apoptosis transition induced by RSV and GSI in GBM cells. This new synergistic therapeutic combination, increasing the accumulation of autophagosomes, may have t herapeutic value for GBM patients.

PMID:35018234 | PMC:PMC8727809

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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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