Circulating free insulin-like growth factor-I and prostate cancer: a case-control study nested in the European prospective investigation into cancer and nutrition.

BACKGROUND: Circulating total insulin-like growth factor-I (IGF-I) is an established risk factor for prostate cancer. However, only a small proportion of circulating IGF-I is free or readily dissociable from IGF-binding proteins (its bioavailable form), and few studies have investigated the association of circulating free IGF-I with prostate cancer risk. METHODS: We analyzed data from 767 prostate cancer cases and 767 matched controls nested within the European Prospective Investigation into Cancer and Nutrition cohort, with an average of 14-years (interquartile range = 2.9) follow-up. Matching variables were study center, length of follow-up, age, and time of day and fasting duration at blood collection. Circulating free IGF-I concentration was measured in serum samples collected at recruitment visit (mean age 55 years old; standard deviation = 7.1) using an enzyme-linked immunosorbent assay (ELISA). Conditional logistic regressions were performed to examine the associations of free IGF-I with risk of prostate cancer overall and subdivided by time to diagnosis (≤ 14 and > 14 years), and tumor characteristics. RESULTS: Circulating free IGF-I concentrations (in fourths and as a continuous variable) were not associated with prostate cancer risk overall (odds ratio [OR] = 1.00 per 0.1 nmol/L increment, 95% CI: 0.99, 1.02) or by time to diagnosis, or with prostate cancer subtypes, including tumor stage and histological grade. CONCLUSIONS: Estimated circulating free IGF-I was not associated with prostate cancer risk. Further research may consider other assay methods that estimate bioavailable IGF-I to provide more insight into the well-substantiated association between circulating total IGF-I and subsequent prostate cancer risk.

The effects of ANRIL polymorphisms on colorectal cancer, tumor stage, and tumor grade among Iranian population.

BACKGROUND: Colorectal cancer (CRC) is a type of neoplasm, developing in the colon or rectum. The exact etiology of CRC is not well known, but the role of genetic, epigenetic, and environmental factors are established in its pathogenesis. Therefore, the aim of this research was to explore the effects of ANRIL polymorphisms on the CRC and its clinical findings. METHODS AND RESULTS: The peripheral blood specimens were collected from 142 CRC patients and 225 controls referred to Milad Hospital, Tehran, Iran. PCR- RFLP method was used to analyze ANRIL rs1333040, rs10757274 rs4977574, and rs1333048 polymorphisms. The ANRIL rs1333040 polymorphism was related to a higher risk of CRC in the co-dominant, dominant, and log-additive models. ANRIL rs10757274, rs4977574, and rs1333048 polymorphisms showed no effect on CRC susceptibility. The CGAA and TGGA haplotypes of ANRIL rs1333040/ rs10757274/ rs4977574/rs1333048 polymorphisms were associated with the higher and the lower risk of CRC respectively. The rs1333040 polymorphism was associated with higher TNM stages (III and IV). The frequency of ANRIL rs10757274 polymorphism was lower in CRC patients over 50 years of age only in the dominant model. In addition, the rs10757274 was associated with well differentiation in CRC patients. CONCLUSION: The ANRIL rs1333040 polymorphism was associated with a higher risk of CRC and higher TNM stages. ANRIL rs10757274 polymorphism was associated with the well-differentiated tumor in CRC.

The interrelationship between obesity and race in breast cancer prognosis: a prospective cohort study.

BACKGROUND: Obesity is associated with an increased breast cancer risk in postmenopausal women and may contribute to worse outcomes. Black women experience higher obesity and breast cancer mortality rates than non-Black women. We examined associations between race, obesity, and clinical tumor stage with breast cancer prognosis. METHODS: We conducted a prospective cohort study in 1,110 breast cancer patients, using univariable and multivariable Cox regression analyses to evaluate the effects of obesity, race/ethnicity, and clinical tumor stage on progression-free and overall survival (PFS and OS). RESULTS: 22% of participants were Black, 64% were Hispanic White, and 14% were non-Hispanic White or another race. 39% of participants were obese (body mass index [BMI] ≥ 30 kg/m2). In univariable analyses, tumor stage III-IV was associated with worse PFS and OS compared to tumor stage 0-II (hazard ratio [HR] = 4.68, 95% confidence interval [CI] = 3.52-6.22 for PFS and HR = 5.92, 95% CI = 4.00-8.77 for OS). Multivariable analysis revealed an association between Black race and worse PFS in obese (HR = 2.19, 95% CI = 1.06-4.51) and non-obese (HR = 2.11, 95% CI = 1.05-4.21) women with tumors staged 0-II. Obesity alone was not associated with worse PFS or OS. CONCLUSIONS: Results suggest a complex interrelationship between obesity and race in breast cancer prognosis. The association between the Black race and worse PFS in tumor stages 0-II underscores the importance of early intervention in this group. Future studies are warranted to evaluate whether alternative measures of body composition and biomarkers are better prognostic indicators than BMI among Black breast cancer survivors.

