Comparative Analysis on Vestibular Schwannoma Surgery with and without Intraoperative Fluorescein Sodium Enhancement.

BACKGROUND: Vestibular schwannoma (VS), also known as acoustic neuroma, is a benign, well-encapsulated, and slow-growing tumor that originates from Schwann cells, which form the myelin sheath around the vestibulocochlear nerve (VIII cranial nerve). The surgical treatment of this condition presents a challenging task for surgeons, as the tumor's location and size make it difficult to remove without causing damage to the surrounding structures. In recent years, fluorescein sodium (FS) has been proposed as a tool to enhance surgical outcomes in VS surgery. This essay will provide an analytical comparison of the use of FS in VS surgery, evaluating its benefits and limitations and comparing surgical outcomes with and without FS-assisted surgery. METHODS: In a retrospective study conducted at San Filippo Neri Hospital, we examined VS cases that were operated on between January 2017 and December 2023. The patients were divided into two groups: group A, which consisted of patients who underwent surgery without the use of FS until January 2020 (102 cases), and group B, which included patients who underwent surgery with FS after January 2020 (55 cases). All operations were performed using the retrosigmoid approach, and tumor size was classified according to the Koos, et al. classification system. The extent of surgical removal was evaluated using both the intraoperative surgeon's opinion and postoperative MRI imaging. Preoperatively and postoperatively, facial nerve function and hearing were assessed. In group B, FS was used to assist the surgical procedures, which were performed using a surgical microscope equipped with an integrated fluorescein filter. Postoperative clinical and MRI controls were performed at six months and annually, with no patients lost to follow-up. RESULTS: This study investigated the impact of intraoperative fluorescein exposure on tumor resection and clinical outcomes in patients with VS. The study found a statistically significant difference in the tumor resection rates between patients who received fluorescein intraoperatively (p = 0.037). Further analyses using the Koos classification system revealed a significant effect of fluorescein exposure, particularly in the Koos 3 subgroup (p = 0.001). Notably, no significant differences were observed in hearing loss or facial nerve function between the two groups. A Spearman correlation analysis revealed a positive correlation between tumor size and Koos, age, and size, but no significant correlation was found between facial nerve function tests. CONCLUSIONS: FS-assisted surgery for VS may potentially enhance tumor resection, allowing for more comprehensive tumor removal.

Optimization of long-range PCR protocol to prepare filaggrin exon 3 libraries for PacBio long-read sequencing.

BACKGROUND: The filaggrin (FLG) protein, encoded by the FLG gene, is an intermediate filament-associated protein that plays a crucial role in the terminal stages of human epidermal differentiation. Loss-of-function mutations in the FLG exon 3 have been associated with skin diseases. The identification of causative mutations is challenging, due to the high sequence homology within its exon 3 (12,753 bp), which includes 10 to 12 filaggrin tandem repeats. With this study we aimed to obtain the whole FLG exon 3 sequence through PacBio technology, once 13-kb amplicons have been generated. METHODS AND RESULTS: For the preparation of SMRTbell libraries to be sequenced using PacBio technology, we focused on optimizing a 2-step long-range PCR protocol to generate 13-kb amplicons covering the whole FLG exon 3 sequence. The performance of three long-range DNA polymerases was assessed in an attempt to improve the PCR conditions required for the enzymes to function properly. We focused on optimization of the input template DNA concentration and thermocycling parameters to correctly amplify the entire FLG exon 3 sequence, minimizing non-specific amplification. CONCLUSIONS: Taken together, our findings suggested that the PrimeSTAR protocol is suitable for producing the amplicons of the 13-kb FLG whole exon 3 to prepare SMRTbell libraries. We suggest that sequencing the generated amplicons may be useful for identifying LoF variants that are causative of the patients' disorders.

Dietary supplements in lymphedema.

