Frequent Recurrence Research Articles

Comparative analysis of the long-term surgical treatment results of noninvasive thymus gland tumors

The study compared the long-term results of thymectomy from traditional open thoracic/sternotomic and endovideosurgical access in 98 patients with thymus tumors. All patients were divided into two groups depending on the thymectomies performed from various surgical approaches. The control group consisted of 34 patients in whom surgical interventions were performed via the traditional open access, and the main group consisted of 29 patients in whom surgical interventions were performed via the endovideosurgical access. Both groups were comparable by sex, age, concomitant pathology, presence, and severity of clinical signs of myasthenia gravis, tumor size, morphological structure, and progression stage according to the classifications by Masaoka-Koga (1997) and TNM-8 2017. According to the frequency of tumor recurrence and regression of myasthenic disorders within 3 years after surgery, no significant differences were found between the groups (2 (5.9%) and 0, p = 0.27;
 9 (69.2%) and 10 (71.4%), p = 0.52, respectively). Moreover, no significantly significant differences were found in the long-term survival (so-called KaplanMeier survival function) between the two groups. The annual, 3-, 5- and 10-year survival rates in the control group were 100%, 90.3% 2%, 87% 4%, and 87% 4%, and in the video-assisted thymectomy group, the survival rates were 100%, 100%, 100%, and 92.3% 3%, respectively (p = 0.71). In general, the long-term results of endovideosurgical thymectomy with small tumors and the absence of invasion into neighboring anatomical structures do not differ from those of traditional open surgical interventions in terms of the main oncological indicators, namely, long-term survival and frequency of tumor recurrence. The obtained results are consistent with world literature data, according to which the most significant prognostic factor of long-term survival is the stage of tumor progression by TNM. The average 5-year survival rates following radical thymectomy were 90%, 90%, 60%, and 25%, respectively, for TNM stages I, II, III, and IV.

OR23-06 Long Term Outcomes Of Parathyroid Autografts In Primary Hyperparathyroidism

Abstract Disclosure: E. Chuki: None. A. Graf: None. A. Ninan: None. R. Tora: None. T. Abijo: None. N.M. Center: None. N. Nilubol: None. L.S. Weinstein: None. S.K. Agarwal: None. W.F. Simonds: None. S. Jha: None. Background: Autologous implantation of parathyroid tissue is frequently utilized in patients with heritable forms of primary hyperparathyroidism (PHPT). There is sparse data on long-term functional outcome of these grafts and post-graft recurrence of PHPT. Objective: We aimed to investigate the long-term outcome of parathyroid autografts and assess the frequency of post-graft PHPT recurrence. Methods: Retrospective study of patients with PHPT who underwent parathyroid autografts from 1991 to 2020. Results: We identified 115 patients with PHPT who underwent 135 parathyroid autografts. A significant majority (106 of 115 patients, 92%) had a heritable form of PHPT, with MEN1 being the most common (93 of 115 patients, 81%). Median follow-up duration since graft was 10 [4-20] years. 119 (88%) were to brachioradialis, 11 (8%) to sternocleidomastoid and 5 (4%) to deltoid. There were 86 immediate (64%) and 49 delayed (36%) grafts. Of the 135 grafts, 54 (40%) were fully functional at last follow-up, 13 (10%) partially functional, 44 (32%) non-functional while functional status of 24 (18%) grafts could not be ascertained. Age at graft, thymectomy prior to autograft, graft type (delayed/immediate) or duration of cryopreservation did not predict functional outcome. There were 45 (83%) post-graft recurrences of PHPT among 54 fully functional grafts at a median duration of 8 [4-15] years after grafting. Parathyroidectomy was performed in 42/45 but surgical cure was attained in 18/42 (43%) only. 12 of 18 (67%) recurrences were graft-related while the remaining 6 (33%) had a neck or mediastinal source. Median time to recurrence was 16 [11-25] years in neck or mediastinal source versus 7 [2-13] years in graft-related recurrences. Median PTH gradient was significantly higher at 23 [20-27] in graft-related recurrence versus 1.3 [1.2-2.5] in neck or mediastinal source (P = 0.03). Nineteen patients had multiple parathyroid grafts. Median pre-repeat-graft PTH of 7.5 [6.5-18.5] pg/mL with ionized calcium of 1.15 ± 0.145 (reference:1.09-1.30) mmol/L served as an indicator of the need for a repeat graft. Discussion: Post-graft recurrence occurs frequently within the first decade after grafting. Source of excess PTH in post-graft recurrence of PHPT can be challenging to localize. Time to recurrence after graft is significantly shorter and PTH gradient higher for graft-related recurrence. Presentation: Saturday, June 17, 2023

Single-cell transcriptomic analysis of gingivo-buccal oral cancer reveals two dominant cellular programs.

