T2 Cases Research Articles

Long-Term Trajectories of Postoperative Recovery in Younger and Older Veterans

Major surgery sometimes involves long recovery or even permanent institutionalization. Little is known about long-term trajectories of postoperative recovery, as surgical registries are limited to 30-day outcomes and care can occur across various institutions. To characterize long-term postoperative recovery trajectories. This retrospective cohort study used Veterans Affairs (VA) Surgical Quality Improvement Program data (2016 through 2019) linked to the Residential History File, combining data from the VA, Medicare/Medicaid, and other sources to capture most health care utilization by days. Patients were divided into younger (younger than 65 years) or older (65 years or older) subgroups, as Medicare eligibility is age dependent. Latent-class, group-based trajectory models were developed for each group. These data were analyzed from February 2023 through August 2024. Surgical care in VA hospitals. Days elsewhere than home (DEH) were counted in 30-day periods for 275 days presurgery and 365 days postsurgery. A 5-trajectory solution was optimal and visually similar for both age groups (cases: 179 879 younger [mean age (SD) 51.2 (10.8) years; most were male [154 542 (83.0%)] and 198 803 older [mean (SD) age, 72.2 (6.0) years; 187 996 were male (97.6%)]). Most cases were in trajectories 1 and 2 (T1 and T2). T1 cases returned home within 30 days (younger, 74.0%; older, 54.2%), while T2 described delayed recovery within 30 to 60 days (younger, 21.6%; older, 35.5%). Trajectory 3 (T3) and trajectory 4 (T4) were similar for the first 30 days postsurgery, but subsequently separated with T3 representing protracted recovery of 6 months or longer (younger, 2.7%; older, 3.8%) and T4 indicating long-term loss of independence (younger, 1.3%; older, 5.2%). Few (trajectory 5) were chronically dependent, with 20 to 30 DEH per month before and after surgery (younger, 0.4%; older, 1.3%). In this study, trajectory models demonstrated clinically meaningful differences in postoperative recovery that should inform surgical decision-making. Registries should include longer-term outcomes to enable future research to distinguish patients prone to long-term loss of independence vs protracted, but meaningful recovery.

Exploring Molecular Signatures in Early-Stage Pancreatic Ductal Adenocarcinoma: Implications for Patient Management and Therapeutic Strategies

Abstract Introduction/Objective Pancreatic ductal adenocarcinoma (PDAC) poses significant challenges to patient survival, predominantly due to its tendency for late-stage diagnosis and high rates of post-surgical cancer recurrence. Therefore, a comprehensive understanding of the molecular characteristics associated with the early stages of PDAC is imperative. This understanding holds the potential to improve patient treatment strategies by enabling targeted interventions and personalized therapies. Methods/Case Report Initially, RNA-seq datasets of early-stage PDAC cases (stages IA, IB, IIA, and IIB, all without distant metastasis; M0) were extracted from the GEO database. Subsequently, the datasets were analyzed in four distinct groups, and differentially expressed genes were identified within each group. Group 1 compared T1T2 cases with T3 cases (T: primary tumor), irrespective of N status (N: regional lymph nodes), while group 2 compared N0 cases with N1 cases, regardless of T status. Group 3 included comparisons between T1T2N0 cases and T3N0 cases, and group 4 compared T1T2N1 cases with T3N1 cases. Utilizing a Venn diagram, commonalities between gene expression profiles were isolated. Afterward, gene ontology and signaling pathways were determined using KEGG and Enrichr. Finally, a protein network was constructed, and the proteins were evaluated using the GEPIA and TCGA clinical databases. Results (if a Case Study enter NA) The study encompassed a total of 43 cases, with 25 (58.1%) being male and 18 (41.9%) female. The mean age of the participants was 64.4 years. In group 1, the expression levels of MUC5AC, AKAP13, and SPG7 were significantly upregulated in T3 cases. In group 2, STAB1, PDLIM1, and MTUS1 emerged as the top upregulated genes in N1 cases. Group 3 exhibited notable upregulation of CCNL2, CEACAM6, and TSPAN3 in T3N0 cases, while group 4 demonstrated marked upregulation of LTBR, AKAP12, and BOP1 in T3N1 cases. These genes exhibited diverse functions in PDAC progression. They contributed to the regulation of gene expression and cell cycle progression, modulating cell proliferation, inhibiting tumor growth, regulating cell signaling, and were involved in cytoskeletal organization. Conclusion The upregulated genes in cases with the T3 and/or N1 staging components may shed light on the potential mechanisms of progression from stage IA/B to stage IIA/B in PDAC cases. Furthermore, the identified genetic alterations may hold potential therapeutic and prognostic applications for future use in the early stages of PDAC.