Lipid Metabolism-Related Gene Markers Used for Prediction Prognosis, Immune Microenvironment, and Tumor Stage of Pancreatic Cancer.

Recently, more and more evidence shows that lipid metabolism disorder has been observed in tumor, which impacts tumor cell proliferation, survival, invasion, metastasis, and response to the tumor microenvironment (TME) and tumor treatment. However, hitherto there has not been sufficient research to demonstrate the role of lipid metabolism in pancreatic cancer. This study contrives to get an insight into the relationship between the characteristics of lipid metabolism and pancreatic cancer. We collected samples of patients with pancreatic cancer from the Gene Expression Omnibus (GEO), the Therapeutically Applicable Research to Generate Effective Treatments (TARGET), and the International Cancer Genome Consortium (ICGC) databases. Firstly, we implemented univariate regression analysis to get prognosis-related lipid metabolism genes screened and a construction of protein-protein interaction (PPI) network ensued. Then, contingent on our screening results, we explored the molecular subtypes mediated by lipid metabolism-related genes and the correlated TME cell infiltration. Additionally, we studied the disparately expressed genes among disparate lipid metabolism subtypes and established a scoring model of lipid metabolism-related characteristics using the least absolute shrinkage and selection operator (LASSO) regression analysis. At last, we explored the relationship between the scoring model and disease prognosis, tumor stage, tumor microenvironment, and immunotherapy. Two subtypes, C1 and C2, were identified, and lipid metabolism-related genes were studied. The result indicated that the patients with subtype C2 have a significantly lower survival rate than that of the patients with subtype C1, and we found difference in abundance of different immune-infiltrating cells. The gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses revealed the association of these differentially expressed genes with functions and pathways related to lipid metabolism. Finally, we established a scoring model of lipid metabolism-related characteristics based on the disparately expressed genes. The results show that our scoring model have a substantial effect on forecasting the prognosis of patients with pancreatic cancer. The lipid metabolism model is an important biomarker of pancreatic cancer. Using the model, the relationship between disease prognosis, molecular subtypes, TME cell infiltration characteristics, and immunotherapy in pancreatic cancer patients could be explored.

Retrospective Evaluation of the Efficacy of Total Neoadjuvant Therapy and Chemoradiotherapy Neoadjuvant Treatment in Relation to Surgery in Patients with Rectal Cancer.

Background and Objective: In the therapeutic strategy of rectal cancer, radiotherapy has consolidated its important position and frequent use in current practice due to its indications as neoadjuvant, adjuvant, definitive, or palliative treatment. In recent years, total neoadjuvant therapy (TNT) has been established as the preferred regimen compared to concurrent neoadjuvant chemoradiotherapy (CRT). In relation to better outcomes, the percentage of patients who achieved pathological complete response (pCR) after neoadjuvant treatment is higher in the case of TNT. This study aimed to analyze the response to TNT compared to neoadjuvant CRT regarding pCR rate and the change in staging after surgical intervention. Materials and Methods: We performed a retrospective study on 323 patients with rectal cancer and finally analyzed the data of 201 patients with neoadjuvant treatment, selected based on the inclusion and exclusion criteria. Patients received CRT neoadjuvant therapy or TNT neoadjuvant therapy with FOLFOX or CAPEOX. Results: Out of 157 patients who underwent TNT treatment, 19.74% had pathological complete response, whereas in the group with CRT (n = 44), those with pCR were 13.64%. After neoadjuvant treatment, the most frequent TNM classifications were ypT2 (40.30%) and ypN0 (79.10%). The statistical analysis of the postoperative disease stage, after neoadjuvant therapy, showed that the most frequent changes were downstaging (71.14%) and complete response (18.41%). Only four patients (1.99%) had an upstaging change. The majority of patients (88.56%) initially presented clinical evidence of nodal involvement whereas only 20.9% of the patients still presented regional disease at the time of surgical intervention. Conclusions: By using TNT, a higher rate of stage reduction is obtained compared to the neoadjuvant CRT treatment. The post-neoadjuvant-treatment imagistic evaluation fails to accurately evaluate the response. A better response to TNT was observed in young patients.