Lymphedema is a chronic inflammatory disorder resulting from ineffective fluid uptake by the lymphatic system, and the effects are principally felt in the lower limbs. The condition is said to be primary when caused by genetic mutations and secondary when caused by injuries, infections, or surgery. Lymphedema, a worldwide pathology, does not have an effective therapy so far. Leukotriene B4 has recently been identified as a key molecule in lymphedema pathogenesis. Surgical, nonsurgical, and pharmacological treatments have been proposed; however, they do not cure the disease and only ameliorate the symptoms. Nutrition and nutritional status are extremely important in lymphedema physiopathology. Obesity is a comorbidity that exacerbates the risk for secondary lymphedema and constitutes a negative prognostic factor. Indeed, anti-inflammatory foods and their effects on the inflammatory state and on oxidative stress are now being investigated for their possible therapeutic role in lymphedema. Although no special diet has so far been proven to be very effective, specific dietary tips could help in alleviating the edematous state of patients with lymphedema. A few supplements have been tested for lymphedema treatment. Among them, GARLIVE® containing hydroxytyrosol, hesperidin, spermidine and vitamin A, exhibited promising effects in the animal model. Hydroxytyrosol, a polyphenol from olives, showed anti-inflammatory effects and reduced leukotriene B4 synthesis, thus holding promise as a potential natural candidate for lymphedema treatment.

Dietary supplements for lipedema.

Lipedema is a chronic disease that mostly manifests in females as the abnormal distribution of subcutaneous adipose connective tissue, usually coupled with bruising, pain, and edema. Lipedema molecular pathophysiology is currently not clear, but several studies suggest that genetics and hormonal imbalance participate in lipedema pathogenesis. Women with lipedema present in some cases with elevated body mass index, and the appearance of obesity in addition to lipedema, where the obesity can cause serious health issues as in lipedema-free individuals with obesity, such as diabetes and cardiovascular disorders. Unlike obesity, lipedema tissue does not respond well to diet or physical exercise alone. Therefore, in this review we discuss the effect of various dietary supplements that, along with diet and physical exercise, cause fat burning and weight loss, and which could potentially be important in the treatment of lipedema. Indeed, an effective fat burner should convert stored fats into energy, mobilize and break down triglycerides in adipocytes, boost metabolism and inhibit lipogenesis. Common ingredients of fat burning supplements are green tea, caffeine, chromium, carnitine, and conjugated linoleic acid. The use of fat burners could act synergistically with a healthy diet and physical exercise for decreasing adipose tissue deposition in patients with lipedema and resolve related health issues. The effects of fat burners in human studies are sometimes contradictory, and further studies should test their effectiveness in treating lipedema.

Low Efficacy of Genetic Tests for the Diagnosis of Primary Lymphedema Prompts Novel Insights into the Underlying Molecular Pathways.

Lymphedema is a chronic inflammatory disorder caused by ineffective fluid uptake by the lymphatic system, with effects mainly on the lower limbs. Lymphedema is either primary, when caused by genetic mutations, or secondary, when it follows injury, infection, or surgery. In this study, we aim to assess to what extent the current genetic tests detect genetic variants of lymphedema, and to identify the major molecular pathways that underlie this rather unknown disease. We recruited 147 individuals with a clinical diagnosis of primary lymphedema and used established genetic tests on their blood or saliva specimens. Only 11 of these were positive, while other probands were either negative (63) or inconclusive (73). The low efficacy of such tests calls for greater insight into the underlying mechanisms to increase accuracy. For this purpose, we built a molecular pathways diagram based on a literature analysis (OMIM, Kegg, PubMed, Scopus) of candidate and diagnostic genes. The PI3K/AKT and the RAS/MAPK pathways emerged as primary candidates responsible for lymphedema diagnosis, while the Rho/ROCK pathway appeared less critical. The results of this study suggest the most important pathways involved in the pathogenesis of lymphedema, and outline the most promising diagnostic and candidate genes to diagnose this disease.

What's New on Quantitative CT Analysis as a Tool to Predict Growth in Persistent Pulmonary Subsolid Nodules? A Literature Review.