Evaluation of the New York City COVID-19 case investigation and contact tracing program: a cascade of care analysis

BackgroundNew York City (NYC) was the first COVID-19 epicenter in the United States and home to one of the country’s largest contact tracing programs, NYC Test & Trace (T2). Understanding points of attrition along the stages of program implementation and follow-up can inform contact tracing efforts for future epidemics or pandemics. The objective of this study was to evaluate the completeness and timeliness of T2 case and contact notification and monitoring using a “cascade of care” approach.MethodsThis cross-sectional study included all SARS-CoV-2 cases and contacts reported to T2 from May 31, 2020 to January 1, 2022. Attrition along the “cascade of care” was defined as: (1) attempted, (2) reached, (3) completed intake (main outcome), (4) eligible for monitoring, and (5) successfully monitored. Timeliness was assessed: (1) by median days from a case’s date of testing until their positive result was reported to T2, (2) from result until the case was notified by T2, and (3) from a case report of a contact until notification of the contact.ResultsA total of 1.45 million cases and 1.38 million contacts were reported to T2 during this period. For cases, attrition occurred evenly across the first three cascade steps (~-12%) and did not change substantially until the Omicron wave in December 2021. During the Omicron wave, the proportion of cases attempted dropped precipitously. For contacts, the largest attrition occurred between attempting and reaching (-27%), and attrition rose with each COVID-19 wave as contact volumes increased. Attempts to reach contacts discontinued entirely during the Omicron wave. Overall, 67% of cases and 49% of contacts completed intake interviews (79% and 57% prior to Omicron). T2 was timely, with a median of 1 day to receive lab results, 2 days to notify cases, and < 1 day to notify contacts.ConclusionsT2 provided a large volume of NYC residents with timely notification and monitoring. Engagement in the program was lower for contacts than cases, with the largest gap coming from inability to reach individuals during call attempts. To strengthen future test-and-trace efforts, strategies are needed to encourage acceptance of local contact tracer outreach attempts.

INCIDENTALLY VS. NON-INCIDENTALLY DIAGNOSED PAPILLARY THYROID CARCINOMA: ARE THERE DIFFERENCES?

Compare incidental vs. non-incidental TC (ITC vs. NITC) regarding demographic, clinical, histological data and 5-year clinical outcomes. Retrospective analysis of 225 papillary TC (PTC) cases that completed a 5-year follow-up. Created 2 groups: ITC (including the incidentalomas) and NITC (cases of palpable or visible nodules or with thyroid compressive complaints). Included 225 PTC (122 were ITC). There were 95 women in ITC and 78 in NITC. ITC patients were significantly older (53.3±14.8 vs 47.2±17.7, p=0.006). Groups had no differences in family history of TC. ITC mean tumour size was smaller (19.1±9.2 vs 28.6±16.2, p<0.01). Tumours >20mm comprised 36.1% of ITC and 58.2% of NITC. We found no differences in tumour multifocality, histological thyroiditis, aggressive PTC subtypes, capsule or lymph-vascular invasion and gross extrathyroidal extension. There were no differences regarding the number of patients submitted to RAI or in RAI activity. pTMN staging showed higher prevalence of T3a and T4 cases (p<0.01), and M1 status (p=0.025) in NITC. There were no differences in the rates of persistence of disease. Logistic regression showed that the diagnostic modality had no impact on the 5-year clinical outcome. ITC patients were older and had smaller tumours. NITC showed no worst histological features or 5-year clinical outcome. Approximately, one third of ITC had diameters >20mm. As even large tumours can be ITC, overdiagnosis can be the most likely cause for the TC increasing incidence.

Abstract PO3-17-11: The Utility of Oncotype DX in Grade 1 Hormone Receptor-Positive Early Breast Cancer: Insights from a Multicentric Real-World Data Study