Combining perineural invasion with staging improve the prognostic accuracy in colorectal cancer: a retrospective cohort study.

BACKGROUND: Current guidelines only propose the importance of perineural invasion(PNI) on prognosis in stage II colon cancer. However, the prognostic value of PNI in other stages of colorectal cancer (CRC) is ambiguous. METHODS: This single-center retrospective cohort study included 3485 CRC patients who underwent primary colorectal resection between January 2013 and December 2016 at the Sixth Affiliated Hospital of Sun Yat-sen University. Associations of PNI with overall survival (OS) and disease-free survival (DFS) were evaluated using multivariable Cox proportional hazards regression models. In addition, interaction analyses were performed to explore the prognostic effects of PNI in different clinical subgroups. RESULTS: After median follow-up of 61.9 months, we found PNI was associated with poorer OS (adjusted hazard ratio [aHR], 1.290; 95% CI, 1.087-1.531) and DFS (aHR, 1.397; 95% CI, 1.207-1.617), irrespective of tumor stage. Interestingly, the weight of PNI was found second only to incomplete resection in the nomogram for risk factors of OS and DFS in stage II CRC patients. Moreover, OS and DFS were insignificantly different between stage II patients with PNI and stage III patients (both P > 0.05). PNI was found to be an independent prognostic factor of DFS in stage III CRC (aHR: 1.514; 95% CI, 1.211-1.892) as well. Finally, the adverse effect of PNI on OS was more significant in female, early-onset, and diabetes-negative patients than in their counterparts (interaction P = 0.0213, 0.0280, and 0.0186, respectively). CONCLUSION: PNI was an important prognostic factor in CRC, more than in stage II. The survival of patients with stage II combined with perineural invasion is similar with those with stage III. PNI in stage III CRC also suggests a worse survival.

Pre-treatment quality of life in patients with salivary gland cancer in comparison with those of head and neck cancer patients.

INTRODUCTION: Salivary gland cancer (SGC) is a rare malignant tumor arising from the salivary glands, with a variety of clinical and biological behaviors different from head and neck cancer (HNC). Because of the rarity of SGC, there are limited data on pre-treatment quality of life (QoL). Therefore, we evaluated the pre-treatment QoL in SGC patients by stage and compared it with that of HNC patients. METHODS: From a prospective registry of HNC patients (2016-2020), we selected 225 patients with SGC, and 912 patients with oral cavity (OC) and oropharyngeal cancer (OPC) who were diagnosed in the same period as the HNC control group. The European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) and HNC-Specific Module (H&N35) were used to assess QoL. RESULTS: SGC patients had a statistically better baseline QoL (69.8 vs. 64.0), emotional (82.1 vs. 78.8), cognitive (92.0 vs. 88.7), and social function (86.3 vs. 80.5), and fewer symptoms than HNC patients. The estimated average QoL differences between SGC patient diagnosed at stages I and IV was -12.9. Especially, advanced-stage of tumors was associated with much lower role functioning and emotional functioning scores in SGC patients, compared to those in HNC patients, among females and of younger age. DISCUSSION: Although the overall QoL score was higher in SGC patients than in HNC patients, specific domains were significantly affected in SGC patients according to the tumor stage. Females and those of younger age were more affected by severity of disease in SGC. STUDY REGISTRATION: ClinicalTrials.gov Identifier NCT02546895.

Prognostic Worth of Nrf2/BACH1/HO-1 Protein Expression in the Development of Breast Cancer.

