Presence Of Distant Metastases Research Articles

Concurrent hyperthermic intraperitoneal chemotherapy and intraoperative radiotherapy with cytoreductive surgery in patients with rectal cancer with peritoneal carcinomatosis.

e15571 Background: Rectal cancer (RC) is often associated with peritoneal carcinomatosis (PC). Hyperthermic intraperitoneal chemotherapy (HIPEC) and intraoperative radiotherapy (IORT) have been shows to reduce recurrence and effectively treat PC across several cancers. However, little evidence is available regarding the concurrent use of HIPEC and IORT alongside cytoreductive surgery (CRS) in the literature. Methods: We retrospectively reviewed the medical records of RC patients with PC who received HIPEC plus IORT during CRS at the King Faisal Specialist Hospital and Research Centre. Demographic data, PC index (PCI), completeness of cytoreduction (CC), and tumor staging were collected. Overall survival (OS) was calculated from the time of surgery until death or last follow-up. Recurrence-free survival (RFS) was calculated from the time of surgery until recurrence or last follow-up. Unadjusted hazard ratios (HR) were used to determine the impact of parameters on OS or RFS. Results: 17 patients were included in our analysis. Basic demographic data can be found in Table 1. The most common operation performed was rectosigmoid resection in 7 (41.2%) patients, followed by low anterior resection in 6 (35.3%). The pT stage was T0 in 1 (5.9%), T4a in 7 (41.2%), and T4b in 9 (52.9%). The pN stage was N0 in 11 (64.7%), N1a in 1 (5.9%), N1b in 2 (11.8%), N1c in 2 (11.8%), and N2b in 1 (5.9%). There was positive resection margin in 2 patients. The PCI was ≤6 in 15 (88.2%), and the CC score was 0-1 in all patients. No patients had intraoperative complications. 12 (70.6%) received mitomycin C, 4 (23.5%) received cisplatin and mitomycin C, and one patient received a reduced dose of mitomycin C due to old age. 2 (11.8%) patients received two doses of IORT. 11 (64.7%) patients had postoperative complications, of which all were Clavein-Dindo grades 1-3b. Recurrence occurred in 11 (64.7%). The median OS was not reached, and the median RFS was 12 months. There were no parameters associated with OS. Male gender (HR: 7.7, 95% CI: 1.4-57.3), pM1 (HR: 4.5, 95% CI; 1.2-18.1), and perineural invasion (HR: 6.5, 95% CI: 1.2-49.3) were associated with poor RFS in univariate analysis. Conclusions: Incorporating HIPEC and IORT into CRS may be an effective treatment strategy for RC patients. Presence of distant metastasis and perineural invasion can be predictors of rapid recurrence. [Table: see text]

Possibilities of long-term atezolizumab immunotherapy in patients with metastatic urothelial cancer.

e14628 Background: Results from various studies have indicated that atezolizumab can be an effective and well-tolerated treatment option for patients with advanced and metastatic urothelial cancer. However, the landscape of oncological practices in Uzbekistan reflects a scarcity of experience and data concerning the utilization of atezolizumab in the treatment of patients afflicted with urothelial cancer. This research endeavors to bridge this gap by contributing. Methods: In our retrospective study, a total of 44 patients were selected, with a mean age of 64.5±7.6 years, diagnosed with stage IV urothelial cancer and the presence of distant metastases in the lungs, bones, and liver. There were 28 (63.6%) males and 16 (36.4%) females. Group 1 included 18 (40.9%) patients with elevated PD-L1 levels SP142 – IC 2/3, receiving atezolizumab at 1200 mg intravenously (IV) on day 1 of each 21-day cycle + cisplatin at a dose of 70 mg/m2 body surface area (BSA), IV, on day 1 of each cycle, and gemcitabine at a dose of 1000 mg/m2 BSA, IV, on days 1 and 8 of each cycle. Group 2 included 26 (59.1%) patients receiving standard chemotherapy (cisplatin + gemcitabine) in the same regimens. Immunohistochemical analysis was performed using the Ventana Bench Mark Ultra automated stainer with Ventana PD-L1 SP142 monoclonal antibodies. Results: The research was conducted from September 2019 to May 2023, and the administered treatment was the first line for these patients. Treatment was administered until disease progression was registered or until the development of unacceptable toxicity. Grade I toxicity was not observed in both groups. Grade II toxicity in Group 1 was noted in 3 (16.7%), and in Group 2 - in 4 (15.4%). Grade III toxicity was identified in 9 patients (50.0%) in Group 1 and 14 patients (53.8%) in Group 2. Grade IV toxicity was encountered in 6 patients (33.3%) in Group 1 and 8 patients (30.8%) in Group 2. Hematological toxicity, regardless of atezolizumab use, predominated among the III and IV degrees of toxicity. The median overall survival in Group 1 was 14.8 months (95% CI: 12.8-16.2), while in Group 2, it was 11.9 months (95% CI: 9.3-13.5). Progression-free survival in Group 1 was 6.8 months (95% CI: 5.1-7.4), and in Group 2, it was 4.3 months (95% CI: 3.8-5.7). The objective response rate in Group 1 was 44.5%, and in Group 2, it was 38.5%. Conclusions: Atezolizumab, used in combination with standard platinum-based chemotherapy in the first line, improves treatment outcomes for metastatic urothelial cancer by increasing overall survival and progression-free survival without causing an increase in the toxicity of the administered therapy.