Abstract Background: The Oncotype Dx (ODX) genomic risk score (RS) has become an essential tool in clinical practice for guiding adjuvant chemotherapy decisions in early-stage hormone receptor-positive (HR+), HER2-negative breast cancer (BC). Since some of the genes evaluated in the genomic RS tests are proliferation-related, the use of the test is less clear in tumors with low proliferation, such as histologic grade 1 tumors or those with a low Ki67-index. In contrast to common understanding, however, ODX RS is determined more strongly by estrogen-related features and only weakly by proliferation markers. Methods: This multicentric real-world data (RWD) study aimed to evaluate the usefulness of (ODX) in patients with grade 1 (G1) HR+, HER2-negative BC. The study population consisted of patients treated between 2009 and 2020 across nine Brazilian cancer centers. Key endpoints included the prevalence of high genomic RS in the histologic grade 1 cohort, recurrence rates based on genomic risk, and invasive disease-free survival (IDFS). Results: A total of 651 patients with HR+, HER2-negative BC who underwent Oncotype Dx testing were evaluated. Among 651 patients evaluated, 128 had HG1 tumors, constituting the focus of this analysis. The majority of patients were aged over 50 years (59.4%), had breast carcinoma of non-special type (75.8%), and Ki67 index lower than 20% (77%). Tumor stage distribution revealed 28.1% T1b, 50% T1c, and 14% T2 cases. Additionally, 74.2% were classified as N0, 9.4% as N1mic, and 16.4% as N1. According to the binary categorization based on Adjuvant! algorithm, 92.2% of patients (n=118) had a low clinical risk. ODx analysis showed that 21.9% had a low RS, 74.2% had an intermediate RS, and only 3.1% had a high RS. Among the few patients with a high genomic RS, only one patient did not receive adjuvant chemotherapy. With a median follow-up of 38.3 months, three patients experienced recurrence, all of whom had an intermediate RS. Among these cases, two patients were younger than 50 years, had low clinical risk, and a genomic RS of 18-24; both had locoregional recurrences. The third patient, aged over 50 years, had high clinical risk, a RS of 12, and had a distant recurrence. The recurrence rates according to Ki67 index were 1.1% for patients with Ki67 index &amp;lt; 20% and 7.1% for those with Ki67 index ≥ 20%. Notably, no recurrences were observed in the high genomic risk group. The estimated 5-year IDFS rate was 96.9% (95% CI 88.2% - 99.2%). Conclusion: In the context of G1 BC and low clinical risk, the utility and cost-effectiveness of ODX may be limited. These findings emphasize the importance of carefully assessing clinical risk when selecting patients for genomic RS tests, thereby optimizing resource utilization. Longer follow-up is planned for this RWD cohort. Citation Format: Renata Colombo Bonadio, Leandro Oliveira, Daniel Batista, Daniela Rosa, Artur Katz, Max Mano, Daniele Assad-Suzuki, Daniel Argolo, Solange Sanches, Rafael Kaliks, Débora Gagliato, Thais Megid, Daniel Musse, Tatiana Correa, Andrea Shimada, Romualdo Barroso-Sousa, Marcelle Cesca, Débora Gaudêncio, Larissa Moura, Julio Araujo, José Bines, Laura Testa. The Utility of Oncotype DX in Grade 1 Hormone Receptor-Positive Early Breast Cancer: Insights from a Multicentric Real-World Data Study [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-17-11.

The Ginsburg–Sands theorem and computability theory

The Ginsburg–Sands theorem from topology states that every infinite topological space has an infinite subspace homeomorphic to exactly one of the following five topologies on ω: indiscrete, discrete, initial segment, final segment, and cofinite. The original proof is nonconstructive, and features an interesting application of Ramsey's theorem for pairs (RT22). We analyze this principle in computability theory and reverse mathematics, using Dorais's formalization of CSC spaces. Among our results are that the Ginsburg–Sands theorem for CSC spaces is equivalent to ACA0, while for Hausdorff spaces it is provable in RCA0. Furthermore, if we enrich a CSC space by adding the closure operator on points, then the Ginsburg–Sands theorem turns out to be equivalent to the chain/antichain principle (CAC). The most surprising case is that of the Ginsburg–Sands theorem restricted to T1 spaces. Here, we show that the principle lies strictly between ACA0 and RT22, yielding arguably the first natural theorem from outside logic to occupy this interval. As part of our analysis of the T1 case we introduce a new class of purely combinatorial principles below ACA0 and not implied by RT22 which form a hierarchy generalizing the stable Ramsey's theorem for pairs (SRT22). We show that one of these, the Σ20 subset principle (Σ20-Subset), has the property that it, together with the cohesive principle (COH), is equivalent over RCA0 to the Ginsburg–Sands theorem for T1 CSC spaces.

Comparison of mismatch repair and immune checkpoint protein profile with histopathological parameters in pancreatic, periampullary/ampullary, and choledochal adenocarcinomas.