OBJECTIVES: Nrf2/BACH1/HO-1 proteins have been implicated in the development and progression of tumors. However, their clinical relevance in breast cancer remains unclear and understudied. This study evaluated Nrf2/BACH1/HO-1 protein expression and its relationship with age, tumor grade, tumor stage, TNM, ER, PR, HER2, and histologic type. METHODS: 114 female breast cancer and 30 noncancerous tissues were evaluated for Nrf2/BACH1/HO-1 protein expression using immunohistochemistry and Western blot. The relationships between the expression and clinicopathologic factors were assessed using the χ2 test. RESULTS: 74% of the cancerous samples had high Nrf2 protein expression, and 26% of them had low Nrf2 protein expression. Regarding the non-cancer samples, 43% had high Nrf2 protein expression and 57% had low Nrf2 protein expression (p < 0.002). 39% of the cancerous samples had high BACH1 protein expression, and 61% had low BACH1 protein expression. For the non-cancer samples, 80% had high BACH1 protein expression and 20% had low BACH1 protein expression (p < 0.031). 67% of the cancerous samples had high HO-1 protein expression, and 33% had low HO-1 protein expression. However, for the non-cancer samples, 17% of them had high HO-1 protein expression and 83% had low HO-1 protein expression (p < 0.001). The expression of Nrf2 and HO-1 significantly correlated with tumor grade, while BACH1 was significantly associated with tumor stage (p < 0.05). CONCLUSION: Nrf2, BACH1, and HO-1 could be explored as a biomarker for cancer stage, progression, and prognosis.

Oral Squamous Cell Carcinoma Clinico-pathological features in relation to Tumor Stage; AJCC 2018 perspective.

Objective: To investigate the association between clinicopathological findings and tumor stage according to AJCC 2018 guidelines in patients suffering from Oral squamous cell carcinoma (OSCC). Methods: A descriptive study was conducted from January 2019 to January 2020 at King Edward Medical University and University of Health Sciences on a total of 49 patients enrolled after obtaining written informed consent. Clinical and radiographic findings were recorded. Pathological reporting was done using AJCC 2018 cancer staging guidelines. Association between clinicopathological features with tumor stage and grade was assessed using Chi-square and Kruskal-Wallis test. Result: Mean age of the patients was 46.1 ± 10.6 years. Most of the tumors were of well differentiated type (49%) and moderately differentiated (40.8%) with predominant clinical stage III in 42.9% & IV in 44.9 % and primary tumor stage pT2 28.6% & pT3 36.7%. Significant difference was seen for primary tumor stage in relation to age, gender, depth of invasion, primary site, and size of tumor (p < 0.01). For clinical stages, significant difference was observed in the age, gender, size of tumor, nodal metastasis, and anatomical tumor site (p < 0.01). Conclusion: Application of 8th Edition AJCC guidelines identifies the importance of the latest classification with strong association of latest stage criteria with age, gender, site of primary tumor, tumor thickness, depth of invasion, nodal metastasis and size of largest lymph node involved, and Level of Lymph node involved (level III & V) in a subset of patients from a developing country.

MCAM abnormal expression and clinical outcome associations are highly cancer dependent as revealed through pan-cancer analysis.

MCAM (CD146) is a cell surface adhesion molecule that has been reported to promote cancer development, progression and metastasis and is considered as a potential tumor biomarker and therapeutic target. However, inconsistent reports exist, and its clinical value is yet to be confirmed. Here we took advantage of several large genomic data collections (Genotype-Tissue Expression, The Cancer Genome Atlas and Cancer Cell Line Encyclopedia) and comprehensively analyzed MCAM expression in thousands of normal and cancer samples and cell lines along with their clinical phenotypes and drug response information. Our results show that MCAM is very highly expressed in large vessel tissues while majority of tissues have low or minimal expression. Its expression is dramatically increased in a few tumors but significantly decreased in most other tumors relative to their pairing normal tissues. Increased MCAM expression is associated with a higher tumor stage and worse patient survival for some less common tumors but not for major ones. Higher MCAM expression in primary tumors may be complicated by tumor-associated or normal stromal blood vessels yet its significance may differ from the one from cancer cells. MCAM expression is weakly associated with the response to a few small molecular drugs and the association with targeted anti-BRAF agents suggests its involvement in that pathway which warrants further investigation.

Pre-diagnostic faecal calprotectin levels in patients with colorectal cancer: a retrospective study.