Radioactive iodine refractoriness in Middle Eastern differentiated thyroid cancer: clinical outcome and risk factor analysis.

Radioactive iodine refractory differentiated thyroid cancer (RAIR-DTC) has received increasing attention due to its poor prognosis. However, outcomes may vary among patients with RAIR-DTC. The role of clinico-pathological and molecular prognostic factors in survival remains controversial, resulting in difficulty in selecting patients for new targeted therapies. We assessed mortality rate and DTC-specific survival in Middle Eastern RAIR-DTC to identify prognostic factors associated with survival. This single center, retrospective study enrolled 268 patients with RAIR-DTC. Mortality rate and DTC-specific survival were analyzed to identify prognostic factors related to survival. Univariate and multivariate analysis were performed using Cox proportional hazards model. Of the 268 cases of RAIR-DTC, 40.3% (108/268) had absent 131I uptake (either on diagnostic or post-therapy whole body scan), 15.3% (41/268) had progressive disease (PD) despite 131I, 7.5% (20/268) had persistent disease despite cumulative activity of I131 of >600 mCi and 36.9% (n=99/268) developed distant metastasis. On multivariate analysis, age (more than 45 years), presence of metastatic disease and tumors harboring telomerase reverse transcriptase (TERT) promoter mutations were independent prognostic factors for poor DTC-specific survival. Subjects were divided into 3 groups according to the number of risk factors; low risk (no risk factors); intermediate (≤ 2 risk factors); and high risk (all the 3 risk factors). Ten-year DTC-specific survival rates in low, intermediate and high-risk groups were 100.0%, 92.9% and 53.6%, respectively. The contribution of age greater than 45 years to RAIR-DTC mortality is impactful. Older age, presence of distant metastasis and TERT mutations could be used as early predictors of RAIR-DTC cases. The identification of prognostic factors for poor survival in RAIR-DTC may improve the selection of patients for more personalized surveillance and therapeutic modalities.

Relationship between pathohistological characteristics of the tumor and distant metastasis of differentiated thyroid cancer

Papillary thyroid cancer has the most favorable prognosis for patients. According to the recommendations of the National Comprehensive Cancer Network (NCCN), organ‑sparing surgery can be performed for such patients without radioactive iodine therapy (RIT). However, some factors, for example, vascular invasion, multifocality, the presence of regional metastases, etc. increase stratification risks for the patient and give the reason to perform more voluminous surgical interventions and conduct RIT. With differentiated thyroid cancer (DTC), the 5‑year and 10‑year overall survival rates reach 100% and 96%, respectively.
 Objective — to investigate the relationship between the pathohistological characteristics of the DTC tumor and distant metastasis.
 Materials and methods. The study involved 522 patients aged 4 to 79 years (the mean age 40.2±0.6 years) after previous thyroid cancer surgery and RIT. Patients were divided into two groups depending on the presence of distant metastases: 28 (5.4%) with distant metastases and 494 (94.6%) patients without distant metastases.
 Results. Using the data of pathohistological findings, both groups were compared according to the following criteria: pathomorphological DTC subtype, vascular invasion, other extraordinary invasion, multifocality, the size of the primary tumor, the size of the largest focus and the total size of foci for multifocal cancers, the number and maximum size of metastases in the central and lateral lymphatic collectors of the neck.
 Conclusions. No significant relationship has been found between the pathomorphological subtype of differentiated thyroid cancer, the presence of vascular and extra‑organ invasion, and the presence of distant metastases, but a relationship was found with multifocality. In the group of patients with distant metastases, a larger size of the primary focus, and a larger size and number of regional metastases were determined.

Stool Glycoproteomics Signatures of Pre-Cancerous Lesions and Colorectal Cancer.