Pancreatic, periampullary/ampullary, and choledochal adenocarcinomas are aggressive malignancies with a poor prognosis. Immune checkpoint blockade is a promising treatment option for several tumor types. H long terminal repeat-associating 2 (HHLA2), which is analogous to programmed death-ligand 1 (PD-L1), is a recently discovered member of the B7/cluster of differentiation 28 family and is expressed in many malignancies. To analyze the expression of HHLA2 and its association with the pathologic biomarkers that predict sensitivity to immunotherapy. Ninety-two adenocarcinoma cases located in the pancreas, ampulla, and distal common bile duct were identified. This study assessed 106 pancreaticoduodenectomy and distal/total pancreatectomy samples that were delivered to Ankara City Hospital between 2019 and 2021. Immunohistochemistry was conducted to examine the expression of DNA mismatch repair (MMR), PD-L1, and HHLA2 proteins. Patients with high HHLA2 expression had a higher mean age than those with low expression. Low HHLA2 expression was associated with high perineural invasion. HHLA2 expression was low in pathological stage T3 (pT) 3 cases and high in pathological stage T1, T2, and T4 cases. There was no correlation between HHLA2 expression and the expression of MMR proteins and PD-L1. Evaluation of HHLA2 expression in microsatellite stable and PD-L1-negative tumors may be useful for predicting the response of individuals to immunotherapy and may serve as a novel therapeutic target for immunotherapy in advanced-stage disease.

Awake endoscopic laser surgery for early glottic carcinoma.

The objective of this study was to demonstrate the oncologic efficacy of awake endoscopic laryngeal surgery in the treatment of T1-T2 glottic carcinoma. This is a retrospective study. Seventy-one patients with early glottic carcinoma (T1a- 26, T1b- 18, T2- 27) who underwent awake flexible endoscopic laryngeal surgery under local anesthesia and mild intravenous sedation were included in the study. In 64 cases (90.1%) only endoscopic tumor ablation by Nd:YAG laser (in 32.4% of cases being preceded by diathermy snare excision) was performed, and in 7 T2 cases postoperative radiotherapy was also offered. There were no complications during or after the endoscopic surgery. Ultimate control of disease, including salvage treatment, was obtained in 67 patients (94.4%). Cure without recurrence was achieved in 60 cases (84.5%). Local control without salvage radiotherapy or/and open surgery was achieved in 64 (90.1%) patients. Larynx preservation was obtained in 66 (93.0%) cases. At 5 years from the beginning of endoscopic treatment, 74.6% of the patients were alive and free of disease. The best results were obtained in the T1a group of treated patients, all the patients being free of disease with the preserved larynx. Awake endoscopic laryngeal surgery is a safe and oncologically efficient method of treatment of early glottic carcinoma that can be considered as an alternative to the traditional approach, primarily, for patients with risks/contraindications for radiotherapy, general anesthesia, and transoral microsurgery, and also for the patients who prefer to avoid general anesthesia with its related risks and would rather choose office-based laryngeal surgery.

The High Resolution MASS spectrometry in Personalised Medicine: Retinol-Binding Protein 4 as a Candidate Biomarker Predictor of Progression in Bladder Urothelial Carcinoma

Introduction: Bladder cancer (BC) is the seventh most commonly diagnosed cancer in males. A large proportion of T1 cases and some Ta cases are under-staged and the significant risk of residual tumour after initial TURB of TaT1 lesions has been demonstrated. A second TURB is recommended in T1 tumours because it can increase recurrence-free survival (RFS) providing prognostic information. Non-invasive methods differentiating bladder cancer stages would be essential for diagnosis of under staged cases. Previously we demonstrated that a panel of urinary proteins measured by high resolution mass spectrometry could predict bladder cancer stages namely Ta, T1 and T2 cases. Our aim is to increase the accuracy of the biomarker panel for BC stage differentiation using a more patients, also intending to identify proteins that could be a signature to bladder cancer progression. Methods: Forty-eight urine samples were collected from volun- teers of these groups: 20 patients with bladder cancer stage Ta; 19 patients with BC stage T1 and 9 patients with BC stage T2+ (T2, T3 and T4). Urinary proteome was cleaned and digested using the Filter-Aided Sample Preparation methodology and analysed by liquid chromatography-mass spectrometry. For protein identification and label-free quantification we used MaxQuant, the data was further interrogated with the bioinformatics platform Perseus. Results: A biomarker panel was developed which consists of 87 proteins which were down-regulated between three different urothelial bladder carcinoma stages evaluated. Retinol-binding protein 4 (RBP4) consistently increases from Ta to T1, to T2+ (p &lt;0.001) and in high grade tumours (p = 0.006). Conclusion: Our results showed a proteomic biomarker panel capable to differentiate bladder cancer stages. Besides, retinolbinding protein 4 can be a candidate signature of progression.