Oral squamous cell carcinoma of the gingivo-buccal region (OSCC-GB) is the most common cancer among men in India, and is associated with poor prognosis and frequent recurrence. Cellular heterogeneity in OSCC-GB was investigated by single-cell RNA sequencing of tumors derived from the oral cavity of 12 OSCC-GB patients, 3 of whom had concomitant presence of a precancerous lesion (oral submucous fibrosis [OSMF]). Unique malignant cell types, features, and phenotypic shifts in the stromal cell population were identified in oral tumors with associated submucous fibrosis. Expression levels of FOS, ATP1A, and DUSP1 provided robust discrimination between tumors with or without the concomitant presence of OSMF. Malignant cell populations shared between tumors with and without OSMF were enriched with the expression of partial epithelial-mesenchymal transition (pEMT) or fetal cell type signatures indicative of two dominant cellular programs in OSCC-GB-pEMT and fetal cellular reprogramming. Malignant cells exhibiting fetal cellular and pEMT programs were enriched with the expression of immune-related pathway genes known to be involved in antitumor immune response. In the tumor microenvironment, higher infiltration of immune cells than the stromal cells was observed. The T cell population was large in tumors and diverse subtypes of T cells with varying levels of infiltration were found. We also detected double-negative PLCG2+ T cells and cells with intermediate M1-M2 macrophage polarization. Our findings shed light on unique aspects of cellular heterogeneity and cell states in OSCC-GB.

Depleting ANTXR1 suppresses glioma growth via deactivating PI3K/AKT pathway

ABSTRACTGliomas are commonly known as primary brain tumors and associated with frequent recurrence and an unsatisfactory prognosis despite extensive research in the underlying molecular mechanisms. We aimed to examine the role of ANTXR1 in glioma tumorigenesis and explore its downstream regulatory mechanism. ANTXR1 expression in clinical specimens and its relationship with some pathological characteristics were detected using immunohistochemical staining. After silencing/upregulating ANTXR1 through lentiviral transfection in glioma cell lines, qRT-PCR and western blotting were used to examine mRNA and protein levels, and cell phenotype was also detected. ANTXR1-knockdown and -overexpression cells were then processed by AKT activator and PI3K inhibitor, respectively, to verify downstream PI3K/AKT pathway regulated by ANTXR1. Xenograft nude mice models were constructed to verify the role of ANTXR1 in vivo. We found overexpression of ANTXR1 in both cell lines in comparison with those in normal brain tissues. Glioma cell growth and migratory ability were dramatically impaired as a result of silencing ANTXR1 by shANTXR1 lentiviruses. ANTXR1 blockade also accelerated cell apoptosis and held back cell cycle via targeting G2 phrase during cell mitosis. In vivo xenograft models verified in vitro findings above. Further exploration disclosed that AKT activator promoted anti-tumor effects mediated by ANTXR1 knockdown, while PI3K inhibitor limited pro-tumor effects mediated by ANTXR1 overexpression, indicating that ANTXR1 functioned in glioma cells through regulating PI3K/AKT pathway. ANTXR1 could play an indispensable role in glioma tumorigenesis via activating PI3K/AKT-mediated cell growth. Our study provides a theoretical basis for targeting ANTXR1 as a molecular target in glioma clinical therapeutics.

Anxiolytic-like action of 3-((4-methoxyphenyl)selanyl)-2-phenylbenzofuran (SeBZF3) in mice: A possible contribution of the serotonergic system