Colorectal cancer (CRC) screening relies primarily on stool analysis to identify occult blood. However, its sensitivity for detecting precancerous lesions is limited, requiring the development of new tools to improve CRC screening. Carcinogenesis involves significant alterations in mucosal epithelium glycocalyx that decisively contribute to disease progression. Building on this knowledge, we examined patient series comprehending premalignant lesions, colorectal tumors, and healthy controls for the T-antigen-a short-chain O-glycosylation of proteins considered a surrogate marker of malignancy in multiple solid cancers. We found the T-antigen in the secretions of dysplastic lesions as well as in cancer. In CRC, T-antigen expression was associated with the presence of distant metastases. In parallel, we analyzed a broad number of stools from individuals who underwent colonoscopy, which showed high T expressions in high-grade dysplasia and carcinomas. Employing mass spectrometry-based lectin-affinity enrichment, we identified a total of 262 proteins, 67% of which potentially exhibited altered glycosylation patterns associated with cancer and advanced pre-cancerous lesions. Also, we found that the stool (glyco)proteome of pre-cancerous lesions is enriched for protein species involved in key biological processes linked to humoral and innate immune responses. This study offers a thorough analysis of the stool glycoproteome, laying the groundwork for harnessing glycosylation alterations to improve non-invasive cancer detection.

P4HA2 involved in SLUG-associated EMT predicts poor prognosis of patients with KRAS-positive colorectal cancer.

This study aimed to examine the immunohistochemical expression of epithelial-mesenchymal transition biomarkers: P4HA2 and SLUG in colorectal carcinoma (CRC) specimens, then to assess their relation to clinicopathological features including KRAS mutations and patients' survival, and finally to study the correlation between them in CRC. The result of this study showed that SLUG and P4HA2 were significantly higher in association with adverse prognostic factors: presence of lympho-vascular invasion, perineural invasion, higher tumor budding, tumor stage, presence of lymph node metastasis, and presence of distant metastasis. CRC specimens with KRAS mutation were associated with significant higher SLUG and P4HA2 expression. High expression of both SLUG and P4HA2 was significantly unfavorable prognostic indicator as regards overall survival (OS) and disease-free survival (DFS). In KRAS mutated cases, high P4HA2 expression was the only significant poor prognostic indicator as regarding DFS. In conclusions, our data highlight that both SLUG and P4HA2 expression may serve as potentially important poor prognostic biomarkers in CRC and targeting these molecules may be providing a novel therapeutic strategy. In KRAS mutation group, high P4HA2 expression is the only independent prognostic factor for tumor recurrence, so it can be suggested to be a novel target for therapy.

Abstract 6884: Evaluating tumor-infiltrating immune cells helps predicting prognosis in biliary tract cancer

Abstract Background: The tumor microenvironment (TME) is composed of not only cancer cells but also an extracellular matrix and many types of non-cancerous cells, including fibroblasts and immune cells. In recent years, infiltrating immune cells in TME are known as a predictor of chemotherapy and immunotherapy effectiveness. The purpose of this study is to evaluate infiltrations of lymphocytes and macrophages in biliary tract cancers (BTCs). Methods: Clinical data and tissues were obtained from 130 patients who underwent surgical treatment for BTCs (intrahepatic, perihilar, and distal bile duct cancer, gallbladder cancer, and ampullary cancer) at our institution between 2001 and 2017.The immunohistochemical evaluation was performed to evaluate the number of CD8+ T cells, CD4+ T cells and FOXP3+ T cells and CD68+ Macrophages around the tumor cells. We defined Immunoscore based on the status of infiltrating immune cells. With CD8-high, CD4-high, and FOXP3-high TILs and CD68-low TAMs as one factor, the number of factors was counted in each case, and Immunoscore was assigned a score of 5 stages, from 0 to 4. It was high for the score of 3-4 and low for the score of 0-2. Also, to evaluate the correlation with TME and systemic inflammatory reaction, we examined blood inflammatory biomarker from peripheral blood samples. Results: A total of 59 cases had high Immunoscore and 71 cases had low Immunoscore. Patients with high Immunoscore showed significantly superior overall survival (OS) and recurrence free survival (RFS) than those with low Immunoscore (median OS 60.8 vs. 26.4 months, p = 0.001; median RFS not reached vs. 17.2 months, p < 0.001). For OS, low Immunoscore, positive lymph node metastasis, presence of distant metastasis, and high serum CA19-9 level were independent poor prognostic factors (hazards ratio 2.05, 3.48, 1.7, and 2.05; p = 0.01, p = 0.005, p = 0.05, and p = 0.01, respectively). For RFS, low Immunoscore, T classification of pT3-4, and presence of distant metastasis were independent poor prognostic factors with hazards ratio of 2.41 (p = 0.001), 2.16 (p = 0.005), and 3.58 (p = 0.005), respectively. Patients with high preoperative Neutrophil-to-lymphocyte ratio (NLR) had a significantly lower average number of CD8+ T cells as compared to patients with low NLR (p = 0.02). Preoperative NLR was associated with infiltrating CD8+ T cells in TME. Conclusions: High Immunoscore group had significantly longer OS and RFS and was an independent good prognostic factor. Also, infiltrating CD8+ T cells in TME correlated preoperative NLR. Our findings indicated that in biliary tract cancer, the evaluation of infiltrating immune cells in TME was useful to predict patient prognosis, and preoperative NLR may predict the tumor infiltrating CD8+ T cells. Citation Format: Kousuke Hatta, Ryota Tanaka, Kenjiro Kimura, Shinpei Eguchi, Go Ohira, Hiroji Shinkawa, Kohei Nishio, Masahiko Kinoshita, Shigeaki Kurihara, Shuhei Kushiyama, Takahito Kawaguchi, Naoki Tani, Koichi Nakanishi, Mizuki Yoshida, Takeaki Ishizawa. Evaluating tumor-infiltrating immune cells helps predicting prognosis in biliary tract cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6884.