Pulmonary subsolid nodules (SSNs) are observed not infrequently on thin-section chest computed tomography (CT) images. SSNs persisting after a follow-up period of three to six months have a high likelihood of being pre-malignant or malignant lesions. Malignant SSNs usually represent the histologic spectrum of pulmonary adenocarcinomas, and pulmonary adenocarcinomas presenting as SSNs exhibit quite heterogeneous behavior. In fact, while most lesions show an indolent course and may grow very slowly or remain stable for many years, others may exhibit significant growth in a relatively short time. Therefore, it is not yet clear which persistent SSNs should be surgically removed and for how many years stable SSNs should be monitored. In order to solve these two open issues, the use of quantitative analysis has been proposed to define the "tailored" management of persistent SSNs. The main purpose of this review was to summarize recent results about quantitative CT analysis as a diagnostic tool for predicting the behavior of persistent SSNs. Thus, a literature search was conducted in PubMed/MEDLINE, Scopus, and Web of Science databases to find original articles published from January 2014 to October 2019. The results of the selected studies are presented and compared in a narrative way.

Pulmonary metastases from malignant epithelioid schwannoma of the arm presenting as fast-growing subsolid nodules: Report of an unusual case.

Subsolid pulmonary nodules (SSNs) may be the manifestation of benign and malignant conditions. Malignant SSNs usually correspond to the preinvasive or invasive lepidic growth of pulmonary adenocarcinomas. More rarely, malignant SSNs may be the manifestation of primitive pulmonary lymphomas or metastases from extrapulmonary malignancies. In the case of metastases from extrapulmonary malignancies, the SSNs exhibit more aggressive behavior with rapid growth in a short period of time. The present article describes the first case of pulmonary metastases presenting as fast-growing SSNs in a patient with malignant epithelioid schwannoma of the arm.

Two synchronous lung metastases from malignant melanoma: the same patient but different morphological patterns.

Malignant melanoma is an aggressive cancer with a high metastatic potential. Among the multiple sites of metastatic disease, the lung is one of the most frequently involved sites. Typically, pulmonary metastases from malignant melanoma occur as solid nodules. Rarely, pulmonary involvement in metastatic melanoma occurs as subsolid nodules. The present article describes an unusual case of a patient with malignant melanoma that developed two synchronous pulmonary metastases with two different densities on CT images (one solid and the other subsolid) and different morphological patterns on histologic images. The radiologic-pathologic correlation of these two patterns of presentation was also reported.

Five-rooted permanent maxillary second molar: CBCT findings of an extremely rare anatomical variant.

Permanent maxillary second molars (MSMs) are the most difficult teeth to treat endodontically because of their complex root canal system. Most MSMs have 3 roots with 3 root canals; however, variations in the root canal configuration and in the number of roots are common. The presence of extra roots in MSMs has been described by several authors, and the reported incidence of 4-rooted MSMs ranges from 0.98% to 5.6%. However, extremely few cases have been reported in the literature in which a living human subject was found to have a 5-rooted MSM. The present report describes the first case of a 5-rooted MSM in a white European subject diagnosed by cone-beam computed tomography.

Solid Indeterminate Pulmonary Nodules of Less Than 300 mm3: Application of Different Volume Doubling Time Cut-offs in Clinical Practice.

In the British Thoracic Society guidelines for incidental pulmonary nodules, volumetric analysis has become the recommended method for growth assessment in solid indeterminate pulmonary nodules (SIPNs) <300 mm3. In these guidelines, two different volume doubling time (VDT) cut-offs, 400 and 600 days, were proposed to differentiate benign from malignant nodules. The present study aims to evaluate the performance of these VDT cut-offs in a group of SIPNs <300 mm3 which were incidentally detected in a routine clinical setting. During a 7-year period, we retrospectively selected 60 patients with a single SIPN <300 mm3. For each SIPN, the volume and VDT were calculated using semiautomatic software throughout the follow-up period, and the performance of the 400- and 600-day VDT cut-offs was compared. In the selected sample, there were 38 benign and 22 malignant nodules. In this group of nodules, the sensitivity, negative predictive value and accuracy of the 600-day VDT cut-off were higher than those of the 400-day VDT cut-off. Therefore, in the management of SIPNs <300 mm3 which were incidentally detected in a clinical setting, the 600-day VDT cut-off was better at differentiating benign from malignant nodules than the 400-day VDT cut-off, by reducing the number of false negatives.