Disseminated ependymal dysembryoplastic neuroepithelial tumor: a case report and literature review

We present a rare case of T1- and T2-negative ventricular system tumor. Only FIESTA imaging revealed dissemination with multiple focal lesions of the third ventricle, its bottom and lateral walls, anterior horns of lateral ventricles, cerebellar vermis, cervical and lumbar spinal cord. The patient underwent transcortical endoscopic biopsy of the third ventricle tumor with simultaneous ventriculoperitoneal shunting. DNET was diagnosed, and radiotherapy was subsequently performed. Literature data on this issue were analyzed. To date, disseminated forms of DNET are extremely rare. X-ray features and morphological results allow us to establish the correct diagnosis and determine further treatment strategy.

"Slim-Mesh" Technique for Diastasis Recti Abdominis, Including Obesity-Related Cases.

We operated on a series of mostly obese patients with diastasis recti abdominis using the "Slim-Mesh" technique to repair/reinforce the diastasis and linea alba/recti muscles without plicating and traumatizing them. Additional objectives were to decrease operation time and intra- and postoperative complications. We considered T1 cases diastasis after pregnancy and T2 cases obesity (BMI ≥ 30 mg/kg2); D1, D2, and D3 when the diastasis measured 2-3, 3-5, and ≥ 5 cm, respectively; H0 and H1 without and concomitant umbilical and/or epigastric hernia, respectively. At our Department, between May 2010 and November 2022, 47 patients with diastasis recti were operated on with the "Slim-Mesh" technique to reinforce/repair the traumatized linea alba/recti muscles, without plicating them. This was a prospective (83%)-retrospective study. We studied 23 males and 24 females. Mean age and BMI was 58 years and 29 kg/m2, respectively. Groups D1, D2, and D3 comprised 6, 23 and 18 patients, respectively; groups T1, T2, H0 and H1 comprised 22, 25, 13 and 34 patients, respectively. Mean operation time for all cases was 100 minutes. Mean length of hospital stay was 2.3 days and follow-up time was 5 years. We had 6 late postoperative complications: 3 hernia recurrences and 3 trocar site hernias. Considering the lack of agreement on the best surgery for diastasis recti abdominis repair, in our experience the "Slim-Mesh" technique is a valid, safe and easy-to-reproduce way to save, repair and reinforce linea alba/recti muscles in diastasis recti patients, including the obese population (53%).

Receptor Positive Breast Lesions and Status of Axillary Lymph Node.

Objective This study aimed to examine the axillary pathological condition through the development of an assessment framework for hormone receptor-positive breast cancer subsequent to neoadjuvant chemotherapy (NAC). Furthermore, the primary objective of this study was to examine the association between axillary status and breast tumors that are positive for hormone receptors following neoadjuvant chemotherapy. Methodology The present retrospective investigation encompassed a cohort including 300 individuals who were administered neoadjuvant chemotherapy before receiving surgical intervention. The data collection period for this study was from September 2021 to December 2022. All patients received neoadjuvant chemotherapy, per the guidelines established by the National Comprehensive Cancer Network (NCCN). We divided patients into two distinct groups: a test set of 250 patients and a validity set of 50 patients. Patients with no evidence of lymphoid involvement underwent a biopsy of sentinel lymph nodes (SLNB) and would have undergone axillary dissection if the biopsy results had indicated positive findings. A logistic regression analysis was employed to investigate the variables linked to the presence of residual positive axillary lymph nodes in the test set. Subsequently, a multivariate analysis was conducted on the variables that exhibited a p-value below 0.2 in the univariate study. In addition, a value of 1 was assigned to all risk factors to construct a comprehensive correlation prediction model. Results The participants included in this study had a mean age and body mass index (BMI) of 46.24 ± 9.1 years and 25.8 ± 2.5 kg, respectively. The present investigation examined the presence of pathological axillary metastases in a cohort of 188 patients, which accounted for 62.55% of the total sample, by utilizing core-needle biopsy. Furthermore, the incidence rates of individuals presenting with clinical T1 were reported as 14.6%, while 55.2% cases of T2, 17.8% cases of T3, and 13% cases of T4 tumors were reported, respectively. Of the overall occurrences, the prevailing histological subtype was invasive ductal carcinoma, accounting for 91.4% (222 out of 243) of the cases. Multiple criteria were identified as independent predictors of the presence of residual positive axillary lymph nodes. The factors under consideration encompass lymphovascular invasion (odds ratio= 7.108; 95% breast cancer stage (odd ratio = 5.025; 95%, HER2 negativity (odd ratio= 2.997), low Ki-67 expression (odd ratio = 4.231), and suspected positive axillary lymph nodes before surgical intervention. Conclusion The present study presents a novel prediction model that integrates imaging and pathology data, aiming to assist patients and healthcare practitioners in evaluating the efficacy of NACfor hormone-receptor-positive breast tumors. The model holds particular significance for individuals who exhibit clinical positivity in their lymph nodes (LNs). Consequently, the model has the potential to provide guidance for the management of axillary lymph nodes and prevent unnecessary dissection.