Abstract 6273: GGCT expression is a useful marker for the diagnosis of follicular thyroid carcinoma

Abstract Background: Follicular thyroid carcinoma (FTC) and follicular adenoma (FA) have similar histological findings. FTC is distinct from FA based on the presence of capsular or vascular invasion in the tissues, but it is difficult to confirm the diagnosis in some cases. In this study, we aimed to establish useful molecular maker for differential diagnosis between FTC and FA. Methods: This study included FTC (n = 32), FA (n = 64), and follicular tumors of uncertain malignant potential (FT-UMP, n = 5). Invasive front tissue and tumor center tissue from 3 cases of FTC were collected using a laser microdissection system; RNA was extracted, followed by microarray analysis to examine molecules that were commonly highly expressed in the invasive front. Subsequently, immunohistochemical staining of gamma-glutamyl cyclotransferase (GGCT) was performed. For assessment of GGCT expression, the intensity of the nuclear staining was stratified using a four-tiered scale (0 to 3) and percentage of positive cells (0-100%) in the hotspot. Multiplying intensity score and percent of positive cells, an expression score ranging from 0 to 300 was calculated. The Ki-67 labeling index was examined in 20 cases of FTC, 25 cases of FA, and 4 cases of FT-UMP from the same cohort. We counted at least 2,000 tumor cells in the hot spot for the assessment of Ki-67 labeling index. Results: Microarray analysis revealed GGCT exhibited high expression levels at the invasive front of FTC. In immunohistochemical assessment, GGCT expression scores were significantly higher in FTC than in FA (118.5 ± 51.4 vs. 57.3 ± 34.7, p < 0.0001). The median Ki-67 labeling index were 3.9% (range 0.2 - 16.1) for FTC and 2.4% (range 0.3 - 7.0) for FA. FTC showed a higher Ki-67 index than FA (Wilcoxon rank sum test, p = 0.0444). With GGCT expression score, applying a cutoff value of 101.1, the distinction between FTC and FA resulted in a sensitivity of 68.8% and a specificity of 87.5% (AUC: 0.832). With Ki-67 labeling index, applying a cutoff value of 4.0%, the distinction between FTC and FA resulted in a sensitivity of 50.0% and a specificity of 80.0% (AUC: 0.677). The GGCT expression score was positively related with the Ki-67 labeling index in the FTC cases. (Spearman's ρ = 0.5293, p = 0.0164). There were no significant associations between GGCT expression scores and clinicopathological parameters, including age, gender, tumor diameter, pT stage, pN stage, pattern of capsular invasion, number of foci of vascular invasion, and the presence of distant metastasis. Conclusions: GGCT is a potential marker for differentiating FTC from FA. The GGCT expression of FTC may contribute to estimating the invasive activity and proliferative activity. Citation Format: Toshiyuki Mitsuhashi, Sachiko Ogasawara, Masamichi Nakayama, Reiichiro Kondo, Jun Akiba, Kenta Murotani, Takeharu Ono, Fumihiko Sato, Hirohito Umeno, Hirohisa Yano. GGCT expression is a useful marker for the diagnosis of follicular thyroid carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6273.

Sarcomatoid renal pelvis carcinoma: Experience of treatment at a single-institution

ObjectivesSarcomatoid renal pelvis carcinoma (SRPC) is a rare variant of RPC. We aimed to summarize the clinicopathological features and prognostic factors of SRPC. MethodsIn this retrospective study, we collected data from 24 patients with SRPC who were treated at the Department of Urology, Affiliated Hospital of Qingdao University between 2008 and 2021. The clinicopathological features of the patients were obtained from their medical records to evaluate the diagnosis, prognostic factors, and response to systemic therapy. ResultsImmunohistochemical staining revealed that cytokeratin was expressed in 19 patients with SRPC, while vimentin was expressed in all patients. Computer tomography showed these tumors as low-density (n = 12) or mixed-density masses, with or without necrotic areas (n = 12). All patients showed different degrees of enhancement on computed tomography. Lymph node metastasis was present in 6 patients and distant metastasis in 5. The median survival of all patients was 28 months. Patients without metastasis had a median survival of 46 months compared with 18 months in those with metastasis (P < 0.05). Necrosis had no significant influence on prognosis (P > 0.05). The median survival of patients with and without hydronephrosis was 18 and 104 months (P < 0.05). Among patients without metastasis, those without hydronephrosis survived longer than those with hydronephrosis (104 vs 18 months, P < 0.05), and necrosis had no effect on prognosis. In patients with metastasis, necrosis and hydronephrosis had no effect on prognosis (P > 0.05). ConclusionThe prognosis of SRPC is poor, and the clinical stage, particularly the presence of distant metastasis, has a significant impact on prognosis.