Anxiety disorders, characterized by high prevalence rates, cause psychiatric disabilities and are related to impairments in serotoninergic system function. Frequent anxiety recurrence, resistance, and drug adverse effects have driven searches for new therapies. We initially evaluated the anxiolytic-like activity of 3-selanyl-benzo[b]furan compounds (SeBZF1–5) (50 mg/kg, i.g.) in male Swiss mice using the light-dark test (LDT). The compound 3-((4-methoxyphenyl)selanyl)-2-phenylbenzofuran (SeBZF3) exhibited anxiolytic-like activity. SeBZF3 anxiolytic-like effects were also observed in the novelty-suppressed feeding test (NSFT) (50 mg/kg) and elevated plus-maze test (EPMT) (25 and 50 mg/kg). In the EPMT, anxiolytic-like effects of SeBZF3 (50 mg/kg) were abolished by pretreatment with p-chlorophenylalanine, a selective tryptophan hydroxylase inhibitor (100 mg/kg, i.p. for 4 days), suggesting the involvement of serotonergic mechanisms. Furthermore, we conducted experiments to investigate the synergistic effects of SeBZF3 subeffective doses (5 mg/kg, i.g.) in combination with fluoxetine (a selective serotonin reuptake inhibitor, 5 mg/kg, i.p.) or buspirone (a partial agonist of the 5-HT1A receptor, 2 mg/kg, i.p.). This coadministration resulted in pronounced synergistic effects. We also examined the effects of repeated oral treatment with SeBZF3 at doses of 1 and 5 mg/kg over 14 days and both reduced anxiety signals. In vitro and ex vivo findings revealed that SeBZF3 inhibited cerebral MAO-A activity. These findings collectively imply the potential involvement of serotonergic mechanisms in the anxiolytic-like activity of SeBZF3 in mice. These data offer contributions to the research field of organoselenium compounds and anxiolytics, encouraging the broadening of the search for new effective drugs while offering improved side effect profiles.

Outcomes of the distal rectal cancer treatment depending on the type of sphincter-sparing surgery

Introduction: The increase in mid-ampullary and lower ampullary rectal cancer with disappointing treatment results requires ongoing discussion, research, and improvement of the complex treatment. Materials and methods: We analyzed the results of complex treatment in 442 patients with stages II–III mid-ampullary and lower ampullary rectal cancer that underwent three types of sphincter-sparing surgeries, including low anterior resection (LAR), intersphincteric resection (ISR), and abdomino-anal resection of the rectum (AAR) at the second stage of complex treatment. Results: There was a significant difference between groups in terms of surgery type selection based on the distance from the tumor to the dentate line. When the tumor was located at a distance of 30 mm or less from the dentate line, LAR was performed in 16.4% of cases, whereas ISR and AAR were used in 96.58 and 58.09% of cases, respectively, which is statistically significant (P<0.001). Preventive stoma was used in 78.87% of LAR, 5.9% of ISR, and 6.62% of AAR, which had a significant difference (P<0.001). In the structure of postoperative complications, a group of typical complications (ІІІ–IV) was identified for the types of operations performed. Their frequency when performing LAR was 18.2%, ISR – 7.7%, and AAR – 8.1%, which was statistically significant (P=0.003). The frequency of local recurrences, depending on the type of surgery was not statistically significant (P>0.05), but had a direct correlation with the recurrence-free survival curves. Relapse-free and overall (3 years and 5 years) survival depending on the type of sphincter-preserving surgery did not have a significant difference according to the log-rank test. Conclusion: The more types of surgical intervention surgeons have at their disposal, the more rational it is to select the one that will ensure the best treatment results.

Exploiting targeted nanomedicine for surveillance, diagnosis, and treatment of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the cancers that has the highest morbidity and mortality rates. In clinical practice, there are still many limitations in surveilling, diagnosing, and treating HCC, such as the poor detection of early HCC, the frequent post-surgery recurrence, the low local tumor control rate, the therapy resistance and side effects. Therefore, improved, or innovative modalities are urgently required for early diagnosis as well as refined and effective management. In recent years, nanotechnology research in the field of HCC has received great attention, with various aspects of diagnosis and treatment including biomarkers, ultrasound, diagnostic imaging, intraoperative imaging, ablation, transarterial chemoembolization, radiotherapy, and systemic therapy. Different from previous reviews that discussed from the perspective of nanoparticles' structure, design and function, this review systematically summarizes the methods and limitations of diagnosing and treating HCC in clinical guidelines and practices, as well as nanomedicine applications. Nanomedicine can overcome the limitations to improve diagnosis accuracy and therapeutic effect via enhancement of targeting, biocompatibility, bioavailability, controlled releasing, and combination of different clinical treatment modalities. Through an in-depth understanding of the logic of nanotechnology to conquer clinical limitations, the main research directions of nanotechnology in HCC are sorted out in this review. It is anticipated that nanomedicine will play a significant role in the future clinical practices of HCC.

Treatment Outcomes and Prognostic Factors in N3 Stage Gastric Cancer After Curative Resection: A Real World Data.