Exploring the Quantum Spectral Curve for AdS3/CFT2

Despite the rich and fruitful history of the integrability approach to string theory on the AdS3 × S3 × T4 background, it has not been possible to extract many concrete predictions from integrability, except in a strict asymptotic regime of large quantum numbers, due to the severity of wrapping effects. The situation changed radically with two independent and identical proposals for the Quantum Spectral Curve (QSC) for this system in a background of pure Ramond-Ramond flux. In other integrable superstring backgrounds there is compelling evidence that this formulation captures all wrapping effects exactly and describes the full planar spectrum. This great success motivates us to study the new proposed QSC and develop methods to extract from it concrete predictions for spectral data. The AdS3 × S3 × T4 case presents a significant novel feature and challenge compared to its higher-dimensional analogues — massless modes. It has been conjectured that these manifest themselves in a new property of this QSC: the non-quadratic nature of the branch-cut singularities of the QSC Q-functions. This feature implies new technical challenges in solving the QSC equations as compared to the well-studied case of N\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$ \\mathcal{N} $$\\end{document} = 4 SYM. In this paper we resolve these difficulties and obtain the first ever predictions for unprotected string excitations in the planar limit with finite quantum numbers and RR flux. We explain how to extract a systematic expansion around the analogue of the weak ’t Hooft coupling limit in N\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$ \\mathcal{N} $$\\end{document} = 4 SYM and also obtain high-precision numerical results. These concrete data and others obtainable from the QSC could help to identify the so-far mysterious dual CFT.

Impact of COVID-19 on gynecological cancer incidence: a large cohort study in Japan.

The influence of the coronavirus disease 2019 (COVID-19) pandemic on the number of newly diagnosed gynecological cancers has not been extensively investigated in Japan. This study determined the impact of COVID-19 on the incidence of gynecological cancer. Using the Japanese Society of Obstetricians and Gynecologic Oncology registry database, the distribution of the number of patients based on clinical staging or tumor-node-metastasis classifications before and during the COVID-19 pandemic was analyzed to compare the trends. The clinical staging classification of cervical cancer in Japan was based on the International Federation of Gynecology and Obstetrics (FIGO) 2008 from 2018 to 2020 and on the FIGO 2018 from 2021. Since FIGO-2018 classified N1 cases as stage IIIC, we focused on T classification without referencing the clinical staging (FIGO staging) of patients with cervical cancer in 2021. The number of patients with endometrial cancer and malignant ovarian tumors of all clinical stages increased uniformly yearly, while that of those with stage III cervical cancer rapidly increased in 2021 owing to the adoption of the revised classification. On comparing cases of cervical cancer in 2020 and 2021, we found that T1 cases decreased and T2 and T3 cases increased in 2021 compared to those in 2020 (p = 0.006). Cervical intraepithelial neoplasia/adenocarcinoma in situ incidence decreased in 2020 compared to that in 2019 but increased again in 2021. The number of patients with cervical cancer decreased in most prefectures in 2020. The incidence of locally advanced cervical cancer increased during the COVID-19 pandemic.

The features of PD-L1 expression in tumor stromal cells, peritumoral microvessels and isolated clusters of tumor cells in breast cancer tissue and their correlation with clinical and morphological characteristics of breast cancer

Objective: to study the features of PD-L1 expression in tumor stromal cells, peritumoral microvessels, and isolated clusters of tumor cells in breast cancer (Bc) tissue and their correlation with the clinical and morphological characteristics of Bc.Material and Methods. The study included 158 patients with newly diagnosed invasive BC. PD-L1 expression was studied by immunohistochemistry. statistical analysis was performed using statistica 12.0 software.Results. PD-L1 expression in peritumoral microvessels occurred in 41.4 and 61.7 % of cases with t1–2 and T3–4 (p=0.020), and in 39.8 and 51.7 % of cases with N0–1 and N2–3 (p=0.008), respectively. In isolated clusters of tumor cells, the marker expression was observed in 28.0 and 52.5 % of cases in nodular and diffuse forms of BC (p=0.005); in 25.9, 39.3 and 66.7 % of cases at stages I–IIb, IIIa–IIIc and IV (p=0.011); in 30.3, 26.2, 40.0 and 52.5 % of cases in T1, T2, T3 and T4 (p=0.040); and in 28.2 and 45.5 % of cases in N0–1 and N2–3 (p=0.030), respectively. Nuclear expression of PD-L1 was also detected in stromal cells, and was observed in 28.8 and 55.0 % of cases with nodular and diffuse forms of BC (p=0.003), in 17.6, 52.5 and 75.0 % of cases in early, locally advanced and metastatic BC (p&lt;0.001), in 21.2, 28.7, 80.0 and 55.0 % of cases in T1, T2, T3 and T4 (p=0.002), in 21.7, 35.3, 51.4 and 55.0 % of cases with N0, N1, N2 and N3 (p=0.005), in 49.0 and 29.0 % of cases with negative and positive status of PR (p=0.014), in 30.3 and 52.8 % of cases with HER2-negative and HER2-positive BC status (p=0.014), respectively.Conclusion. The data indicate the relationship between PD-L1 expression and BC progression. The determination of PD-L1 expression in peritumoral microvessels and isolated tumor cell clusters, as well as nuclear expression of the marker, can be used to clarify the prognosis of the disease.

