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Simple Summary: Current clinical practice guidelines support additional locoregional surgery after local resection of early colorectal cancer when one or more of the following risk factors are present: poor differentiation grade, lymphovascular invasion, deep submucosal invasion, moderate or high tumor budding, and deep margin involvement. The absence of all these risk criteria selects a subgroup of patients with very good prognosis that can safely avoid additional surgery. However, lymph node metastases are only identified in 10–20% of patients who ultimately undergo additional surgery, so that 80–90% of the surgeries turn out to be unnecessary. In this investigation, we find that indicating additional surgery in early colorectal cancer only when either moderate or high tumor budding, poorly differentiated clusters, or lymphovascular invasion are present could reduce unnecessary surgeries by 40–45% without significantly increasing the proportion of patients with lymph node metastases who are not offered additional surgery. Background: The low positive predictive value for lymph node metastases (LNM) of common practice risk criteria (CPRC) in T1 colorectal carcinoma (CRC) leads to manyunnecessary additional surgeries following local resection. This study aimed to identify criteria that may improve on the CPRC. Methods: Logistic regression analysis was performed to determine the association of diverse variables with LNM or 'poor outcome' (LNM and/or distant metastases and/or recurrence) in a single center T1 CRC cohort. The diagnostic capacity of the set of variables obtained was compared with that of the CPRC. Results: The study comprised 161 cases. Poorly differentiated clusters (PDC) and tumor budding grade > 1 (TB > 1) were the only independent variables associated with LNM. The area under the curve (AUC) for these criteria was 0.808 (CI 95% 0.717–0.880) compared to 0.582 (CI 95% 0.479–0.680) for CPRC. TB > 1 and lymphovascular invasion (LVI) were independently associated with 'poor outcome', with an AUC of 0.801 (CI 95% 0.731–0.859), while the AUC for CPRC was 0.691 (CI 95% 0.603–0.752). TB > 1, combined either with PDC or LVI, would reduce false positives between 41.5% and 45% without significantly increasing false negatives. Conclusions: Indicating additional surgery in T1 CRC only when either TB > 1, PDC, or LVI are present could reduce unnecessary surgeries significantly. [ABSTRACT FROM AUTHOR]

Encoded by the CDX2 homeobox gene, the CDX2 protein assumes the role of a pivotal transcription factor localized within the nucleus of intestinal epithelial cells, orchestrating the delicate equilibrium of intestinal physiology while intricately guiding the precise development and differentiation of epithelial tissue. Emerging research has unveiled that positive immunohistochemical expression of this protein shows that the CDX2 gene exerts a potent suppressive impact on tumor advancement in colorectal cancer, impeding the proliferation and distant dissemination of tumor cells, while the inhibition or suppression of CDX2 frequently correlates with aggressive behavior in colorectal cancer. In this study, we conducted an immunohistochemical assessment of CDX2 expression on a cohort of 43 intraoperatively obtained tumor specimens from patients diagnosed with colon cancer at Colțea Clinical Hospital in Bucharest, between April 2019 and December 2023. Additionally, we shed light on the morphological diversity within colon tumors, uncovering varying differentiation grades within the same tumor, reflecting the variations in CDX2 expression as well as the genetic complexity underlying these tumors. Based on the findings, we developed an innovative immunohistochemical scoring system that addresses the heterogeneous nature of colon tumors. Comprehensive statistical analysis of CDX2 immunohistochemical expression unveiled significant correlations with known histopathological parameters such as tumor differentiation grades (p-value = 0.011) and tumor budding score (p-value = 0.002), providing intriguing insights into the complex involvement of the CDX2 gene in orchestrating tumor progression through modulation of differentiation processes, and highlighting its role in metastatic predisposition. The compelling correlation identified between CDX2 expression and conventional histopathological parameters emphasizes the prognostic significance of the CDX2 biomarker in colon cancer. Moreover, our novel immunohistochemical scoring system reveals a distinct subset of colon tumors exhibiting reserved prognostic outcomes, distinguished by their "mosaic" CDX2 expression pattern. [ABSTRACT FROM AUTHOR]

Encoded by the CDX2 homeobox gene, the CDX2 protein assumes the role of a pivotal transcription factor localized within the nucleus of intestinal epithelial cells, orchestrating the delicate equilibrium of intestinal physiology while intricately guiding the precise development and differentiation of epithelial tissue. Emerging research has unveiled that positive immunohistochemical expression of this protein shows that the CDX2 gene exerts a potent suppressive impact on tumor advancement in colorectal cancer, impeding the proliferation and distant dissemination of tumor cells, while the inhibition or suppression of CDX2 frequently correlates with aggressive behavior in colorectal cancer. In this study, we conducted an immunohistochemical assessment of CDX2 expression on a cohort of 43 intraoperatively obtained tumor specimens from patients diagnosed with colon cancer at Colțea Clinical Hospital in Bucharest, between April 2019 and December 2023. Additionally, we shed light on the morphological diversity within colon tumors, uncovering varying differentiation grades within the same tumor, reflecting the variations in CDX2 expression as well as the genetic complexity underlying these tumors. Based on the findings, we developed an innovative immunohistochemical scoring system that addresses the heterogeneous nature of colon tumors. Comprehensive statistical analysis of CDX2 immunohistochemical expression unveiled significant correlations with known histopathological parameters such as tumor differentiation grades (p-value = 0.011) and tumor budding score (p-value = 0.002), providing intriguing insights into the complex involvement of the CDX2 gene in orchestrating tumor progression through modulation of differentiation processes, and highlighting its role in metastatic predisposition. The compelling correlation identified between CDX2 expression and conventional histopathological parameters emphasizes the prognostic significance of the CDX2 biomarker in colon cancer. Moreover, our novel immunohistochemical scoring system reveals a distinct subset of colon tumors exhibiting reserved prognostic outcomes, distinguished by their “mosaic” CDX2 expression pattern.

Objective: To analyze the association of apparent diffusion coefficient (ADC) values measured by readout-segmented echo-planar imaging (rs-EPI) using different simultaneous multislice (SMS) acceleration factors and the differentiation of rectal cancer grade. Materials and methods: Patients with non-mucinous rectal adenocarcinoma diagnosed by biopsy (endoscope-guided biopsy or surgical resection) were retrospectively collected, and each patient underwent an MRI examination. ADC values of rs-EPI, 2 × SMS rs-EPI, and 3 × SMS rs-EPI were recorded as ADC1, ADC2, and ADC3, respectively. Results: The scanning time of 2 × SMS rs-EPI was 60 s, 56.2% shorter than 137 s of rs-EPI sequence, while that of 3 × SMS rs-EPI was 51 s, 72.8% less than that of rs-EPI time. The ADC value of the three groups dropped with the decrease in cancer grade (p < 0.05). The AUC values of ADC1, ADC2, and ADC3 in predicting highly differentiated rectal cancer were 0.74, 0.729, and 0.687, respectively. The difference in AUC values between ADC1 and ADC2 was not statistically significant (p = 0.889). Discussion: SMS technology with an acceleration factor of 2 could be applied clinically to evaluate the pathological differentiation of rectal cancer grade. [ABSTRACT FROM AUTHOR]

Background: Venous invasion (VI) in pathological examination of surgically resected gastric cancer (GC) may predict postoperative recurrence, but there are no objective criteria for VI grading. Methods: 157 GC patients (pathological stages I 82, II 34, and III 41) who underwent surgery with curative intent were analyzed. VI was graded in pathological examination by elastica van Gieson staining based on the number of VIs per glass slide as follows: v0, 0; v1, 1−3; v2, 4−6; and v3, ≥ 7. Filling-type invasion in veins with a minor axis of ≥ 1 mm increased the grade by 1. The association of VI grade with prognosis was statistically analyzed. Results: Recurrence increased with VI grade (v0 1.5%, v1 29.6%, v2 41.7%, v3 78.6%). VI grade as well as pathological (p) tumor, node, metastasis (TNM) stage was a significant recurrence predictor by the multivariate Cox analysis. VI grade was implicated in hematogenous and peritoneal recurrences independent of pTNM stage but not in nodal recurrence. GC was then divided into two tiers, without indication of adjuvant chemotherapy (AC) (pStage I, pT1 and pT3N0) and with AC indication (pStages remaining II/III), based on the ACTS-GC trial, which is common in Japan and East Asia. VI grade was a significant recurrence predictor in both tiers. v2/v3 revealed a significantly worse recurrence-free survival (RFS) than v0/v1 in GC without AC indication. v0/v1 exhibited RFS rate exceeding 95% even after 5 years but that of v2/v3 fell around 70% within one year postoperatively, suggesting that AC may be considered for this tier with v2/v3. GC with AC indication exhibited dismal RFS according to the VI grade. RFS rate fell below 80% within one year postoperatively when VI was positive, while recurrence was not observed in v0, which was, however, rare in this tier (10.9%). Differentiation grade did not significantly affect postoperative prognosis in both tiers. Conclusions: VI grade was a significant predictor of postoperative GC recurrence irrespective of the AC indication based on the ACTS-GC study and this VI grading system could be applied in future studies of adjuvant therapy in GC presently deemed without AC indication in Japan. [ABSTRACT FROM AUTHOR]