N3 gastric cancer is characterized by a fairly high lymph node metastasis burden and poor outcome despite optimal therapy. Given the limitations of TNM classification, a comprehensive evaluation tool is necessary to predict the prognosis of patients with N3 gastric cancer who underwent curative surgery. This study aims to explore the outcomes and clinicopathologic prognostic factors affecting the overall survival (OS) of patients with N3 gastric cancer after surgery. Data on patients with N3 gastric cancer who underwent (sub)total gastrectomy and regional lymph node dissection between November 2005 and September 2018 (n =169) were analyzed by Cox regression to determine the independent prognostic factors for OS. The multivariable analysis established that gender, patient performance status, metastatic lymph node ratio (MLNR), tumor grade, and adjuvant chemotherapy are significantly associated with OS. The five-year OS of the study population was 15%. Adjuvant chemoradiotherapy was applied to 72% of the patients, which resulted in an improvement in recurrence-free survival but not OS. Recurrence occurred in 103 (75%) patients, in which the most frequent recurrence site was distant metastasis. Male gender, poor performance status, grade 3 tumor, MLNR >0.37, and not receiving adjuvant chemotherapy are predictors of poor prognosis in N3 gastric cancer after curative resection. Considering the high recurrence rates of this group, prospective studies are needed to optimize treatment strategies.

Refining Surveillance Guidelines after SBRT for Early-Stage Lung Cancer

Stereotactic Body Radiation Therapy (SBRT) is a popular treatment for patients with early-stage non-small cell lung cancer (NSCLC). After treatment, NCCN guidelines suggest 3-6-month imaging surveillance up to year 3, every 6 months in years 3-5, and yearly after 5 years. The Delphi Consensus Study recommends annual screening in years 2-5. While patients are more likely to locally recur up to two years after treatment there remains a paucity of data on the benefit of long-term surveillance. We therefore evaluated a cohort of NSCLC patients to evaluate the utility and frequency of both short- and long-term surveillance. A total of 224 patients with early-stage NSCLC treated with SBRT between 2014-2019 at a single institution were retrospectively evaluated. Patients with nodal disease, treated with >8 fractions, or metastatic disease at time of SBRT were excluded. Any cross-sectional imaging of the chest for each patient after SBRT was reviewed for evidence of recurrence or new malignancy. Recurrence or new malignancy was defined radiographically and/or pathologically. The median scan interval (MSI) was calculated using the time between surveillance scans. The MSI between patients with or without new disease was compared by t-test. Frequency of recurrence between patients with <T2 or > = T2 disease was compared using chi squared analysis. A total of 224 patients were reviewed and 168 were included in the analysis. 919 scans were performed, 800 as scheduled surveillance scans and 119 for other indications. Median number of scans per patient was 5 (IQR 3-13), with a max of 15 scans. The MSI was 5 months (IQR 3-6) for up to 3 years after treatment, 8 months (IQR 6-12) between 3-5 years after treatment, and 12 months (IQR 11-13) ≥5 years after treatment. There was no significant difference in MSI between patients that did or did not develop new/recurrent disease. 47% of patients with <T2 had new disease compared to 63% with > = T2 tumors (p = 0.10). All 3 patients with T3 disease recurred or had new malignancy identified on 2, 7, and, 36-month scans. 67 instances of new disease were found on 521 scans (13%) during years 1-3, 12 instances on 70 scans (17%) years 3-4, and 5 found on 11 scans (45%) after 5 years. Of 84 total instances of new disease, representing 50% evaluable patients, 75 were discovered on surveillance scans compared to 9 on non-surveillance scans. The MSI for patients in this cohort aligns with published guidelines. Half of the patients developed new disease with the vast majority discovered on surveillance scans. Higher chance of new disease in larger tumors would suggest not all patients benefit from the same scan interval with some patients receiving up to 15 diagnostic scans during follow up. With patients continuing to recur >5 years after treatment, scan frequency, radiation exposure, and probability of recurrence should all be considered in comprehensive surveillance guidelines.

Parathyroid Retrospective Analysis of Neoplasms Incidence (pTRANI Study): An Italian Multicenter Study on Parathyroid Carcinoma and Atypical Parathyroid Tumour.

Parathyroid cancer (PC) is a rare sporadic or hereditary malignancy whose histologic features were redefined with the 2022 WHO classification. A total of 24 Italian institutions designed this multicenter study to specify PC incidence, describe its clinical, functional, and imaging characteristics and improve its differentiation from the atypical parathyroid tumour (APT). All relevant information was collected about PC and APT patients treated between 2009 and 2021. Among 8361 parathyroidectomies, 351 patients (mean age 59.0 ± 14.5; F = 210, 59.8%) were divided into the APT (n = 226, 2.8%) and PC group (n = 125, 1.5%). PC showed significantly higher rates (p < 0.05) of bone involvement, abdominal, and neurological symptoms than APT (48.8% vs. 35.0%, 17.6% vs. 7.1%, 13.6% vs. 5.3%, respectively). Ultrasound (US) diameter >3 cm (30.9% vs. 19.3%, p = 0.049) was significantly more common in the PC. A significantly higher frequency of local recurrences was observed in the PC (8.0% vs. 2.7%, p = 0.022). Mortality due to consequences of cancer or uncontrolled hyperparathyroidism was 3.3%. Symptomatic hyperparathyroidism, high PTH and albumin-corrected serum calcium values, and a US diameter >3 cm may be considered features differentiating PC from APT. 2022 WHO criteria did not impact the diagnosis.