Solid Indeterminate Pulmonary Nodules Less Than or Equal to 250 mm3: Application of the Updated Fleischner Society Guidelines in Clinical Practice.

BACKGROUND: The latest version of the Fleischner Society guidelines for management of incidental pulmonary nodules was published in 2017. The main purpose of these guidelines is to reduce the number of unnecessary computed tomography (CT) examinations during the follow-up of small indeterminate nodules. OBJECTIVE: The present study aimed to evaluate the performance of these guidelines for management of solid indeterminate pulmonary nodules (SIPNs) ≤ 250 mm3. MATERIALS AND METHODS: During a 7-year period, we retrospectively reviewed the chest CT scans of 672 consecutive patients with SIPNs. The study sample was selected according to the following inclusion criteria: solitary SIPN; diameter ≥ 3 mm; volume ≤ 250 mm3; two or more CT scans performed with the same scanner and same acquisition/reconstruction protocol; thin-section 1-mm images in DICOM format; histologic diagnosis or follow-up ≥ 2 years; and no oncological history. Applying these criteria, a total of 27 patients with single SIPNs ≤ 250 mm3 were enrolled. For each SIPN, the volume and doubling time were calculated using semiautomatic software throughout the follow-up period. For each SIPN, we applied the Fleischner Society guidelines, and the recommended management was compared to what was actually done. RESULTS: A significant volumetric increase was detected in 5/27 (18.5%) SIPNs; all growing nodules were observed in high-risk patients. In these SIPNs, a histologic diagnosis of malignancy was obtained. Applying the Fleischner Society recommendations, all five malignant nodules would have been identified. None of the SIPNs < 100 mm3 in low-risk patients showed significant growth during the follow-up period. The application of the new guidelines would have led to a significant reduction in follow-up CT examinations (Hodges-Lehmann median difference, -2 CT scans; p = 0.0001). CONCLUSION: The application of the updated Fleischner Society guidelines has been shown to be effective in the management of SIPNs ≤ 250 mm3 with a significant reduction in radiation dose.

Three-rooted maxillary first premolars incidentally detected on cone beam CT: an in vivo study.

PURPOSE: To explore the incidence and analyze the morphology of three-rooted maxillary first premolars (MFPs) incidentally detected on cone beam computed tomography (CBCT) scans. METHODS: Of 1328 patients who underwent CBCT scans of the maxilla, only patients with three-rooted MFPs were selected. Morphological features, including the lengths and diameters of palatal, mesiobuccal (MB) and distobuccal (DB) roots, the positions of bucco-palatal (B-P) bifurcations, the distances between root canal bifurcations and cementoenamel junctions (CEJs) and the distances between the apical thirds of the roots, were measured. The canal configuration and the visibility of root canals were also evaluated. RESULTS: A total of 16/1328 (1.2%) patients had one or two three-rooted MFPs, and a total of 22/2656 (0.8%) three-rooted MFPs were enrolled. The lengths and diameters of palatal roots were significantly greater than those of other roots. The positions of B-P bifurcations were located mainly at the middle third of the root. The median distances between root canal bifurcations and CEJs were 3 mm for B-P bifurcations and 5.2 mm for MB-DB bifurcations. The distance between MB and DB roots was significantly shorter than the distances between other root pairs. All teeth had a type VIII canal configuration. Palatal roots exhibited the best visibility of root canals, whereas the worst visibility was observed within DB roots. A gender-related relationship was observed only for the lengths of the roots. CONCLUSIONS: The occurrence of three-rooted MFPs is not unusual; therefore, preoperative CBCT evaluation could be suggested whenever endodontic procedures are planned on an MFP.