Background: Influencing factors varied among gastric cancer (GC) for different differentiation grades which affect the prognosis accordingly. This study aimed to develop a nomogram to effectively identify the overall survival (OS). Methods: Totally, 9,568 patients with GC were obtained from the SEER database as the training cohort and internal validation cohort. We then retrospectively enrolled patients diagnosed with GC to construct the external validation cohort from the First Affiliated Hospital of Anhui Medical University. The prognostic factors were integrated into the multivariate Cox regression to construct a nomogram. To test the accuracy of the model, we used the calibration curves, receiver operating characteristics (ROC) curves, C-index, and decision curve analysis (DCA). Results: Race chemotherapy, tumor size, and other four factors were significantly associated with the prognosis of Grade III GC Patients. On this basis, we developed a nomogram. The discrimination of the nomogram revealed good prognostic accuracy The results of the area under the curve (AUC) calculated by ROC for five-year survival were 0.828 and 0.758 in the training set and external validation cohort, higher than that of the TNM staging system. The calibration plot revealed that the estimated risk was close to the actual risk. DCA also suggested an excellent predictive value of the nomogram. Similar results were obtained in Grade-I and Grade-II GC patients. Conclusions: The nomogram developed in this study and other findings could help individualize the treatment of GC patients and assist clinicians in their shared decision-making with patients. [ABSTRACT FROM AUTHOR]

A combination of tumour size, differentiation grade and location may identify a group of vulvar squamous cell cancer (VSCC) patients with a very low risk of inguinal lymph node metastasis. We aim to examine these findings in a large national cohort of VSCC patients. Population based prospective data on VSCC patients treated with vulvectomy and primary groin surgery was obtained from the Danish Gynaecological Cancer Database. Univariate chi-square and multivariate logistic regression analysis were used. Statistical tests were 2-sided. P -values of <0.05 were considered statistically significant. In all, 388 VSCC patients were identified. Of these 264 (63.3%) were node negative and 121 (36.7%) node positive. Increasing tumour size (diameter ≤ 2 cm vs. > 2 to 4 cm), grade (1 vs. 2–3) and location of tumour to clitoris were all associated with a significantly increased risk of inguinal lymph node metastasis OR 2.81(95% CI 1.52–5.20), OR 3.19 (95% CI 1.77–5.74) and OR 2.74 (95% CI 1.56–5.20), respectively. Previous vulvar disease was not associated with lymph node metastasis. No lymph node metastasis was demonstrated in patients with grade 1 tumours, tumour size less than 2 cm and located outside the clitoris area (n = 51). VSCC patients with grade 1 tumours, ≤ 2 cm and without clitoral involvement have a very low risk of inguinal lymph node metastasis. These patients may be spared inguinal lymph node staging to decrease operating time and peri- and postoperative morbidity in the future. However, studies validating our findings are needed. • Tumour size, grade and clitoral involvement are associated with inguinal lymph node metastasis. • Grade 1 tumours, ≤2 cm and no clitoral involvement have low risk of metastatic disease. • Conservative treatment with no groin surgery can be performed in low risk groups. [ABSTRACT FROM AUTHOR]

Objective: to determine the level of growth factors in the blood serum of patients with left-sided colon cancer and to assess the feasibility of using these findings in the tumor detection.Material and Methods. The study group included 63 patients aged 20 to 75 years who underwent surgery for left-sided colon adenocarcinoma (descending, sigmoid, rectosigmoid) with stage i (t1–2n0m0), ii (t3–4an0m0), and iii (t1–2n1m0). Only 5 patients developed metastases in one regional lymph node. The remaining patients had no regional metastases. In all patients, before hospitalization, the tumor was confirmed by colonoscopy followed by histological examination. The group of comparison consisted of 25 patients with chronic hemorrhoids without exacerbation, who underwent colonoscopy. In patients of the study group, blood tests were drawn on the day of surgery before its starting. In patients of the comparison group, blood was taken after excluding colon cancer (after colonoscopy). Blood tests were carried out using a test system (Biolegend): multiplex set for determining growth factors (angiopoietin-2, (ang-2), egf, epo, FGF-basic, G-csf, GM-csf, HGF, M-csf, pdgf-aa, pdgf-BB, scf, tgf-α, vegf).Results. In cancer patients, the levels of egf, HGF, M-csf, pdgf-aa, and pdgf-BB were several times higher than in the control group (p

Abstract Background The clinical relevance of pancreatic intraepithelial neoplasia (PanIN) at the resection margin of pancreatic ductal adenocarcinoma remains unknown. We aimed to investigate its clinical impact at the pancreatic transection margin (PTM) and, based on the result, determine the prognostic values of the resection margin status and other clinicopathologic parameters. Patients and methods We retrospectively analyzed 122 consecutive patients who underwent pancreatoduodenectomy or distal pancreatectomy between 2006 and 2018. Pathologic slides were reviewed and survival data were retrieved from institutional databases. Associations between two variables were investigated by Fisher’s exact test. Survival curves were generated by the Kaplan-Meier method. Prognostic factors were assessed using Cox regression analysis. Results Tumors were resected without leaving macroscopic remnants. The median follow-up period after surgery was 524.5 days. Cancer-related death (n = 72) was marginally and significantly associated with local recurrence (n = 22) and distant metastasis (n = 79), respectively. Local recurrence and distant metastasis occurred independently. After excluding cases with invasive cancer at any other margin, PanIN-2 or PanIN-3 (n = 21) at the PTM did not adversely affect prognoses compared with normal mucosa or PanIN-1 (n = 57) with statistical significance. R0 resection (n = 78), which is invasive cancer-free at all resection margins, showed somewhat better local recurrence-free and overall survivals as compared with R1 resection (n = 44), which involves invasive cancer at any resection margin, but the differences did not reach statistical significance. In contrast, differentiation grade and nodal metastasis were significant predictors of distant metastasis, and tumor location and differentiation grade were significant predictors of cancer-related death. Although there was no significant difference in differentiation grade between the head cancer and the body or tail cancer, nodal metastasis was significantly more frequent in the former than in the latter. Conclusions PanINs at the PTM did not adversely affect prognosis and R0 resection was not found to be a significant prognostic factor. Differentiation grade might be an indicator of occult metastasis and affect patients’ overall survival through distant metastasis. In addition to successful surgical procedures, tumor biology may be even more important as a predictor of postoperative prognosis.