Treatment of genital prolapse in elderly women with genitourinary infection

Relevance of the study. Genital prolapse (GP) is a disease that unites a group of disorders of the muscular and ligamentous apparatus of the uterus and vagina, which lead to prolapse and prolapse of the internal genital organs. The incidence of HP in women over 50 reaches 50%, and among elderly and senile women, it increases to 60-70%. Frequent recurrence and the development of septic complications are characterised by urinary tract infections that occur against the background of genital abnormalities, hormone deficiency in the postmenopausal period, diabetes mellitus, asymptomatic bacteriuria, neurogenic bladder dysfunction, urinary incontinence, and surgical interventions on the genital or urinary system.The aim of the study is to optimize the treatment of genital prolapse (GP) in elderly women with urinary and genital infections. Materials and methods. We examined 70 elderly patients, including 20 (28.6%) with GP and infectious lesions of the urinary and genital organs (main group), 30 (42.8%) with GP without infectious lesions of the urinary and genital organs (comparison group), 20 (28.6%) women without gynaecological diseases and extragenital pathology (control group). The severity of the inflammatory process was assessed based on the study of complaints, anamnesis, and laboratory results. The degree of GP was determined using the POP-Q quantitative assessment system. The surgical intervention included transvaginal extirpation of the uterus without appendages, anterior colporrhaphy, colpoperineorrhaphy with levatoroplasty, and sacrospinal colpopexy. Before using the «Polymesh» synthetic mesh endoprosthesis, in order to minimise infectious complications caused by the use of synthetic prostheses, hydrodissection was performed with 0.9% sodium chloride saline (200 ml) with the addition of a third-generation cephalosporin antibiotic (1 g). Results of the study. Patients underwent uterine extirpation without vaginal appendages, unilateral sacrospinal colpopexy, anterior colporrhaphy, colpoperineorrhaphy with levatorrhaphy (in 6 (30%) women of the first group and 13 (43%) - of the second group). Uterine extirpation without vaginal appendages, sacrospinal colpopexy on the left using the «Polymesh» mesh prosthesis, anterior colporrhaphy, colpoperineorrhaphy with levatoroplasty - in 14 (70%) women of the first group and 17 (57%) of the second group. In case of stress urinary incontinence, a mid-urethral sling procedure was additionally performed (6 patients in the first group and 5 in the second). Women with genitourinary infection mainly underwent transvaginal uterine extirpation with unilateral sacrospinal colpopexy and the use of a synthetic mesh prosthesis «Polymesh». The volume of the operation in the form of uterine extirpation using the «Polymesh» prosthesis is due to the reliable effect of the mesh prosthesis in order to prevent the recurrence of the disease compared to sacrospinal colpopexy (1/4% of cases). Conclusions. Surgical treatment of genital prolapse in women with infectious lesions of the urinary and genital organs by using the «Polymesh» mesh prosthesis for colposacropexy after transvaginal uterine extirpation increases the effectiveness of its treatment, reducing the number of recurrences of the disease.

Клинико-анамнестические факторы рецидивирующих полипов эндометрия в репродуктивном возрасте

The prevalence of endometrial polyps (EP) ranges from 7.8 to 34.9%, and in the group of patients with symptoms reaches 24%. The natural course of EP is unclear, the frequency of spontaneous regression of EP varies from 6.3% to 57.1%, but it is impossible to accurately predict the nature of the growth of an individual polyp and the probability of regression. A successful operation does not guarantee against recurrence of the disease: according to various authors, the frequency of postoperative recurrence of EP varies from 5.6% to 43.6%, depending on the duration of observa-tion and the nature of polyps. To improve the results of EP treatment, to determine the target groups for hysteroscopic polypectomy, it is impor-tant to have an understanding of the risk factors for recurrence of EP. The analysis of scientific publications in the databases eLibrary, PubMed, Cochrane Library, Science Direct was performed, according to the keywords endometrial polyps/endometrial polyp, recurrence/recurrence, risk factors/risk factors, reproductive age/reproductive age, premenopausal age/premenopausal age for 2013–2023. The obtained results of the liter-ature analysis allow us to conclude about the influence of age, multiple nature of polyps, chronic endometritis on the risk of recurrence of EP. In addition, other factors may be involved in the development of recurrent polyps. For a more accurate assessment of the contribution of various risk factors to the recurrence of EP, it is necessary to perform high-quality scientific research. The purpose of the work: to analyze the available literature data and summarize the information received to date on the clinical and anamnestic risk factors of EP.