BACKGROUND: Faecal calprotectin (FC) is a potential biomarker for colorectal cancer (CRC) screening. There is uncertainty if tumor characteristics are associated with FC levels. We investigated how tumor stage and tumor localization influence the extent of FC levels in patients with CRC in clinical practice. METHODS: In two cohorts of patients with CRC, we retrospectively analyzed FC tests (CALPRO®) performed within three months prior to diagnosis. One hundred twenty-four patients with CRC were included (mean age 68 years, 44% women). RESULTS: Ninety-eight patients with CRC (79%) had a FC ≥ 50 µg/g. FC correlated positively with tumor stage (UICC based on WHO TNM classification) (rs 0.24; p = 0.007) and with CRP levels (rs 0.31, p = 001), and a negatively with B-haemoglobin (rs -0.21; p = 0.019). The patients with right-sided CRC had significantly more often a FC ≥ 50 µg/g than patients with left-sided CRC (92% vs 74% p = 0.027). In a binary logistic regression analysis, tumor stage III/IV (adjusted OR 3.47; CI 1.27-9.42) and right-sided tumor localization (adjusted OR 3.80; CI 1.01-14.3) were associated with FC ≥ 50 µg/g. Tumor stage III/IV (adjusted OR 2.30; CI 1.04-5.10) and acetylsalicylic use (adjusted OR 3.54; CI 1.03-12.2) were associated with FC ≥ 100 µg/g. In a cox regression analysis, a FC ≥ 100 µg/g was not associated with survival (Hazard OR 0.61; CI 0.24-1.52). CONCLUSIONS: Elevated pre-diagnostic FC levels were common in patients with CRC in close proximity to diagnosis. Right-sided localization and tumor stage were significantly associated with a rise in FC levels.

Is laterality in breast Cancer still worth studying? Local experience in Bahrain.

BACKGROUND: Laterality in breast cancer means an increased frequency of left-sided breast cancers compared to right-sided breast cancers ranging between 1.05 and 1.26. It was first described in 1935 by Fellenberg, Sweden. The explanation of this phenomenon is not clear, but the association with other factors was found. This study aimed to explore the laterality of breast cancer in Bahrain as a model for Arabian countries. The association of laterality with the clinicopathological characteristics of the tumor was also analyzed to explore any applied clinical value. METHODS: This is a cross-sectional, retrospective review of a particular ethnic population to study laterality of breast cancer versus a number of clinicopathological factors, as well as prognosis. The study analyzed 228 breast cancer patients treated in Arabian Gulf University facilities in Bahrain between 1999 and 2020. Three bilateral breast cancer and two malignant phyllodes patients were excluded. The following variables were analyzed: laterality ratio (Lt/Rt) and the association between laterality and clinicopathological characteristics (age at diagnosis, family history of malignancy, size of the tumor, tumor grade, histological type, hormonal receptors and HER2, axillary lymph node status, tumor stage, five-year survival rate, nulliparity, and multifocality). RESULTS: The laterality ratio (Lt/Rt) was 1.06 and was 0.97 for patients below 50 years of age, and 1.19 for patients 50 years of age and above. Analysis of our data showed a statistically significant association between laterality and tumor stage (p. value =0.025) at presentation, and laterality and family history of malignancy (p. value =0.052). Right-sided breast cancer was associated with a higher positive family history of malignancy and an increased ratio of locally advanced and metastatic disease, and a reduced 5-year survival in relation to size and stage. Left-sided breast cancer was associated with higher early tumor stage. CONCLUSION: This is the first study exploring the issue of breast cancer laterality in a defined Arabian population. The laterality ratio in this study was 1.06, which is consistent with the globally published range (1.05 to 1.26) and is increasing with increasing age. The association between breast cancer laterality, and the hormonal and HER2 is still not widely addressed in the available literature, although other clinicopathological characteristics were extensively analyzed.

Pathologic primary tumor factors associated with risk of lymph node involvement in patients with non-endometrioid endometrial cancer.