Risk factor analysis and nomogram construction in patients with distant metastatic prostate cancer at different PSA levels: a study based on the SEER database.

Prostate cancer (PCa) is the most common malignant tumor in the male genitourinary system. Once PCa has metastasized, it is very difficult to cure. The purpose of this study was to investigate the prognostic risk factor analysis of patients with different prostate-specific antigen (PSA) levels in distant metastatic PCa. At the same time, we construct effective models for predicting the survival rate of prostate cancer patients. Data on prostate cancer patients with the presence of distant metastases were obtained from the Surveillance, Epidemiology, and End Results (SEER) database. PCa patients with distant metastases were categorized into two groups based on PSA levels, one with PSA <20 ng/mL and the other with PSA ≥20 ng/mL. Univariate and multivariate COX regression analyses were used to identify independent factors affecting the prognosis of the patients. A nomogram was constructed using the independent prognostic factors, and the results were evaluated using calibration curves, timeROC curves, and Kaplan-Meier curves. In the PSA <20 ng/mL group, there were a total of 1,832 patients. COX regression analysis showed that age, marital status, N stage, grade, Gleason score, and medical household income inflation were independent prognostic factors for overall survival (OS) in patients. In addition, we found that age, marital status, N stage, bone metastasis, grade, and Gleason score were independent prognostic factors for cancer-specific survival (CSS) in patients. In the PSA ≥20 ng/mL group, there were a total of 5,314 patients. It was found that age, ethnicity, marital status, bone metastasis, first malignant primary indicator, grade, Gleason score, and medical household income inflation were patients' independent prognostic factors for OS. For CSS, we found that age, ethnicity, marital status, T stage, radiotherapy, bone metastasis, Gleason score, and Median household income inflation were independent prognostic factors. Constructing a nomogram can accurately predict the prognosis of this group of patients. We found different independent prognostic factors for different PSA levels in patients with distant metastatic PCa. A new nomogram was constructed to predict OS and CSS in patients, which helps in clinical-assisted decision-making.

Precision Medicine for Nasopharyngeal Cancer-A Review of Current Prognostic Strategies.

Nasopharyngeal carcinoma (NPC) is an Epstein-Barr virus (EBV) driven malignancy arising from the nasopharyngeal epithelium. Current treatment strategies depend on the clinical stage of the disease, including the extent of the primary tumour, the extent of nodal disease, and the presence of distant metastasis. With the close association of EBV infection with NPC development, EBV biomarkers have shown promise in predicting treatment outcomes. Among the omic technologies, RNA and miRNA signatures have been widely studied, showing promising results in the research setting to predict treatment response. The transformation of radiology images into measurable features has facilitated the use of radiomics to generate predictive models for better prognostication and treatment selection. Nonetheless, much of this work remains in the research realm, and challenges remain in clinical implementation.

Undifferentiated sarcomatoid carcinoma of the pancreas-a single-institution experience with 23 cases

BackgroundThe clinical course and surgical outcomes of undifferentiated sarcomatoid carcinoma of the pancreas (USCP) remain poorly characterized owing to its rarity. This study aimed to describe the histology, clinicopathologic features, perioperative outcomes, and overall survival (OS) of 23 resected USCP patients.MethodsWe retrospectively described the histology, clinicopathologic features, perioperative outcomes and OS of patients who underwent pancreatectomy with a final diagnosis of USCP in a single institution.ResultsA total of 23 patients were included in this study. Twelve patients were male, the median age at diagnosis was 61.5 ± 13.0 years (range: 35–89). Patients with USCP had no specific symptoms and characteristic imaging findings. The R0 resection was achieved in 21 cases. The En bloc resection and reconstruction of mesenteric–portal axis was undertaken in 9 patients. There were no deaths attributed to perioperative complications in this study. The intraoperative tumor-draining lymph nodes (TDLNs) dissection was undergone in 14 patients. The 1-, 3- and 5-year survival rates were 43.5%, 4.8% and 4.8% in the whole study, the median survival was 9.0 months. Only 1 patient had survived more than 5 years and was still alive at last follow-up. The presence of distant metastasis (p = 0.004) and the presence of pathologically confirmed mesenteric–portal axis invasion (p = 0.007) was independently associated with poor OS.ConclusionsUSCP was a rare subgroup of pancreatic malignancies with a bleak prognosis. To make a diagnose of USCP by imaging was quite difficult because of the absence of specific manifestations. Accurate diagnosis depended on pathological biopsy, and the IHC profile of USCP was mainly characterized by co-expression of epithelial and mesenchymal markers. A large proportion of patients have an early demise, especially for patients with distant metastasis and pathologically confirmed mesenteric–portal axis invasion. Long-term survival after radical resection of USCPs remains rare.