Background: Prognostic relevance of differentiation grade has remained controversial in gastric adenocarcinoma (GAC) after curative resection., Methods: GAC patients who underwent curative gastrectomy were analyzed. Differentiation grade was evaluated according to either the most predominant or least differentiated component. Impacts of clinicopathologic parameters on postoperative recurrence and nodal metastasis were analyzed by the multivariate Cox regression analysis in pT1/2/3/4a and pT1b/2/3 GAC and by the logistic regression analysis in pT1b GAC, respectively., Results: 154 patients with GAC, consisting of 34 pT1a (recurrence rate 0%), 45 pT1b (4.4%), 18 pT2 (22.2%), 40 pT3 (35.0%), and 17 pT4a (76.5%), were included. In pT1/2/3/4a GAC, recurrence was significantly associated with only depth of invasion (pT) and grade of venous invasion (VI), although either mode of differentiation grade was significantly associated with pT by the Spearman's rank correlation test. Next, given no recurrence in pT1a and high-grade histopathology in nearly all pT4a, pT1b/2/3 GAC was analyzed, revealing that recurrence was significantly associated with only VI grade and nodal metastasis. Finally, nodal metastasis was not found in any pT1a GAC, of which 44.1% was predominantly high-grade. In pT1b GAC, nodal metastasis was irrelevant to either mode of differentiation grade, tumor size, and ulceration status but was only associated with lymphatic invasion, suggesting that endoscopic resection of pT1 GAC with negative margin can be curative even with high-grade histopathology., Conclusion: Either mode of differentiation grade revealed limited prognostic relevance after curative gastrectomy. Our results may warrant a controversy over current curability evaluation of endoscopic GAC resection., Competing Interests: Declaration of competing interest None of the authors declares any competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The incidence of neuroendocrine tumors has significantly increased over the last years.The purpose of the study was to analyze treatment outcomes in patients with pancreatic endocrine tumors (PETs) with regard to histopathologic diagnosis.Material and Methods. The clinical records of 1077 patients with pancreatic tumors were retrospectively analyzed. Fifty patients were diagnosed with PET. Treatment outcomes were assessed with regard to tumor differentiation grade, tumor stage, extent of surgery and drug therapy.Results. The most common histological grade was G1. Patients with G1 tumors had the best 1-and 3-year survival rates regardless of tumor stage. Factors influencing prognosis in patients with PETs were: radical surgery, Ki67 expression level, histological grade (G1–3), tumor stage at diagnosis.

Background: Benzo[a]pyrene (BaP) is an endocrine-disrupting pollutant formed during incomplete combustion of organic materials. It has been recognized as a reproductive and developmental toxicant, however epidemiological evidence of the long-term effect of ambient air BaP on breast cancer (BC) is limited. Thus we evaluated associations between ambient air BaP exposure and risk of BC, overall and according to menopausal status and molecular subtypes (estrogen receptor negative/positive (ER−/ER+) and progesterone receptor negative/positive (PR−/PR+)), stage and grade of differentiation of BC in the French E3N cohort study. Methods: Within a nested case-control study of 5222 incident BC cases and 5222 matched controls, annual BaP exposure was estimated using a chemistry-transport model (CHIMERE) and was assigned to the geocoded residential addresses of participants for each year during the 1990–2011 follow-up period. Multivariable conditional logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Results: Overall, cumulative airborne BaP exposure was significantly associated with the overall risk of BC, for each 1 interquartile range (IQR) increase in the concentration levels of BaP (1.42 ng/m3), the OR = 1.15 (95% CI: 1.04–1.27). However, by menopausal status, the significant positive association remained only in women who underwent menopausal transition (i.e. premenopausal women at inclusion who became postmenopausal at diagnosis), OR per 1 IQR = 1.20 (95% CI: 1.03–1.40). By hormone receptor status, positive associations were observed for ER+, PR + and ER + PR + BC, with ORs = 1.17 (95% CI: 1.04–1.32), 1.16 (95% CI: 1.01–1.33), and 1.17 (95% CI: 1.01–1.36) per 1 IQR, respectively. There was also a borderline positive association between BaP and grade 3 BC (OR per 1 IQR = 1.15 (95% CI: 0.99–1.34). Conclusions: We provide evidence of increased risk of BC associated with cumulative BaP exposure, which varied according to menopausal status, hormone receptor status, and grade of differentiation of BC. Our results add further epidemiological evidence to the previous experimental studies suggesting the adverse effects of BaP.

• In the present study IASLC/ATS/ERS classification was useful to identify a high risk population of developing brain metastases in advanced lung adenocarcinoma. • The solid predominant histologic subtype consistently had a significantly higher probability of developing brain metastases even after adjusting by the histological grade and cofounding variables. • According to the histologic grade, moderately differentiated tumors had the highest risk of brain affection irrespective of the lung predominant adenocarcinoma subtype. • IASLC/ATS/ERS classification might suggest more aggressive clinical approaches and closer monitoring in patients with increased hazards for brain metastases development, integrating this classification for risk stratification. Brain metastases (BM) are frequent among lung cancer patients, affecting prognosis and quality of life. The International Association for the Study of Lung Cancer (IASLC), American Thoracic Society (ATS) and European Respiratory Society (ERS) lung adenocarcinoma (LADC) classification (IASLC/ATS/ERS) has prognostic impact in early-stage disease; however, its role in the advanced setting is not precise. This study aims to determine the correlation between the predominant histological subtype and the risk of developing brain metastases (BM) in locally advanced and metastatic (stages IIIB-IV) LADC. A total of 710 patients with LADC were treated at our institution from January 2010 to December 2017. After excluding patients with brain metastases at diagnoses (n = 151), they were categorized according to the IASLC/ATS/ERS LADC classification to estimate the risk of developing brain metastases. A competing risk analysis was employed, considering death a competing risk event. From 559 patients, the mean age was 59 ± 13.2 years, women (52.4 %), and clinical-stage IV (79.2 %). LADC subtypes distribution was lepidic (11.6 %), acinar (37.9 %), papillary (10.2 %), micropapillary (6.8 %), and solid (33.5 %). A total of 27.0 % of patients developed BM, 32.9 % died without brain affection, and 40.0 % did not progress. The predominantly solid subtype showed the greatest probability of all subtypes for developing BM [HR 4.0; 95 % CI (1.80−8.91), p = 0.0006], followed by micropapillary [HR1.11; 95 % CI (0.36−3.39), p = 0.85). The solid subtype, moderately differentiated tumors, age, and ECOG PS (>2) were associated with increased hazards in the multivariate analysis. According to the IASLC/ATS/ERS classification, the predominantly solid pattern was significantly associated with an increased risk of developing BM in patients with locally advanced and metastatic LADC. Its prognostic value might help explore novel clinical approaches, modify monitoring for earlier detection, prevent complications, and reduce morbidity. [ABSTRACT FROM AUTHOR]

ObjectivesTo study clinical characteristics and factors that may affect the prognosis of testicular sarcoma patients.Patients and MethodsIn the Surveillance Epidemiology and End Results database (2006–2016), people with testicular sarcoma were enrolled in our research. Multivariable Cox proportional hazard model and Multivariable Logistic regression model were used to compare the impact of different factors on cancer-specific survival, localized metastasis, and distant metastasis.ResultsThis research was based on the registry information of 158 testicular sarcoma patients. All patients with a median age of 17.00 (1.00–93.00) years were pathologically diagnosed with orchiectomy or needle biopsy specimens. Patients with Grade I, II, III, and IV testicular sarcoma accounted for 34.29% (n = 24), 10.10% (n = 7), 22.86% (n = 16), and 32.86% (n = 23) of all patients, respectively. There were 42 (30.43%), 53 (38.41%), 15 (10.87%), 20 (14.49%), 5 (3.62%), 3 (2.17%) patients with Tis, T1, T2, T3, T4, and >T4 (the invasion degree exceeded the staging system of testicular cancer) disease respectively. Among all included patients, localized metastasis occurred in 31 (20.13%) patients, distant metastasis was found in 28 (18.18%) patients during observation, and 61.69% (n = 95) had no metastasis. Thirty-two (20.25%) patients died of this cancer. According to our study, patients with distant metastasis [OR = 17.86, 95% CI (4.63–68.84), p < 0.0001] and T3 disease [OR = 4.13, 95% CI (1.10–15.53), p = 0.0359] were more likely to die of this cancer. Patients with advanced T stage were more likely to occur distant metastasis, [OR = 13.91, 95% CI (1.80–107.54), p = 0.0116] for T3 and [OR = 16.36, 95% CI (1.36–196.21), p = 0.0275] for T4.ConclusionsAccording to our research, factors including metastasis and higher T stage were significantly related with poorer prognosis of testicular sarcoma. Higher T stage was also found to be a risk factor of distant metastasis. The recognization of these poor prognostic factors may allow physicians to make comprehensive and appropriate management decision for testicular sarcoma patients.