The Frequency of Differentiated Thyroid Cancer Recurrence in 2302 Patients With Excellent Response to Primary Therapy.

Discrepant data on the recurrence rate of differentiated thyroid cancer (DTC) are reported. To evaluate the frequency and risk factors of true recurrence in DTC patients with excellent responses (ExR) to initial therapy. A retrospective analysis of the 2302 consecutive DTC patients with ExR to primary therapy, treated during 24 years at single center. The percentage of recurrence and cumulative recurrence rate (CRR) were analyzed. Risk factors for recurrence for patients with papillary thyroid cancer (PTC) were investigated and methods for establishing a diagnosis of recurrence were evaluated. Of DTC patients, 32 (1.4%) experienced recurrence. PTC patients with recurrence were more likely to have younger age (P = .0182), larger tumor size (P = .0013), lymph node metastases (P = .0013), incomplete resection (P = .0446), higher ATA risk (P = .0002), and had more frequently been treated with 131I (P = .0203). CRRs at 5, 10, 15, 20, and 24 years after surgery were 1.2%, 1.9%, 2.5%, 2.9%, and 2.9%, respectively. The CRRs according to histological type were highest for poorly differentiated thyroid cancer (PDTC), lower for oncocytic (OTC) and follicular thyroid cancer (FTC), and lowest for PTC. Most recurrences occurred within the first 5 years of observation. The most effective method for detecting local recurrence was ultrasonography with fine needle aspiration cytology, and for distant metastases, 18F-FDG PET. True recurrence is rare in DTC patients. PTC patients with ExR to primary therapy and N0/Nx can be dismissed from oncological follow-up. Despite ExR to primary therapy, DTC patients with N1, and PDTC, OTC, FTC should remain under oncological follow-up.

Nature Management and Adverse Hydrometeorological Phenomena in Northern Bukovina in the XVIII – Early XX Centuries

Climate change remains the most pressing issue in the world today, resulting in the intensification of adverse hydrometeorological phenomena. In the regional context, local peculiarities of climate change are important, as each region is characterized by a certain set of adverse phenomena. The purpose of the article is to analyze the distribution and frequency of recurrence of adverse hydrometeorological phenomena, as well as their impact on the natural resources of Northern Bukovina in the eighteenth and early twentieth centuries; changes in natural resources use within the plains, foothills and mountains of Northern Bukovina. In accordance with the purpose, a comparative characterization of the past and present climate of Northern Bukovina was carried out, documentary data on the manifestation of adverse phenomena in the eighteenth - early twentieth centuries in Northern Bukovina were analyzed. The frequency of these phenomena is also revealed; the most recurrent and widespread within the region are highlighted; the years with adverse events that caused the greatest damage are described; the largest floods and droughts are indexed by the scale of their consequences; changes in the use of natural resources in Northern Bukovyna are considered and the impact of floods and droughts on natural resources is revealed. The main unfavorable hydrometeorological phenomena within Northern Bukovyna in the eighteenth and early twentieth centuries are considered. Data from the archives of the Austro-Hungarian period show that the most recurrent and characteristic of these events are: droughts, floods, heavy rainfall with thunderstorms, hail and storms, cold winters. Documentary data on droughts and floods correlate with instrumental data. Keywords: climate, nature management, adverse hydrometeorological events, floods, droughts, Northern Bukovyna.

Urban Dystopia on Screen: The City, Architecture and Power in the Contemporary Science Fiction Film

This paper investigates the urban, architectural and spatial mise-en-scène of major western 21st-century science fiction film dystopias portraying urban societies under totalitarian rule. While extensive scholarship exists on architecture, the city and power and similarly on architecture, the city and film, the triad of architecture/city, film and power remains under-researched. This paper therefore concentrates on how power is mediated through built form on screen. It also investigates whether recurring visualizations and meaning(s) of built form concerning power can be observed. Considering key works about the built environment and its relation to power, this study also uses a semiological approach in order to assess the symbolic-metaphorical use of urban, architectural and spatial form. We assume that producers, directors, set-designers, screenwriters on one side and the film audience on the other ‘speak a similar language’ and share cultural codes and symbols. The frequent recurrence of specific urban, architectural and spatial visualizations in science fiction films which mediate specific meanings of power may be proof of a widespread, conscious or subconscious reading of these visualizations and understanding of their meaning(s) with regards to power – meanings which may therefore be deeply rooted in the culture of western societies.