A Study of Ki-67 Immunostaining in Prostate Carcinomas and Its Correlation with Gleason's Score and Prognosis: An Experience at a Tertiary Centre in the Himalayan Foothills.

Prostate cancer is a significant cause of cancer-related mortality among men worldwide, necessitating the exploration of prognostic biomarkers to aid in accurate risk assessment and treatment decision-making. This cross-sectional study aimed to comprehensively evaluate the role of Ki-67 as a prognostic marker in prostate cancer by examining its association with clinicopathological parameters. A total of 102 archived cases of prostate core biopsy specimens, histopathologically reported as prostate carcinoma, were included in this study. Histopathological grading was conducted using Gleason's scoring and grading system based on morphology. The statistical software "R" was utilized for data analysis. Kruskal-Wallis test and Fisher's exact test were employed to analyze the association between Ki-67 expression and clinicopathological parameters. The study revealed significant correlations between Ki-67 expression and various clinicopathological parameters in prostate cancer cases. High Ki-67 expression levels were associated with higher Gleason scores, increased incidence of perineural invasion, advanced T stages, lymph node metastasis, presence of distant metastasis, and higher prognostic stage groups. The findings of this cross-sectional study support the potential of Ki-67 as a prognostic marker in prostate cancer. The significant associations observed between Ki-67 expression and clinicopathological parameters indicate its usefulness in risk stratification and treatment decision-making. The incorporation of histopathological grading, including Gleason scoring, and analysis of perineural invasion strengthens the validity of the study. Ki-67, in combination with morphological assessments, provides valuable prognostic information for prostate cancer patients.

A retrospective Italian Society of Veterinary Oncology (SIONCOV) study of 56 cats with appendicular osteosarcoma.

Osteosarcoma is the most common malignant primary bone cancer, but it is infrequently reported in cats. Feline appendicular osteosarcoma typically exhibits good prognosis when treated with surgery alone. A retrospective multi-institutional study was conducted to identify possible prognostic factors. Cats diagnosed with appendicular osteosarcoma were included if initial staging and follow-up information were available. Data including signalment, tumour characteristics, treatment modalities, and survival outcomes were collected and analysed. Fifty-six cats were included; the femur was the most frequently affected bone. Eight cats had distant metastasis at admission and an additional 9 developed metastatic disease during follow-up, resulting in an overall metastatic rate of 30%. Forty-nine (87.5%) cats underwent surgery, and 4 also received adjuvant chemotherapy. Among operated cats, median time to local progression (TTLP), time to distant progression and tumour-specific survival (TSS) were not reached. One- and 2-year survival rates were 66% and 55%, respectively. Seven (12.5%) cats received no treatment; 1- and 2-year survival rates were 25% and 0%, respectively. Operated cats had significantly longer TTLP (P < .001) and TSS (P = .001) compared with non-operated cats. Among operated cats, young age negatively impacted local tumour progression, while the presence of distant metastasis at diagnosis was associated with a higher risk of tumour-related death. This study reaffirms the good prognosis for cats with appendicular osteosarcoma undergoing surgery, but sheds light on some additional factors to consider. Accurate initial staging is recommended, as the metastatic rate may exceed many previous estimations. Surgery substantially extends survival time, whereas the role of chemotherapy remains uncertain.

Abstract B012: TP53 missense mutations and keratin 17 are negative prognostic biomarkers in pancreatic ductal adenocarcinoma