Objectives: To study clinical characteristics and factors that may affect the prognosis of testicular sarcoma patients. Patients and Methods: In the Surveillance Epidemiology and End Results database (2006–2016), people with testicular sarcoma were enrolled in our research. Multivariable Cox proportional hazard model and Multivariable Logistic regression model were used to compare the impact of different factors on cancer-specific survival, localized metastasis, and distant metastasis. Results: This research was based on the registry information of 158 testicular sarcoma patients. All patients with a median age of 17.00 (1.00–93.00) years were pathologically diagnosed with orchiectomy or needle biopsy specimens. Patients with Grade I, II, III, and IV testicular sarcoma accounted for 34.29% (n = 24), 10.10% (n = 7), 22.86% (n = 16), and 32.86% (n = 23) of all patients, respectively. There were 42 (30.43%), 53 (38.41%), 15 (10.87%), 20 (14.49%), 5 (3.62%), 3 (2.17%) patients with Tis, T1, T2, T3, T4, and >T4 (the invasion degree exceeded the staging system of testicular cancer) disease respectively. Among all included patients, localized metastasis occurred in 31 (20.13%) patients, distant metastasis was found in 28 (18.18%) patients during observation, and 61.69% (n = 95) had no metastasis. Thirty-two (20.25%) patients died of this cancer. According to our study, patients with distant metastasis [OR = 17.86, 95% CI (4.63–68.84), p < 0.0001] and T3 disease [OR = 4.13, 95% CI (1.10–15.53), p = 0.0359] were more likely to die of this cancer. Patients with advanced T stage were more likely to occur distant metastasis, [OR = 13.91, 95% CI (1.80–107.54), p = 0.0116] for T3 and [OR = 16.36, 95% CI (1.36–196.21), p = 0.0275] for T4. Conclusions: According to our research, factors including metastasis and higher T stage were significantly related with poorer prognosis of testicular sarcoma. Higher T stage was also found to be a risk factor of distant metastasis. The recognization of these poor prognostic factors may allow physicians to make comprehensive and appropriate management decision for testicular sarcoma patients. [ABSTRACT FROM AUTHOR]

Background: The study on predicting the differentiation grade of colorectal cancer (CRC) based on magnetic resonance imaging (MRI) has not been reported yet. Developing a non-invasive model to predict the differentiation grade of CRC is of great value., Aim: To develop and validate machine learning-based models for predicting the differentiation grade of CRC based on T2-weighted images (T2WI)., Methods: We retrospectively collected the preoperative imaging and clinical data of 315 patients with CRC who underwent surgery from March 2018 to July 2023. Patients were randomly assigned to a training cohort ( n = 220) or a validation cohort ( n = 95) at a 7:3 ratio. Lesions were delineated layer by layer on high-resolution T2WI. Least absolute shrinkage and selection operator regression was applied to screen for radiomic features. Radiomics and clinical models were constructed using the multilayer perceptron (MLP) algorithm. These radiomic features and clinically relevant variables (selected based on a significance level of P < 0.05 in the training set) were used to construct radiomics-clinical models. The performance of the three models (clinical, radiomic, and radiomic-clinical model) were evaluated using the area under the curve (AUC), calibration curve and decision curve analysis (DCA)., Results: After feature selection, eight radiomic features were retained from the initial 1781 features to construct the radiomic model. Eight different classifiers, including logistic regression, support vector machine, k-nearest neighbours, random forest, extreme trees, extreme gradient boosting, light gradient boosting machine, and MLP, were used to construct the model, with MLP demonstrating the best diagnostic performance. The AUC of the radiomic-clinical model was 0.862 (95%CI: 0.796-0.927) in the training cohort and 0.761 (95%CI: 0.635-0.887) in the validation cohort. The AUC for the radiomic model was 0.796 (95%CI: 0.723-0.869) in the training cohort and 0.735 (95%CI: 0.604-0.866) in the validation cohort. The clinical model achieved an AUC of 0.751 (95%CI: 0.661-0.842) in the training cohort and 0.676 (95%CI: 0.525-0.827) in the validation cohort. All three models demonstrated good accuracy. In the training cohort, the AUC of the radiomic-clinical model was significantly greater than that of the clinical model ( P = 0.005) and the radiomic model ( P = 0.016). DCA confirmed the clinical practicality of incorporating radiomic features into the diagnostic process., Conclusion: In this study, we successfully developed and validated a T2WI-based machine learning model as an auxiliary tool for the preoperative differentiation between well/moderately and poorly differentiated CRC. This novel approach may assist clinicians in personalizing treatment strategies for patients and improving treatment efficacy., Competing Interests: Conflict-of-interest statement: All the Authors have no conflict of interest related to the manuscript., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background/Aims: Owing to the lack of effective molecular markers to evaluate colon cancer differentiation grade, screening of effective molecular markers for the diagnosis and treatment of colon cancer is of great significance. This study is a screening study for molecular markers related to the differentiation of colon using the tissue-specific genes of colon. Methods: This study compared the expression profiles of colon cancer at various differentiation grades and screened the down-regulated genes associated with decreased differentiation. IL22RA1 gene was derived from the intersection of obtained gene and colon tissue-specific genes. We used DriverDB and The Human Protein Atlas to analyze the expression level of IL22RA1 in various tissue cells, also used Kaplan-Meier method to analyze the correlation between IL22RA1 and the survival of colon cancer patients, and then used the ROC curve to analyze the specificity and sensitivity of IL22RA1 diagnosis of differentiated colon cancer. Results: We found that IL22RA1 gene expression was progressively down-regulated in high-differentiated, moderate-differentiated, low-differentiated, and undifferentiated colon cancer tissues. Both RNA and protein levels of IL22RA1 were higher in colon tissues and colon cancer tissues than in other normal and cancer tissues. Comparison of IL22RA1 expression in different cancer cells found that IL22RA1 expression was significantly higher in CACO-2 colon cancer cells than in other cancer cells. Survival analysis showed that IL22RA1 gene expression was positively correlated with the overall survival rate of colon cancer patients (P=0.0224). ROC curve analysis revealed that IL22RA1 expression had good specificity and sensitivity to stage II colon cancer. Conclusion: These findings suggest that IL22RA1 serves as a specific molecular marker for the differentiation of colon cancer.

Background: The clinical relevance of pancreatic intraepithelial neoplasia (PanIN) at the resection margin of pancreatic ductal adenocarcinoma remains unknown. We aimed to investigate its clinical impact at the pancreatic transection margin (PTM) and, based on the result, determine the prognostic values of the resection margin status and other clinicopathologic parameters. Patients and methods: We retrospectively analyzed 122 consecutive patients who underwent pancreatoduodenectomy or distal pancreatectomy between 2006 and 2018. Pathologic slides were reviewed and survival data were retrieved from institutional databases. Associations between two variables were investigated by Fisher's exact test. Survival curves were generated by the Kaplan-Meier method. Prognostic factors were assessed using Cox regression analysis. Results: Tumors were resected without leaving macroscopic remnants. The median follow-up period after surgery was 524.5 days. Cancer-related death (n = 72) was marginally and significantly associated with local recurrence (n = 22) and distant metastasis (n = 79), respectively. Local recurrence and distant metastasis occurred independently. After excluding cases with invasive cancer at any other margin, PanIN-2 or PanIN-3 (n = 21) at the PTM did not adversely affect prognoses compared with normal mucosa or PanIN-1 (n = 57) with statistical significance. R0 resection (n = 78), which is invasive cancer-free at all resection margins, showed somewhat better local recurrence-free and overall survivals as compared with R1 resection (n = 44), which involves invasive cancer at any resection margin, but the differences did not reach statistical significance. In contrast, differentiation grade and nodal metastasis were significant predictors of distant metastasis, and tumor location and differentiation grade were significant predictors of cancer-related death. Although there was no significant difference in differentiation grade between the head cancer and the body or tail cancer, nodal metastasis was significantly more frequent in the former than in the latter. Conclusions: PanINs at the PTM did not adversely affect prognosis and R0 resection was not found to be a significant prognostic factor. Differentiation grade might be an indicator of occult metastasis and affect patients' overall survival through distant metastasis. In addition to successful surgical procedures, tumor biology may be even more important as a predictor of postoperative prognosis. [ABSTRACT FROM AUTHOR]