Cardiopulmonary Morbidity in Adults Born With Congenital Diaphragmatic Hernia.

Studies concerning cardiopulmonary outcomes of adults born with congenital diaphragmatic hernia (CDH) are sparse. Moreover, they don't include participants who have been treated with extracorporeal membrane oxygenation (ECMO) during the neonatal period. This study evaluated the cardiopulmonary morbidities in young adults born with CDH. We assessed 68 participants between the ages of 18 and 30 years. The assessment included auxology assessment, lung function tests, pulmonary imaging, cardiopulmonary exercise testing, and echocardiography. Lung function parameters in the overall group were significantly worse than normal values. Mean (SD) scores postbronchodilator forced expiratory volume in 1 second were -2.91 (1.38) in the ECMO-treated and -1.20 (1.53) in the non-ECMO-treated participants. Chest computed tomography scans showed mild to moderate abnormal lung structure in all ECMO-treated participants, and to a lesser extent in non-ECMO treated participants. A recurrent diaphragmatic defect was observed in 77% of the ECMO-treated group and in 43% of the non-ECMO-treated group. Except for 2 cases with acute symptoms, no clinical problems were noted in cases of recurrence. Cardiopulmonary exercise testing revealed mean (SD) percentage predicted peak oxygen consumption per kilogram of 73 (14)% and 88 (16)% in ECMO-treated and non-ECMO-treated participants, respectively. The mean (SD) workload was normal in the non-ECMO-treated group (111 [25]% predicted); in the ECMO-treated group, it was 89 (23)%. Cardiac evaluation at rest revealed no signs of pulmonary hypertension. In young adults who survived treatment of CDH, significant pulmonary morbidity, reduced exercise capacity, and frequent hernia recurrence should be anticipated. Lifelong follow-up care, with the emphasis on prevention of further decline, is to be recommended.

Molecular Markers for Bladder Cancer Screening: An Insight into Bladder Cancer and FDA-Approved Biomarkers.

Bladder cancer is one of the most financially burdensome cancers globally, from its diagnostic to its terminal stages. The impact it imposes on patients and the medical community is substantial, exacerbated by the absence of disease-specific characteristics and limited disease-free spans. Frequent recurrences, impacting nearly half of the diagnosed population, require frequent and invasive monitoring. Given the advancing comprehension of its etiology and attributes, bladder cancer is an appealing candidate for screening strategies. Cystoscopy is the current gold standard for bladder cancer detection, but it is invasive and has the potential for undesired complications and elevated costs. Although urine cytology is a supplementary tool in select instances, its efficacy is limited due to its restricted sensitivity, mainly when targeting low-grade tumors. Although most of these assays exhibit higher sensitivity than urine cytology, clinical guidelines do not currently incorporate them. Consequently, it is necessary to explore novel screening assays to identify distinctive alterations exclusive to bladder cancer. Thus, integrating potential molecular assays requires further investigation through more extensive validation studies. Within this article, we offer a comprehensive overview of the critical features of bladder cancer while conducting a thorough analysis of the FDA-approved assays designed to diagnose and monitor its recurrences.

Circulating Tumor DNA Dynamics as Prognostic Markers in Locally Advanced and Metastatic Esophageal Squamous Cell Carcinoma