Abstract Background: Cancer patients with similar clinical and pathologic characteristics may have different responses to treatments and survival, which may be attributable to distinct molecular properties of their tumors. In pancreatic ductal adenocarcinomas (PDACs), there is a pressing need to identify prognostic biomarkers that could help us to predict disease progression and patient survival. Our group previously reported that keratin17 (K17) expression is a hallmark of PDACs of patients with the shortest patient survival. Furthermore, there is some evidence suggesting that missense mutations in TP53 are associated with worse survival in patients with PDAC. To date, however, no studies have addressed the differential prognostic value of molecular characterization of TP53 coupled with K17 expression for predicting survival in patients with PDAC. Objective and methods: To fill this gap, we assessed the effect of different TP53 mutations and K17 expression on patient survival, using a clinically annotated cohort of 128 patients containing molecular profiling on patient tumors. K17 Immunohistochemistry (IHC) staining on patient’s formalin-fixed, paraffin-embedded (FFPE) tissue blocks were performed to assess the expression of this marker in tumor cells. K17 IHC scoring was conducted based on a subjective assessment of the overall proportion of stained cells relative to the overall number of tumor cells present in a single representative section from each case. Kaplan-Meier and Cox proportional hazards regression models were analyzed to determine survival differences of patients with PDACs harboring different TP53 mutations and levels of K17 IHC expression, adjusting for patient demographics (age at diagnosis, sex, race/ethnicity) and tumor characteristics (presence of distant metastasis at diagnosis). Results: Tumors were classified as high for K17 when ≥90% of tumor cells showed strong staining. High-K17 cases (n=16;12.50%) had shorter survival compared with low-K17 cases (n=112; 87.50%) (26.80 vs. 16.77 months; P=0.035). The majority of cases harbored missense mutations in TP53 (42.19%), while about one-third harbored truncating TP53 (27.34%) mutations. We found that PDACs with missense TP53 mutations and high K17 were associated with worse patient survival compared to tumors with missense TP53 and low K17 expression (HR=5.27; 95% CI, 1.76-15.82; P=0.003). Similarly, compared with patients with wild-type TP53 and low K17, patients with both missense TP53 mutations and high K17 had significantly worse survival (HR=3.51, 95% CI, 1.45-8.51; P=0.005). Conclusions: Our findings suggest that molecular characterization of specific TP53 mutations coupled with K17 IHC staining may help to determine differences in patient prognosis and identify subgroups with worse patient survival, therefore, potentially guiding future clinical management of patients. Citation Format: Carlos Mauricio Mejia Arbelaez, Gabriella Baraks, Lyanne Oblein, Michael Horowitz, Lynn Matrisian, Kenneth Shroyer, Luisa Fernanda Escobar-Hoyos. TP53 missense mutations and keratin 17 are negative prognostic biomarkers in pancreatic ductal adenocarcinoma [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Pancreatic Cancer; 2023 Sep 27-30; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(2 Suppl):Abstract nr B012.

Pelvic Exenteration for Recurrent Vulvar Cancer: A Retrospective Study.

Pelvic exenteration (PE) is one of the most radical surgical approaches. In earlier times, PE was associated with high morbidity and mortality. Nowadays, due to improved selection of suitable patients, perioperative settings, and postoperative care, patients' outcomes have been optimized. To investigate patients' outcomes and identify possible influencing clinical and histopathological factors, we analysed 17 patients with recurrent vulvar cancer who underwent PE in our department between 2007 and 2022. The median age was 64.9 years, with a difference of 40 years between the youngest and the oldest patient (41 vs. 81 years). The mean overall survival time was 55.7 months; the longest survival time reached up to 164 months. The achievement of complete cytoreduction (p = 0.02), the indication for surgery (curative vs. palliative), and the presence of distant metastases (both p = 0.01) showed a significant impact on overall survival. The presence of lymphatic metastases (p = 0.11) seems to have an influence on overall survival (OS) time. Major complications appeared in 35% of the patients. Our results support the existing data for PE in cases of recurrent vulvar cancer; for a group of selected patients, PE is a treatment option with good overall survival times and acceptable morbidity.

Comparison of aggressiveness in central versus peripheral T1a clear-cell renal cell carcinoma

PurposeThis study aimed to estimate the difference between peripheral and central small renal lesions in terms of their oncologic potential. MethodsCross-sectional retrospective analysis of patients with small renal masses (T1a) who underwent surgical treatment between January 2008 and July 2019 at the affiliated hospital. Only patients with ccRCC pathology were included. Cases were divided into 2 groups depending on tumor location (central or peripheral) based on the R.E.N.A.L and local nephrometry scoring. Presence of nodal involvement, distant metastases, ISUP grade and endophytic growth were defined as aggressiveness predictors. Statistical analyses was performed using a standard statistical software (IBM SPPS Statistics Ver. 22), with P < 0.05 considered statistically significant. Associations between tumor location and Fuhrman grade, exo-/endophytic growth, TNM classification, and type of operation were tested using the Pearson χ² test and 1-way ANOVA test. ResultsPatients with centrally located tumors had a higher incidence of clinical and pathological lymph node involvement (P = 0.02, χ2 = 5.1). Patients in both groups had an equal number of distant metastases at the time of diagnosis (P = 0.3, χ2 = 0.8). The operation time was significantly longer in patients with central lesions, which obviously showed higher tumor complexity in this group (P < 0.005). Pathological evaluation revealed differences between ISUP grades in both groups (P < 0.005, χ2 = 29.9). Central masses were characterized by higher aggressiveness, indicating a worse prognosis. Furthermore, the cases in the first group were more often endophytic (P = 0.03, χ2 = 0.9). Nevertheless, this did not affect the surgical strategy in most cases with a tendency toward partial nephrectomy. Eventually, organ-sparing treatment was preferable in both groups (P = 0.13, χ2 = 2.29). ConclusionCentrally located kidney cancer has showed in present study a higher incidence of high ISUP grade, regional nodal involvement and endophytic growth type. Endophytic growth type was associated with worse ISUP grading. Distribution of ISUP grade was not age depended, thus showing no difference by this criterion, when comparing different age groups. Higher ISUP grade was strongly associated with presence of distant metastases in T1a kidney tumors. Further analysis is needed to investigate aggressiveness of centrally located T1a RCC, as it may influence current conservative management options.