Ｏｂｊｅｃｔｉｖｅ Ｔｏ ｉｎｖｅｓｔｉｇａｔｅ ｔｈｅ ｄｉｆｆｅｒｅｎｃｅｓ ｏｆ ｇｅｍｓｔｏｎｅ ｓｐｅｃｔｒａｌ ｃｕｒｖｅ ａｎｄ ＣＴ ｖａｌｕｅ ｏｆ ｇａｓｔｒｉｃ ｃａｎｃｅｒ ｗｉｔｈ ｄｉｆｆｅｒｅｎｔ ｐａｔｈｏｌｏｇｉｃａｌ ｔｙｐｅｓ ａｎｄ ｄｉｆｆｅｒｅｎｔｉａｔｉｏｎ ｄｅｇｒｅｅｓ． Ｍｅｔｈｏｄｓ ９１ ｃａｓｅｓ ｏｆ ｐｒｅｏｐｅｒａｔｉｖｅ ｇｅｍｓｔｏｎｅ ＣＴ ｉｍａｇｅｓ ｗｉｔｈ ｇａｓｔｒｉｃ ｃａｎｃｅｒ ｗｅｒｅ ｃｏｌｌｅｃｔｅｄ， ｉｎｃｌｕｄｉｎｇ ２４ ｃａｓｅｓ ｏｆ ｍｕｃｉｎｏｕｓ ｃａｒｃｉｎｏｍａ， ６７ ｃａｓｅｓ ｏｆ ｎｏｎ⁃ｍｕｃｉｎｏｕｓ ｃａｒｃｉｎｏｍａ， １６ ｃａｓｅｓ ｏｆ ｓｉｇｎｅｔ ｒｉｎｇ ｃｅｌｌ ｃａｒｃｉｎｏｍａ， ８ ｃａｓｅｓ ｏｆ ｍｕｃｉｎｏｕｓ ａｄｅｎｏｃａｒｃｉｎｏｍａ， ３２ ｃａｓｅｓ ｏｆ ｍｏｄｅｒａｔｅｌｙ ｄｉｆｆｅｒｅｎｔｉａｔｅｄ ａｄｅｎｏｃａｒｃｉｎｏｍａ ａｎｄ ３５ ｃａｓｅｓ ｏｆ ｐｏｏｒｌｙ ｄｉｆｆｅｒｅｎｔｉａｔｅｄ ａｄｅｎｏｃａｒｃｉｎｏｍａ． Ｇｅｍｓｔｏｎｅ ＣＴ ｓｐｅｃｔｒａｌ ｉｍａｇｉｎｇ ｗａｓ ｐｅｒｆｏｒｍｅｄ ｐｒｅｏｐｅｒａｔｉｖｅｌｙ， ａｎｄ ｔｈｅ ｓｐｅｃｔｒａｌ ｃｕｒｖｅ ｏｆ ｔｈｅ ｌｅｓｉｏｎ ｉｎ ｖｅｎｏｕｓ ｐｈａｓｅ ｗａｓ ｏｂｔａｉｎｅｄ ｂｙ ｕｓｉｎｇ ＧＳＩ Ｖｉｅｗｅｒ ｓｏｆｔｗａｒｅ， ｔｈｅ ｓｌｏｐｅ ｏｆ ｔｈｅ ｃｕｒｖｅ ｗａｓ ｃａｌｃｕｌａｔｅｄ， ａｎｄ １１ ｍｏｎｏｅｎｅｒｇｅｔｉｃ ＣＴ ｖａｌｕｅｓ ｏｆ ４０～１４０ ｋｅＶ （１０ ｋｅＶ ｉｎｔｅｒｖａｌ） ｗｅｒｅ ｍｅａｓｕｒｅｄ． Ｔｈｅ ｇｅｍｓｔｏｎｅ ｓｐｅｃｔｒａｌ ｃｕｒｖｅｓ ａｎｄ ＣＴ ｖａｌｕｅｓ ｏｆ ｇａｓｔｒｉｃ ｃａｎｃｅｒ ｗｉｔｈ ｄｉｆｆｅｒｅｎｔ ｐａｔｈｏｌｏｇｉｃａｌ ｔｙｐｅｓ ａｎｄ ｄｉｆｆｅｒｅｎｔｉａｔｉｏｎ ｄｅｇｒｅｅｓ ａｒｅ ｃｏｍｐａｒｅｄ． Ｒｅｓｕｌｔｓ Ｔｈｅ ｃｕｒｖｅ ｓｌｏｐｅｓ ｏｆ ｎｏｎ⁃ｍｕｃｉｎｏｕｓ ｃａｒｃｉｎｏｍａ， ｓｉｇｎｅｔ ｒｉｎｇ ｃｅｌｌ ｃａｒｃｉｎｏｍａ ａｎｄ ｐｏｏｒｌｙ ｄｉｆｆｅｒｅｎｔｉａｔｅｄ ａｄｅｎｏｃａｒｃｉｎｏｍａ ｗｅｒｅ －１．９２±０．５３， －１．７３±０．３７ ａｎｄ －２．１４±０．５４， ｒｅｓｐｅｃｔｉｖｅｌｙ． Ｔｈｅ ａｂｓｏｌｕｔｅ ｖａｌｕｅｓ ｗｅｒｅ ｈｉｇｈｅｒ ｔｈａｎ ｔｈｏｓｅ ｏｆ ｍｕｃｉｎｏｕｓ ｃａｒｃｉｎｏｍａ （－１．４５±０．５４）， ｍｕｃｉｎｏｕｓ ａｄｅｎｏｃａｒｃｉｎｏｍａ （－０．９０± ０．３４） ａｎｄ ｍｏｄｅｒａｔｅｌｙ ｄｉｆｆｅｒｅｎｔｉａｔｅｄ ａｄｅｎｏｃａｒｃｉｎｏｍａ （－１．６７±０．４１）， ａｎｄ ｔｈｅ ｄｉｆｆｅｒｅｎｃｅｓ ｗｅｒｅ ａｌｌ ｓｔａｔｉｓｔｉｃａｌｌｙ ｓｉｇｎｉｆｉｃａｎｔ （Ｐ＜０．０５）． Ｔｈｅｒｅ ｗｅｒｅ ｓｉｇｎｉｆｉｃａｎｔ ｄｉｆｆｅｒｅｎｃｅｓ ｉｎ ｍｏｎｏｅｎｅｒｇｅｔｉｃ ＣＴ ｖａｌｕｅｓ ｂｅｔｗｅｅｎ ｍｕｃｉｎｏｕｓ ａｎｄ ｎｏｎ⁃ｍｕｃｉｎｏｕｓ ｃａｒｃｉｎｏｍａｓ ａｔ ４０⁃１４０ ｋｅＶ （ａｌｌ Ｐ＜０．０５）． Ｔｈｅ ｆｏｒｍｅｒ ｗａｓ ｌｏｗｅｒ ｔｈａｎ ｔｈｅ ｌａｔｔｅｒ ｉｎ ｄｉｆｆｅｒｅｎｔ ｄｅｇｒｅｅｓ， ａｎｄ ｔｈｅ ｌｏｗｅｒ ｔｈｅ ｅｎｅｒｇｙ， ｔｈｅ ｇｒｅａｔｅｒ ｔｈｅ ｄｉｆｆｅｒｅｎｃｅ ｗａｓ． Ｔｈｅｒｅ ｗｅｒｅ ｓｉｇｎｉｆｉｃａｎｔ ｄｉｆｆｅｒｅｎｃｅｓ ｉｎ ｍｏｎｏｅｎｅｒｇｅｔｉｃ ＣＴ ｖａｌｕｅｓ ｂｅｔｗｅｅｎ ｓｉｇｎｅｔ ｒｉｎｇ ｃｅｌｌ ｃａｒｃｉｎｏｍａ ａｎｄ ｍｕｃｉｎｏｕｓ ａｄｅｎｏｃａｒｃｉｎｏｍａ ａｔ ４０⁃１００ ｋｅＶ （ａｌｌ Ｐ ＜ ０． ０５）； ｍｏｎｏｅｎｅｒｇｅｔｉｃ ＣＴ ｖａｌｕｅｓ ｂｅｔｗｅｅｎ ｐｏｏｒｌｙ ｄｉｆｆｅｒｅｎｔｉａｔｅｄ ａｄｅｎｏｃａｒｃｉｎｏｍａ ａｎｄ ｍｏｄｅｒａｔｅｌｙ ｄｉｆｆｅｒｅｎｔｉａｔｅｄ ａｄｅｎｏｃａｒｃｉｎｏｍａ ａｔ ４０⁃９０ ｋｅＶ ｓｈｏｗｅｄ ｓｔａｔｉｓｔｉｃａｌｌｙ ｓｉｇｎｉｆｉｃａｎｔ ｄｉｆｆｅｒｅｎｃｅｓ （ Ｐ ＜ ０． ０５）． Ｃｏｎｃｌｕｓｉｏｎｓ Ｇａｓｔｒｉｃ ｃａｎｃｅｒ ｗｉｔｈ ｄｉｆｆｅｒｅｎｔ ｐａｔｈｏｌｏｇｉｃａｌ ｔｙｐｅｓ ａｎｄ ｄｉｆｆｅｒｅｎｔｉａｔｉｏｎ ｄｅｇｒｅｅｓ ｈａｖｅ ｔｈｅｉｒ ｃｈａｒａｃｔｅｒｉｓｔｉｃ ｓｐｅｃｔｒａｌ ｃｕｒｖｅｓ ｉｎ ｖｅｎｏｕｓ ｐｈａｓｅ， ａｎｄ ｔｈｅ ｍｏｎｏｅｎｅｒｇｅｔｉｃ ＣＴ ｖａｌｕｅｓ ａｒｅ ｓｉｇｎｉｆｉｃａｎｔｌｙ ｄｉｆｆｅｒｅｎｔ ａｔ ｌｏｗ ｅｎｅｒｇｙ． Ｔｈｅ ｓｐｅｃｔｒａｌ ｃｕｒｖｅ ｏｆ ｇｅｍｓｔｏｎｅ ＣＴ ｍａｙ ｂｅ ｈｅｌｐｆｕｌ ｔｏ ｅｖａｌｕａｔｅ ｔｈｅ ｐａｔｈｏｌｏｇｉｃａｌ ｔｙｐｅ ａｎｄ ｄｉｆｆｅｒｅｎｔｉａｔｉｏｎ ｄｅｇｒｅｅ ｏｆ ｇａｓｔｒｉｃ ｃａｎｃｅｒ ｂｅｆｏｒｅ ｏｐｅｒａｔｉｏｎ. [ABSTRACT FROM AUTHOR]