Esophageal squamous cell carcinoma (ESCC) is a deadly disease with frequent recurrence. There are unmet needs for prognostic biomarkers for dynamically monitoring disease progression and detecting minimal residual disease. To examine whether circulating tumor DNA is clinically useful as a prognostic biomarker for ESCC recurrence and patient survival. This single-center, population-based cohort study consecutively enrolled 147 patients receiving curative (n = 74) or palliative (n = 73) treatment at the surgery and clinical oncology departments of Queen Mary Hospital in Hong Kong from August 1, 2016, to September 31, 2021. Patients were followed up for 2 years. Plasma samples were collected at different longitudinal time points for a prospective circulating tumor DNA (ctDNA) next-generation sequencing profiling study of 77 actionable genes. Patients were treated with up-front surgery, neoadjuvant chemoradiotherapy plus surgery with or without adjuvant therapy, or palliative chemotherapy (CT). Detection of circulating tumor DNA (ctDNA), progression-free survival (PFS), and overall survival (OS). A total of 478 serial plasma samples from 147 patients with locoregional or metastatic ESCC were prospectively analyzed. Among the 74 patients in the curative group (median [range] age, 66 [46-85] years; 56 [76.0%] male), 44 (59.5%) relapsed and 36 (48.6%) died. For patients receiving curative surgical treatment, a high ctDNA level (hazard ratio [HR], 7.84; 95% CI, 1.87-32.97; P = .005) and ctDNA alterations (HR, 5.71; 95% CI, 1.81-17.97; P = .003) at 6 months postoperation were independently associated with poor OS. Among patients receiving neoadjuvant chemoradiotherapy, postneoadjuvant ctDNA alterations were associated with poor PFS (HR, 3.16; 95% CI, 1.17-8.52; P = .02). In the 73 patients in the palliative group (median [range] age, 63 [45-82] years; 63 [86.0%] male), 71 (97.3%) had disease relapse and 68 (93.2%) died. Detectable pre-CT NFE2L2 alterations were independently associated with PFS (HR, 2.99; 95% CI, 1.35-6.61; P = .007) and OS (HR, 28.39; 95% CI, 7.26-111.03; P = 1.52 × 10-6), whereas high ctDNA levels (HR, 2.41; 95% CI, 1.18-4.95; P = .02) and alterations in pre-cycle III ctDNA (HR, 1.99; 95% CI, 1.03-3.85; P = .04) showed weaker associations with PFS. Alterations in pre-CT ctDNA were independently associated with OS (HR, 4.46; 95% CI, 1.86-10.69; P = 7.97 × 10-4). The findings of this cohort study indicate that prognostic models incorporating ctDNA features are useful in ESCC. Both ctDNA level and NFE2L2 alterations pre-CT and before cycle III were found to be important prognostic factors in palliative groups, and ctDNA alterations after treatment and at 6 months after surgery may define high-risk groups for recurrence in the curative group. High-risk patients can benefit by a timely switch to the next therapeutic options.

Retrospective evaluation of ceruminous gland tumors confined to the external ear canal of dogs and cats treated with biopsy and CO2 laser ablation.

Treatments currently available for ceruminous gland tumors include surgery and radiation therapy, which come with high financial costs and frequent complication and recurrence rates. To evaluate the treatment, response, complication, and recurrence of ceruminous gland tumors confirmed with biopsy and ablated using CO2 laser. Retrospective review of medical records from Iowa State Universityand the University of Illinois between January 1, 2016 and December 31, 2021. Electronic medical records were evaluated for a histopathologically confirmed ceruminous gland tumor via video-otoscopic aided biopsy and subsequent CO2 laser ablation. Signalment, tumor type, size, location within the ear canal, length of time tumor was present before presentation, advanced imaging, and follow-up including recurrence were assessed. Fourteen ceruminous gland adenomas (4 dogs, 10 cats) and 12 ceruminous gland adenocarcinomas (7 dogs, 5 cats) were identified. Bacterial otitis externa was present in 4/26 (15%) animals. Recurrence was identified in 1/14 (7%) ceruminous gland adenomas and 1/12 (8%) ceruminous gland adenocarcinomas. Video-otoscopic aided biopsy and CO2 laser ablation of ceruminous gland tumors in dogs and cats is a viable treatment option with low recurrence and complication rates with CO2 laser ablation.

Recurrence patterns of acute colonic diverticulitis among patients admittedto Benghazi Medical Center, Benghazi, Libya: A retrospective and hospital-based study

Background: The normal pattern of acute colonic diverticulitis is still unknown, and prophylactic surgery after conservative treatment of diverticulitis is a topic of growing debate. The aim of this study was to investigate the patterns and frequency of recurrences and the likelihood of complications in conservatively treated uncomplicated and complicated diverticulitis in our epidemiological setting. Methods: This retrospective study was conducted to investigate 98 inpatients admitted to Benghazi Medical Center with acute colonic diverticulitis, between February 2021 and August 2022. Acute diverticulitis discharge summaries were reviewed to identify eligible patients, and their medical records were meticulously reviewed retrospectively to confirm that their clinical presentation was consistent with colonic diverticulitis. Results: A retrospective study of 98 patients with acute colonic diverticulitis found that uncomplicated diverticulitis was associated with younger age, better 2-year survival rates, and more conservative management. Recurrence rates were almost similar between uncomplicated and complicated diverticulitis (23% vs. 25%) and typically occurred within 12 months of the initial attack. Surgical intervention was necessary for patients with perforations, while conservative management was used for other cases. Complications included abscesses in 44% of cases and perforations in 38% of cases. Conclusion: This study found that acute diverticulitis has a low recurrence rate and a limited propensity for progression into complications. It is recommended that elective surgery is used as a preventive measure against recurrences and associated complications. These findings have implications for clinical practice.