Hilly or mountainous surface: a new CT feature to predict the behavior of pure ground glass nodules?

Persistent pure ground-glass nodules (pGGNs) typically show an indolent course with very slow growth rates. These slow-growing lesions exhibit different growth patterns regardless of their initial computed tomography (CT) features. Therefore, predicting the aggressive behavior of pGGNs on initial CT remains a diagnostic challenge. The literature reports that computerized analysis and various quantitative features have been tested to improve the risk stratification for pGGNs. The present article describes the long-term follow-up of two pGGNs with different behavior and introduces, for the first time, a new computerized method of analysis that could be helpful for predicting the future behavior of pGGNs.

Pulmonary adenocarcinomas presenting as ground-glass opacities on multidetector CT: three-dimensional computer-assisted analysis of growth pattern and doubling time.

PURPOSE: We aimed to evaluate the growth pattern and doubling time (DT) of pulmonary adenocarcinomas exhibiting ground-glass opacities (GGOs) on multidetector computed tomography (CT). METHODS: The growth pattern and DT of 22 pulmonary adenocarcinomas exhibiting GGOs were retrospectively analyzed using three-dimensional semiautomatic software. Analysis of each lesion was based on calculations of volume and mass changes and their respective DTs throughout CT follow-up. Three-dimensional segmentation was performed by a single radiologist on each CT scan. The same observer and another radiologist independently repeated the segmentation at the baseline and the last CT scan to determine the variability of the measurements. The relationships among DTs, histopathology, and initial CT features of the lesions were also analyzed. RESULTS: Pulmonary adenocarcinomas presenting as GGOs exhibited different growth patterns: some lesions grew rapidly and some grew slowly, whereas others alternated between periods of growth, stability, or shrinkage. A significant increase in volume and mass that exceeded the coefficient of repeatability of interobserver variability was observed in 72.7% and 84.2% of GGOs, respectively. The volume-DTs and mass-DTs were heterogeneous throughout the follow-up CT scan (range, -4293 to 21928 and -3113 to 17020 days, respectively), and their intra- and interobserver variabilities were moderately high. The volume-DTs and mass-DTs were not correlated with the initial CT features of GGOs; however, they were significantly shorter in invasive adenocarcinomas (P = 0.002 and P = 0.001, respectively). CONCLUSION: Pulmonary adenocarcinomas exhibiting GGOs show heterogeneous growth patterns with a trend toward a progressive increase in size. DTs may be useful for predicting tumor aggressiveness.

Congenital cystic lung disease: prenatal ultrasound and postnatal multidetector computer tomography evaluation. Correlation with surgical and pathological data.

PURPOSE: The aim of this study was to evaluate the diagnostic accuracy of postnatal multidetector computed tomography (MDCT) compared with prenatal ultrasound (US), surgical findings, and histology, in 33 patients with congenital cystic lung disease. METHODS: Thirty-three patients, 17 males and 16 females, were evaluated by MDCT. Twenty-seven of these patients underwent prenatal US between week 18 and 22, and between week 32 and 35 of gestation. Lung lobectomy, segmentectomy, atypical resection, lesion resection were performed in 31 patients and surgical specimens were analysed. RESULTS: Prenatal US and MDCT correctly diagnosed 76.9 and 94 % of the lesions, respectively. Disagreement occurred in six lesions with prenatal US and in two lesions with MDCT. No statistically significant differences were observed between the two techniques (P = 0.122). CONCLUSIONS: As most surgeons consider the surgical resection of these lesions mandatory, our study underscores the essential role of imaging, in particular CT, in providing invaluable preoperative information on congenital cystic lung diseases recognised in uterus.