Annexin A7 is a member of the Annexin A family, which participates in various biological processes. Accumulating evidence has demonstrated that Annexin A7 serves an important role in tumorigenesis and is dysregulated in multiple types of cancer. However, the role of Annexin A7 in the tumorigenesis of gastric cancer remains to be determined. The present study revealed that Annexin A7 expression is downregulated in late‑stage gastric cancer and is negatively correlated with the differentiation grade and apoptosis. There was a significant difference in Annexin A7 mRNA and protein expression in gastric cancer samples with distinct differentiation grades, with the lowest expression being observed in the highly differentiated cases. A terminal deoxynucleotidyl‑transferase‑mediated dUTP nick end labelling assay demonstrated that the apoptosis indices of highly, moderately and poorly differentiated gastric cancers were 18.12±2.40, 9.73±1.73 and 4.13±0.83%, respectively, with statistical significance (P<0.05). Flow cytometric analysis demonstrated that the apoptosis rates of gastric cancer MKN74, SGC7901 and BGC823 cells were 10.07±1.21, 7.11±1.04 and 4.25±1.02%, respectively, with statistical significance (P<0.05). Spearman's rank correlation analysis revealed that the Annexin A7 mRNA and protein levels were negatively correlated with the differentiation grade of the gastric cancer tissues, while the apoptosis index was positively correlated with the differentiation grade of the gastric cancer tissues. Furthermore, the apoptosis index was negatively correlated with Annexin A7 mRNA and protein expression. Similar associations were observed among Annexin A7 expression, differentiation grades and apoptosis in gastric cancer cell lines. The results of the present study demonstrated that Annexin A7 expression is downregulated, while apoptosis is upregulated, with the progression of gastric adenocarcinoma. These observations suggested that Annexin A7 may inhibit apoptosis during tumorigenesis and that it is a potential biomarker for the diagnosis, prognosis and treatment of gastric adenocarcinoma. [ABSTRACT FROM AUTHOR]

Introduction In oral squamous cell carcinoma (OSCC) the differentiation grade of the tumor is determined on the biopsy and the resection specimen. The relation between tumor grade, nodal metastasis and survival is debatable. The aims of this study were to determine the correlation between differentiation grade of the biopsy and the resection specimen. Furthermore, we wanted to correlate tumor differentiation grade with nodal stage and survival. Patients and methods One-hundred and forty-five patients with OSCC staged as T1-2, N0 of the tongue, floor of mouth or cheek with primary resection of the tumor were examined. Biopsy and resection specimen were histologically re-assessed with regard to differentiation grade, as well as infiltrative, peri-neural and vascular invasive growth. Results This study showed a poor correlation between differentiation grade in the incisional biopsy and the resection specimen of the same tumor. No significant relation between differentiation grade of the resection specimen and nodal involvement, as well as overall and disease-specific survival was found. Conclusion In early OSCC the differentiation grade determined by biopsy is of little predictive value for the grading of the resection specimen. Poor differentiation grade could not be related to the presence of nodal metastasis or survival and seems not to have any prognostic value concerning outcome. Treatment planning must be related to these findings. [ABSTRACT FROM AUTHOR]

Objective: To analyze the association of apparent diffusion coefficient (ADC) values measured by readout-segmented echo-planar imaging (rs-EPI) using different simultaneous multislice (SMS) acceleration factors and the differentiation of rectal cancer grade., Materials and Methods: Patients with non-mucinous rectal adenocarcinoma diagnosed by biopsy (endoscope-guided biopsy or surgical resection) were retrospectively collected, and each patient underwent an MRI examination. ADC values of rs-EPI, 2 × SMS rs-EPI, and 3 × SMS rs-EPI were recorded as ADC 1 , ADC 2 , and ADC 3 , respectively., Results: The scanning time of 2 × SMS rs-EPI was 60 s, 56.2% shorter than 137 s of rs-EPI sequence, while that of 3 × SMS rs-EPI was 51 s, 72.8% less than that of rs-EPI time. The ADC value of the three groups dropped with the decrease in cancer grade (p < 0.05). The AUC values of ADC 1 , ADC 2, and ADC 3 in predicting highly differentiated rectal cancer were 0.74, 0.729, and 0.687, respectively. The difference in AUC values between ADC 1 and ADC 2 was not statistically significant (p = 0.889)., Discussion: SMS technology with an acceleration factor of 2 could be applied clinically to evaluate the pathological differentiation of rectal cancer grade., (© 2022. The Author(s), under exclusive licence to European Society for Magnetic Resonance in Medicine and Biology (ESMRMB).)

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Reasons for performing study Penile and preputial papilloma and squamous cell carcinoma ( SCC) are commonly diagnosed in horses. Papillomas have the potential to progress to potentially lethal SCC. Knowledge of pathogenetic mechanisms may help in prevention and definition of treatment targets. Study design Retrospective study using archived material. Objectives To determine the expression of cyclo-oxygenase 1 ( COX-1), cyclo-oxygenase 2 ( COX-2) and microsomal prostaglandin E synthase-1 ( mPGES-1) in penile and preputial normal tissue, papilloma and SCC in horses, and whether expression of these enzymes is influenced by degree of inflammation and differentiation grade. Methods Tumour differentiation grade, degree of inflammation and COX-1, COX-2 and mPGES-1 expression in 75 formalin-fixed paraffin embedded samples of penile and preputial papilloma and SCC of 68 horses were investigated by histopathology and immunohistochemistry. Results Inflammation was more prominent in SCC compared with papilloma. No correlation between expression of COX-1 or COX-2 and inflammation was found. Expression of mPGES-1 was weakly correlated with inflammation. Expression of COX-1, COX-2 and mPGES-1 was found in 42.6%, 50.7% and 96.0% of lesions respectively, but less than 1% of cells were immunopositive for COX-1 and COX-2 in 59.4% and 84.2% of cases respectively. Expression of COX-1 was moderately negatively correlated with differentiation grade, COX-2 was not correlated and mPGES-1 was poorly negatively correlated. Conclusions Expression of COX-1 and COX-2 in penile and preputial SCC in the horse is poor and COX inhibitors may thus be of little value for prevention or treatment. Microsomal PGES-1 is more prominently expressed in well-differentiated tissue compared with poorly differentiated tissue. Further research on the role of mPGES-1 in carcinogenesis is needed to assess its potential use as a treatment target. Knowledge of arachidonic pathway enzyme expression and their role in equine penile and preputial carcinogenesis may help in developing preventive and therapeutic strategies. [ABSTRACT FROM AUTHOR]