Subserosal Layer and/or Pancreatic Invasion Based on Anatomical Features as a Novel Prognostic Indicator in Patients with Distal Cholangiocarcinoma.

The American Joint Committee on Cancer (AJCC) 8th edition T-staging system for distal cholangiocarcinoma (DCC) proposes classification according to the depth of invasion (DOI); nevertheless, DOI measurement is complex and irreproducible. This study focused on the fibromuscular layer and evaluated whether the presence or absence of penetrating fibromuscular invasion of DCC contributes to recurrence and prognosis. In total, 55 patients pathologically diagnosed with DCC who underwent surgical resection from 2002 to 2022 were clinicopathologically examined. Subserosal layer and/or pancreatic (SS/Panc) invasion, defined as penetration of the fibromuscular layer and invasion of the subserosal layer or pancreas by the cancer, was assessed with other clinicopathological prognostic factors to investigate recurrence and prognostic factors. According to the AJCC 8th edition, there were 11 T1, 28 T2, and 16 T3 cases, with 44 (80%) cases of SS/Panc invasion. The DOI was not significantly different for both recurrence and prognostic factors. In the multivariate analysis, only SS/Panc was identified as an independent factor for prognosis (hazard ratio: 16.1; 95% confidence interval: 2.1-118.8, p = 0.006). In conclusion, while the determination of DOI in DCC does not accurately reflect recurrence and prognosis, the presence of SS/Panc invasion may contribute to the T-staging system.

Strict versus Liberal Use of Sentinel Node Biopsy in Breast Cancer Surgery: Any Clinical Outcome Differences? A 20-Year Clinical Experience

Introduction: As applied to early breast cancer (BC) patients, sentinel node biopsy (SNB) has undergone major changes over the years, especially concerning the widening of indication criteria or skipping systematic axillary lymph node dissection (ALND) after a positive SN. We aimed to ascertain whether a strict versus a more liberal use of SNB resulted in different clinical outcomes in our clinical experience. Methods: We studied consecutive BC patients undergoing SNB between January 1, 2000, and March 31, 2020. There were 1,587 patients and 1,634 SNB procedures. Cases were divided into two study groups: the “strict” SNB group (unifocal tumors up to 35 mm in which ALND was always performed for a positive SN, amounting to 1,183 SNBs), and the “liberal” SNB group (extended tumor size up to selected T3 cases, as well as multifocal or bilateral disease, and patients with previous contralateral BC, not always followed by ALND after a positive SN, amounting to 451 SNBs). Patients were closely followed up to the end of the study. Results: Clinico-pathological variables were strikingly different between study groups, with the liberal group showing a higher risk profile. Cox regression analysis for disease recurrence did not show significant differences in axillary, lymph node, or locoregional recurrence rates or distant relapse. There were no differences in survival between groups. Conclusion: It seems reasonable to adopt the liberal SNB approach, as the goal of surgical management in early BC patients must be attaining optimal locoregional disease control, no matter the differences in distant metastatic spread rates across different BC risk profiles.

Oncologic effectiveness of open partial vertical laryngectomy in the treatment of early glottic cancer