Analysis of clinicopathological features and prognosis of sporadic synchronous multiple primary colorectal cancers

Analysis of clinicopathological features and prognosis of sporadic synchronous multiple primary colorectal cancers

Immunohistochemical Expression of Immune Checkpoints; CTLA-4, LAG3, and TIM-3 in Cancer Cells and Tumor-infiltrating Lymphocytes (TILs) in Colorectal Carcinoma.

Colorectal cancer is considered the third most prevalent cancer in both sexes. Immune checkpoint receptors that regulate T-cell response, stimulation, and development include lymphocyte activating gene 3 (LAG-3), cytotoxic T lymphocyte-associated antigen-4 (CTLA-4), and T-cell immunoglobulin and mucin domain 3 (Tim-3). In addition, they are crucial for the advancement of cancer and tumor immune escape. This work's aim was to assess the immunohistochemistry expression of Tim-3, CTLA-4, and LAG-3 in cancer cells and tumor-infiltrating lymphocytes (TILs) in colorectal cancer (CRC) and the correlation between these markers and clinicopathological variables and survival data. This study involved 206 CRC specimens processed for CTLA-4, LAG3, and TIM-3 immunohistochemistry and correlated with the clinicopathological and survival parameters of the patients. High CTLA-4 epithelial expression was highly related to the old age group, large tumor size, low tumor-stroma ratio (TSR), high grade, advanced stage, the presence of distant metastasis (DM), perineural invasion (PNI), necrosis, lymphovascular invasion (LVI), relapse, mortality, overall survival (OS), and disease-free survival (DFS), while negative CTLA-4 TILs expression was highly linked with the presence of gross perforation, low TSR, high tumor budding (TB) score, high grade, advanced stage, the existence of lymph node (LN) metastasis, DM, necrosis, LVI, PNI, DFS, mortality, and OS. Positive LAG-3 TILs expression was highly correlated with large tumor size, gross perforation, low TSR, high TB score, high grade, advanced phase, the presence of LN, necrosis, LVI, PNI, relapse DFS, mortality, and OS. High Tim-3 epithelial expression was extremely linked with low TSR, advanced phase, the presence of LN, LVI, PNI, relapse, DFS, mortality, and OS, while positive Tim-3 TILs expression was related to gross perforation, low TSR, high TB score, advanced stage, the presence of LN, DM, necrosis, relapse, DFS, mortality, and OS. The patients' poor prognosis may be related to the immunohistochemistry expression of LAG-3, Tim-3, and CTLA-4 in CRC cancer tissue and TILs. Poor patient consequences can result from the CTLA-4, Tim-3, and LAG-3 co-expression, but CTLA-4 TILs' expression of these proteins may inhibit the growth of tumors.

Upper Urinary Tract Urothelial Cancer After Radical Cystectomy for Bladder Cancer: Survival Outcomes After Radical Nephroureterectomy.

Systemic and local recurrences of urothelial bladder cancer (UBC) significantly impair survival after radical cystectomy (RC), but little is known about the impact of the recurrence of urothelial cancer in the upper urinary tract (UTUC). This report describes survival outcomes and their predictors for patients who underwent RC followed by radical nephroureterectomy (RNU) for UTUC. The Surveillance, Epidemiology, and End Results database was queried to identify patients who underwent RC for UBC and subsequent RNU for UTUC. The Kaplan-Meier method and competing-risk Cox regression (CRR) were used for the survival analysis. Overall, 102 patients have undergone RNU within a median of 49 months (interquartile range [IQR], 27-76 months) since RC. Muscle-invasive UTUCs were predominant at RNU (n = 58; 56.7%), but organ-confined bladder tumors were most frequent at RC (n = 42, 41.5%). After RNU, the estimated 5-year overall survival (OS) was 25.9%, the cancer-specific survival (CSS) was 35.6%, the median OS was 23 months (IQR, 11-63 months), and the CSS was 34 months (IQR, 13-132 months). In the multivariable CRR, the factors predictive for CSSafter RNUincluded male gender (hazard ratio [HR], 2.36; 95% confidence interval [CI], 1.03-5.42; p < 0.05), muscle-invasive UTUC (HR, 2.20; 95% CI, 1.13-4.28; p < 0.05), and the presence of distant metastasis (HR,11.59; 95% CI, 5.33-25.2; p < 0.001). In conclusion, the patients who underwent RNU for UTUC after RC for UBC experienced poor OS and CSS. The majority of RNUs were performed for locally advanced tumors. The independent risk factors for worse OS and CSS after RNU were UTUC T stage, presence of metastasis, and male gender.