Background: Influencing factors varied among gastric cancer (GC) for different differentiation grades which affect the prognosis accordingly. This study aimed to develop a nomogram to effectively identify the overall survival (OS)., Methods: Totally, 9,568 patients with GC were obtained from the SEER database as the training cohort and internal validation cohort. We then retrospectively enrolled patients diagnosed with GC to construct the external validation cohort from the First Affiliated Hospital of Anhui Medical University. The prognostic factors were integrated into the multivariate Cox regression to construct a nomogram. To test the accuracy of the model, we used the calibration curves, receiver operating characteristics (ROC) curves, C-index, and decision curve analysis (DCA)., Results: Race chemotherapy, tumor size, and other four factors were significantly associated with the prognosis of Grade III GC Patients. On this basis, we developed a nomogram. The discrimination of the nomogram revealed good prognostic accuracy The results of the area under the curve (AUC) calculated by ROC for five-year survival were 0.828 and 0.758 in the training set and external validation cohort, higher than that of the TNM staging system. The calibration plot revealed that the estimated risk was close to the actual risk. DCA also suggested an excellent predictive value of the nomogram. Similar results were obtained in Grade-I and Grade-II GC patients., Conclusions: The nomogram developed in this study and other findings could help individualize the treatment of GC patients and assist clinicians in their shared decision-making with patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Hu, Yang, Chen, Sun, Wang, Zhu, Yang, Cao, Xiong and Chen.)

Copyright of Der Pathologe is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Purpose: To explore the potential use of magnetic resonance imaging (MRI) in predicting the outcome for patients with hepatocellular carcinoma (HCC), imaging characteristics were correlated with pathological findings and clinical outcome. Materials and Methods: With permission from the Ethical Board, clinical data and tissues of resected HCC patients were collected, including the preoperative MRI. The role of MRI characteristics on recurrence and survival were evaluated with univariate and multivariate analyses. Results: Between January 2000 and December 2008, 87 patients with 104 HCCs were operated on. Microvascular invasion was present in 55 lesions (53%). HCC was characterized as well differentiated in 15 lesions (14%), as moderate in 50 lesions (48%), and as poorly differentiated in 34 lesions (33%). Due to preoperative treatment in five lesions (5%) no vital tumor was left. In 85 lesions (88%) washout of contrast was noted. Of the 87 patients, 28 (32%) with 37 lesions developed HCC recurrence; these patients had microvascular invasion significantly more often and a moderate or poorly differentiated tumor ( P < 0.001 and P = 0.025, respectively). MRI more often showed washout when HCC was moderately or poorly differentiated ( P < 0.001) or microvascular invasion was present ( P = 0.032). Conclusion: Differentiation grade and microvascular invasion are significantly associated with the presence of washout demonstrated on dynamic contrast-enhanced MRI. J. Magn. Reson. Imaging 2012;36:641-647. © 2012 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Background: The thymidine phosphorylase (TP) enzyme has several tumor-promoting functions. The aim of this study was to explore TP gene expression in relation to clinical and histopathological data obtained from patients with stage III colorectal cancer. Methods and results: TP gene expression was analyzed by real-time quantitative PCR in tumor and mucosa samples from 254 patients. TP gene expression in tumors correlated with lymph node staging, with higher expression relating to a higher number of positive nodes and a worse N-stage. Higher TP expression was also associated with a worse histological tumor grade. Patients with rectal cancer had significantly higher TP expression in mucosa and tumors compared with patients having colon cancer. Conclusion: Higher intratumoral TP expression appears to be related to a worse N stage, and thus, with a worse prognosis. TP gene expression measured in a preoperative biopsy could be of interest in preoperative staging. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To examine the associations of measured anthropometric factors, including general and central adiposity, with epithelial ovarian cancer (EOC) risk in the Malmö Diet and Cancer Study. Methods: In 93 incident EOC cases from a Swedish population-based prospective cohort study, seven anthropometric factors; height, weight, BMI, body fat percentage, waist- and hip circumference, and waist-hip ratio (WHR), were categorized by tertiles of baseline anthropometric measurements and relative risks were calculated using multivariate Cox regression models. Results: A high WHR (<0.77, ≥0.77 to <0.81, ≥0.81cm/cm) was associated with a statistically significantly lower overall risk for EOC (RR 0.60; 0.36–1.00; p-trend=0.04), particularly tumours of differentiation grades 1 and 2 (RR 0.27; 0.09–0.81; p-trend=0.03) and clinical stages 1 and 2 (RR 0.32; 0.10–0.97; p-trend=0.03) and these associations were stronger in postmenopausal women. Neither height, weight, BMI, body fat percentage, waist- or hip circumference were associated with overall risk, nor with risk for different subtypes, differentiation grade or stage. Conclusions: These results demonstrate that a high WHR is associated with a decreased risk of EOC. Other anthropometric factors were not associated with EOC risk. [Copyright &y& Elsevier]

Matsumoto E, Nakatsukasa H, Nouso K, Kobayashi Y, Nakamura S, Suzuki M, Takuma Y, Tanaka H, Fujikawa T, Shiratori Y. Increased levels of tissue inhibitor of metalloproteinase-1 in human hepatocellular carcinoma. Liver International 2004: DOI:10.1111/j.1478-3231.2004.0927.x. © Blackwell Munksgaard 2004 Invasion and metastasis of hepatocellular carcinoma (HCC) are regulated by matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs). However, the role of TIMPs in these processes is not clear. To examine the potential involvement of TIMP-1 in HCC and the association between TIMP-1 and clinical outcome of patients with HCC. The study included 91 patients who underwent surgical removal of HCC. TIMP-1 concentrations in the supernatant of tissue homogenates of HCC and non-neoplastic liver were measured by enzyme immunoassay. The relationships between TIMP-1 concentration and various clinicopathological features and recurrence of HCC after surgical operation were examined. The mean level of TIMP-1 in HCC (486±610 ng/mg protein, ±SD) was significantly higher than in the non-neoplastic liver (75±69, P<0.0001). The median level of TIMP-1 in poorly differentiated HCCs (701 ng/mg protein) was significantly higher than in well- (80) and moderately (172) differentiated HCCs ( P=0.0047 and P=0.0082, respectively). TIMP-1 level in liver cirrhosis was higher than in chronic hepatitis ( P=0.0015). TIMP-1 levels in HCC did not influence the recurrence rate of HCC. TIMP-1 concentration in HCC was higher than in non-neoplastic liver and correlated with the differentiation grade of HCCs. However, tissue TIMP-1 concentration does not seem to be an important determinant of HCC recurrence. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate semiquantitative and qualitative analysis of lymphocytic infiltrations in a neoplasm microenvironment in patients with laryngeal cancers and the correlation analysis between the intensitivity degree and composition of lymphocytic infiltration in foreseeing a survival time and probability of the appearance of lymph node metastases. Postoperative specimens from 43 patients (Upper Silesia region) operated on for laryngeal cancer in the 2nd ENT Department, Silesian Medical University in Zabrze between 1985 and 1995 all had unfavorable courses due to tumor recurrences. The patients’ ages ranged from 39 to 79 years (mean 57 years). Tissue specimens were subjected to routine processing. The degree of pathological changes was ascertained and immunohistochemical preparations of laryngeal tissue were prepared according to generally accepted methods. The following primary monoclonal antibodies were used: CD 3, CD 20, CD 43, CD 45 RO, CD 56. The distribution analysis of the intensity of the phenotype CD 43 evaluated the lymphocytic infiltration in relation to differentiation of the whole study group. The intensity of CD 43 cell infiltration increased in the group of patients with lymph node metastases. In patients with stage IV disease, a relationship was found between survival time and intensity of cell infiltrations with CD 43 and CD 45 RO lymphocytes. The influence of these two lymphocyte phenotypes in the patient subgroups – one after total laryngectomy with confirmed lymph node metastases and the other group without lymph node metastases – showed their prognostic value. Our analysis of lymphocytic infiltration, mostly of CD 43 cells, in the neoplasm microenvironment indicated a prognostic value for determining a shorter survival time and the possibility of lymph node metastases in patients with recurrences of cancer. [ABSTRACT FROM AUTHOR]