Introduction. In the last decades, a discernable trend towards more frequent use of endoscopic laser surgery in operative treatment of cancer of the middle part of the larynx is observed. Smaller operative trauma, absence of tracheostomy, short hospitalization time, and better functional outcomes without compromising oncological outcomes are significant reasons for transition to endoscopic methods. However, local recurrence involving anterior commissure develops in every 4th patient. This can explain attempts to return to analysis of possibilities of a surgical alternative – open laryngectomies.Aim. To retrospectively analyze the oncologic effectiveness of open partial vertical laryngectomy in the treatment of early glottic cancer.Materials and methods. Results of treatment of 66 patients aged between 39 and 72 years (mean age 61.4 ± 8.7 years) with cT1–2N0m0 glottic cancer were analyzed. 33 patients had T1 tumors and 33 – T2. Anterior commissure was involved in 14 cases. Surgery was the only mode of treatment in 92.4 % of cases. Oncologic effectiveness was assessed with the following parameters: the rate of local, regional recurrence and kaplan–meyer overall survival.Results. mean follow up was 58.64 ± 28.33 months (range 8–120 months). The rate of local recurrence for the whole cohort, T1 and T2 cases was 4.5; 3.0 and 6.1 %. The difference in local recurrence rate between T1 and T2 cases was statistically insignificant. The anterior commissure involvement did not affect negatively the rate of local recurrence. Regional recurrence was detected in 3 (4.5 %) patients. Larynx was preserved in 63 patients (92.4 %). 5 year overall survival was 86.12 %.Conclusion. Open partial vertical laryngectomy is characterized by low rate of local recurrence and acceptable functional results. The method may be the optimal choice of treatment for certain subgroup of patients with more advanced and invasive tumors.

Factors affecting recurrence and metastasis in conjunctival melanoma.

To evaluate clinical and demographic characteristics and factors affecting recurrence, metastasis, and survival in conjunctival melanoma (CM). The clinical records of 45 patients who were treated for CM between October 1998 and June 2022 were retrospectively evaluated. Age, gender, presence of underlying conjunctival nevus-primary acquired melanosis (PAM), tumor stage according to the 8th edition of the American Joint Committee on Cancer (AJCC) staging system, tumor basal diameter, tumor thickness, lymph node (LN) involvement, metastasis, presence of tumor at the surgical margin, treatment method, need for adjuvant therapy, local tumor control, recurrence, and survival were recorded. Twenty-one (46.7%) patients were female and 24 (53.3%) patients were male. The mean age at diagnosis was 53.2 ± 16.1years. Median follow up time was 12 (1-300) months. Fifteen (33.3%) patients had conjunctival PAM; 2 (4.4%) patients had conjunctival nevus. The tumor stage was T1 in 24 (55.8%), T2 in 13 (30.2%), and T3 in 6 (14.0%) of the cases. The T stage in 2cases could not be determined.For stage T1 and T2 CM, in addition to excisional biopsy (EB) and cryotherapy, alcohol epitheliectomy (AE) was performed in 17 cases (37.8%), superficial sclerectomy (SS) was performed in 7 (15.6%), and amnion membrane transplantation (AMT) due to a large conjunctival defect in 9 (20.0%). Six (14.0%) T3 cases underwent primary exenteration. Positive surgical margins were observed in 23 (51.1%) of the excised tumors at histopathologic examination. Adjuvant topical mitomycin-C (MMC) was used in 7 (30.4%) and strontium-90 episcleral brachytherapy in 4 (17.4%) of the 23 cases with tumor-positive borders. During the follow-up, recurrence was seen in 14 (31.1%) cases. According to Kaplan Meier analysis, the mean time to recurrence development was 90.5 ± 16.1months and the 5-year recurrence free rate was 52.0%. Fourteen of the recurrent cases underwent EB + cryotherapy, 3 underwent AE + SS, and 3 underwent secondary exenteration. Metastasis and LN involvement occurred in 11 (24.4%) and 8 (17.8%) of the cases, respectively. Four (8.9%) cases expired during follow-up. According to Kaplan-Meier analysis, the mean time to metastasis was 106.2 ± 17.3months and the 5-year metastasis free rate was 52.0%. While recurrence was more frequent in CM developing from PAM/nevus, metastasis was more frequent in men and those with LN involvement. Conjunctival melanoma was a malignant tumor with high recurrence and metastasis rates. Precursor nevus/PAM is a risk factor for recurrence, while male gender and regional LN involvement were risk factors for metastasisin this study.

Indications for sentinel lymph node biopsy in node-negative oral cancers.

We aimed to define the indications for sentinel lymph node biopsy (SLNB), the third option for cervical treatment in oral cancer with negative cervical lymph nodes. The greatest depth of invasion (DOI) and long diameter (LD) of the primary site were used as exposures. SLN metastasis was considered the outcome. In three trials conducted between 2009 and 2016, 158 patients were eligible and reassigned to this study group. The scatterplot based on the respective values of DOI and LD would eventually be divided into three sections. In cases of sections T1, T2, and T3, the proportions of SLN metastasis positivity were 21.3%, 35.3%, and 51.2%, respectively. In certain cases of T1 with 2 mm < DOI ≤ 5 mm and 8 mm < LD ≤ 20 mm, the proportion of SLN metastasis positivity was 40.9%. SLNB-navigated or assisted neck dissection can be added as an effective procedure for N0 neck control.