• First epidemiological study with extended annual exposure data (up to 22 years). • Airborne BaP exposure was significantly associated with overall breast cancer risk. • The association was greater among women who underwent menopausal transition. • Positive associations were observed for ER+, PR+, ER+ PR+, and grade 3 breast cancer. • Significant effect modification was observed for tobacco smoking status. Benzo[a]pyrene (BaP) is an endocrine-disrupting pollutant formed during incomplete combustion of organic materials. It has been recognized as a reproductive and developmental toxicant, however epidemiological evidence of the long-term effect of ambient air BaP on breast cancer (BC) is limited. Thus we evaluated associations between ambient air BaP exposure and risk of BC, overall and according to menopausal status and molecular subtypes (estrogen receptor negative/positive (ER−/ER+) and progesterone receptor negative/positive (PR−/PR+)), stage and grade of differentiation of BC in the French E3N cohort study. Within a nested case-control study of 5222 incident BC cases and 5222 matched controls, annual BaP exposure was estimated using a chemistry-transport model (CHIMERE) and was assigned to the geocoded residential addresses of participants for each year during the 1990–2011 follow-up period. Multivariable conditional logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Overall, cumulative airborne BaP exposure was significantly associated with the overall risk of BC, for each 1 interquartile range (IQR) increase in the concentration levels of BaP (1.42 ng/m3), the OR = 1.15 (95% CI: 1.04–1.27). However, by menopausal status, the significant positive association remained only in women who underwent menopausal transition (i.e. premenopausal women at inclusion who became postmenopausal at diagnosis), OR per 1 IQR = 1.20 (95% CI: 1.03–1.40). By hormone receptor status, positive associations were observed for ER+, PR + and ER + PR + BC, with ORs = 1.17 (95% CI: 1.04–1.32), 1.16 (95% CI: 1.01–1.33), and 1.17 (95% CI: 1.01–1.36) per 1 IQR, respectively. There was also a borderline positive association between BaP and grade 3 BC (OR per 1 IQR = 1.15 (95% CI: 0.99–1.34). We provide evidence of increased risk of BC associated with cumulative BaP exposure, which varied according to menopausal status, hormone receptor status, and grade of differentiation of BC. Our results add further epidemiological evidence to the previous experimental studies suggesting the adverse effects of BaP. [ABSTRACT FROM AUTHOR]

In the case of hepatocellular carcinoma (HCC) samples, classification of differentiation is crucial for determining prognosis and treatment strategy decisions. However, a label‐free and automated classification system for HCC grading has not been yet developed. Hence, in this study, we demonstrate the fusion of multiphoton microscopy and a deep‐learning algorithm for classifying HCC differentiation to produce an innovative computer‐aided diagnostic method. Convolutional neural networks based on the VGG‐16 framework were trained using 217 combined two‐photon excitation fluorescence and second‐harmonic generation images; the resulting classification accuracy of the HCC differentiation grade was over 90%. Our results suggest that a combination of multiphoton microscopy and deep learning can realize label‐free, automated methods for various tissues, diseases and other related classification problems. [ABSTRACT FROM AUTHOR]

The annexin protein superfamily has been implicated in multiple physiological and pathological processes, including carcinogenesis. Altered expression of various annexins has frequently been observed and linked to the development and progression of various human malignancies. However, information is lacking on the expression and clinical significance of annexin A9 (ANXA9) and A10 (ANXA10) in head and neck squamous cell carcinomas (HNSCC). ANXA9 and ANXA10 expression was evaluated in a large cohort of 372 surgically treated HPV-negative HNSCC patients and correlated with the clinicopathologic parameters and disease outcomes. Down-regulation of ANXA9 expression was found in 42% of HNSCC tissue samples, compared to normal epithelia. ANXA9 expression in tumors was significantly associated with oropharyngeal location and histological differentiation grade (p < 0.001). In marked contrast, ANXA10 expression was absent in normal epithelium, but variably detected in the cytoplasm of cancer cells. Positive ANXA10 expression was found in 64% of tumors, and was significantly associated with differentiation grade (p < 0.001), being also more frequent in oropharyngeal tumors (p = 0.019). These results reveal that the expression of both ANXA9 and ANXA10 is frequently altered in HNSCC and associated to the tumor differentiation grade, suggesting that they could be implicated in the pathogenesis of these cancers. [ABSTRACT FROM AUTHOR]

Objective: To investigate the differences of gemstone spectral curve and CT value of gastric cancer with different pathological types and differentiation degrees. Methods: 91 cases of preoperative gemstone CT images with gastric cancer were collected, including 24 cases of mucinous carcinoma, 67 cases of non-mucinous carcinoma, 16 cases of signet ring cell carcinoma, 8 cases of mucinous adenocarcinoma, 32 cases of moderately differentiated adenocarcinoma and 35 cases of poorly differentiated adenocarcinoma. Gemstone CT spectral imaging was performed preoperatively, and the spectral curve of the lesion in venous phase was obtained by using GSI Viewer software, the slope of the curve was calculated, and 11 monoenergetic CT values of 40~140 keV (10 keV interval) were measured. The gemstone spectral curves and CT values of gastric cancer with different pathological types and differentiation degrees are compared. Results: The curve slopes of non-mucinous carcinoma, signet ring cell carcinoma and poorly differentiated adenocarcinoma were -1.92±0.53, -1.73±0.37 and -2.14±0.54, respectively. The absolute values were higher than those of mucinous carcinoma (-1.45±0.54), mucinous adenocarcinoma (-0.90±0.34) and moderately differentiated adenocarcinoma (-1.67±0.41), and the differences were all statistically significant ( P <0.05). There were significant differences in monoenergetic CT values between mucinous and non-mucinous carcinomas at 40-140 keV (all P <0.05). The former was lower than the latter in different degrees, and the lower the energy, the greater the difference was. There were significant differences in monoenergetic CT values between signet ring cell carcinoma and mucinous adenocarcinoma at 40-100 keV (all P <0.05); monoenergetic CT values between poorly differentiated adenocarcinoma and moderately differentiated adenocarcinoma at 40-90 keV showed statistically significant differences ( P <0.05). Conclusions: Gastric cancer with different pathological types and differentiation degrees have their characteristic spectral curves in venous phase, and the monoenergetic CT values are significantly different at low energy. The spectral curve of gemstone CT may be helpful to evaluate the pathological type and differentiation degree of gastric cancer before operation.

Background/aims: Owing to the lack of effective molecular markers to evaluate colon cancer differentiation grade, screening of effective molecular markers for the diagnosis and treatment of colon cancer is of great significance. This study is a screening study for molecular markers related to the differentiation of colon using the tissue-specific genes of colon., Methods: This study compared the expression profiles of colon cancer at various differentiation grades and screened the down-regulated genes associated with decreased differentiation. IL22RA1 gene was derived from the intersection of obtained gene and colon tissue-specific genes. We used DriverDB and The Human Protein Atlas to analyze the expression level of IL22RA1 in various tissue cells, also used Kaplan-Meier method to analyze the correlation between IL22RA1 and the survival of colon cancer patients, and then used the ROC curve to analyze the specificity and sensitivity of IL22RA1 diagnosis of differentiated colon cancer., Results: We found that IL22RA1 gene expression was progressively down-regulated in high-differentiated, moderate-differentiated, low-differentiated, and undifferentiated colon cancer tissues. Both RNA and protein levels of IL22RA1 were higher in colon tissues and colon cancer tissues than in other normal and cancer tissues. Comparison of IL22RA1 expression in different cancer cells found that IL22RA1 expression was significantly higher in CACO-2 colon cancer cells than in other cancer cells. Survival analysis showed that IL22RA1 gene expression was positively correlated with the overall survival rate of colon cancer patients (P=0.0224). ROC curve analysis revealed that IL22RA1 expression had good specificity and sensitivity to stage II colon cancer., Conclusion: These findings suggest that IL22RA1 serves as a specific molecular marker for the differentiation of colon cancer., (© 2018 The Author(s). Published by S. Karger AG, Basel.)