PURPOSE/OBJECTIVES: Lymph node (LN) involvement is an important factor in guiding adjuvant treatment for patients with endometrial cancer. Risk factors for LN involvement are fairly well-established for endometrial adenocarcinoma, but it is not as well defined whether these factors similarly predict LN positivity in less common histologies. MATERIALS/METHODS: Patients diagnosed with pathologic T1-T2 carcinosarcoma, clear cell, uterine papillary serous carcinoma (UPSC), and mixed histologic type endometrial cancer between 2004 and 2016 undergoing primary surgery with at least 1 lymph node sampled in the National Cancer Data Base were identified. Logistic regression was performed to identify primary pathologic tumor predictors of LN positivity. Nomograms were created to predict overall, pelvic only, and paraaortic with or without pelvic LN involvement. RESULTS: Among 11,390 patients included, 1950 (18%) were node positive. On multivariable analysis, increasing pathologic tumor stage (pT2 versus pT1a, odds ratio [OR] 3.63, 95% confidence interval [CI] 3.15-4.18, p < 0.001), increase in tumor size per centimeter (OR 1.08, 95% CI 1.06-1.10, p < 0.001), and the presence of lymphovascular invasion (LVI) (OR 4.97, 95% CI 4.43-5.57, p < 0.001) were predictive of overall LN positivity. Relative to carcinosarcoma, both clear cell (OR 1.54, 95% CI 1.22-1.95, p < 0.001) and UPSC (OR 1.73, 95% CI 1.48-2.02, p < 0.001) histology were significantly associated with a higher risk of LN positivity while mixed histology was not (OR 1.07, 95% CI 0.92-1.24, p = 0.42). CONCLUSION: Among patients with non-endometrioid endometrial cancer, predictors of LN positivity are similar to endometrial adenocarcinoma. The nomograms provided could be helpful in making adjuvant treatment decisions for these less common histologies.

Association of dipeptidyl peptidase IV polymorphism with clinicopathological characters of oral cancer.

OBJECTIVE: To evaluate the associations between dipeptidyl peptidase IV (DPP4) single-nucleotide polymorphism (SNP) and clinicopathological characteristics of oral cancer. METHODS: Four loci of DPP4 SNPs (rs7608798 A/G, rs3788979 C/T, rs2268889 T/C, and rs6741949 G/C) were genotyped by using the TaqMan allelic discrimination in 1238 oral cancers patients and 1197 non-cancer individuals. RESULTS: The percentage of DPP4 SNP rs2268889 TC + CC was significantly higher in the oral cancer participants compared to the control group (odds ratio [OR]: 1.178, 95% confidence interval (CI): 1.004-1.382, p = 0.045). Among 1676 smokers, DPP4 polymorphisms carriers with betel quid chewing were found to have an 8.785- to 10.903-fold risk to have oral cancer compared to DPP4 wild-type carriers without betel quid chewing. Similar trend was found in individuals with alcohol consumption. Moreover, the oral cancer individuals without cigarette smoking history with at least one varied C allele of DPP4 rs2268889 had a significantly higher percentage of large tumor size with the wild-type TT homozygote (p = 0.011). CONCLUSIONS: The DPP4 SNP may correlate to the development of oral cancer in those with cigarette smoking and alcohol consumption. Besides, the DPP4 SNP rs2268889 could relate to worse clinical course of oral cancer in non-smokers.

Characteristics of gastric cancer gut microbiome according to tumor stage and age segmentation.

With the development of 16S rRNA technology, gut microbiome evaluation has been performed in many diseases, including gastrointestinal tumors. Among these cancers, gastric cancer (GC) exhibits high morbidity and mortality and has been extensively studied in its pathogenesis and diagnosis techniques. The current researches have proved that the gut microbiome may have the potential to distinguish GC patients from healthy patients. However, the change of the gut microbiome according to tumor node metastasis classification (TNM) has not been clarified. Besides, the characteristics of gut microbiome in GC patients and their ages of onset are also ambiguous. To address the above shortcomings, we investigated 226 fecal samples and divided them according to their tumor stage and onset age. The findings revealed that surgery and tumor stage can change the characteristic of GC patients' gut microbiota. In specific, the effect of surgery on early gastric cancer (EGC) was greater than that on advanced gastric cancer (AGC), and the comparison of postoperative microflora with healthy people indicated that EGC has more differential bacteria than AGC. Besides, we found that Collinsella, Blautia, Anaerostipes, Dorea, and Lachnospiraceae_ND3007_group expressed differently between EGC and AGC. More importantly, it is the first time revealed that the composition of gut microbiota in GC is different between different onset ages. KEY POINTS: •Gut microbiota of gastric cancer (GC) patients are either highly associated with TNM stage and surgery or not. It shows surgery has more significant changes in early gastric cancer (EGC) than advanced gastric cancer (AGC). •There existed specific gut microbiota between EGC and AGC which may have potential to distinguish the early or advanced GC. •Onset age of GC may influence the gut microbiota: the composition of gut microbiota of early-onset gastric cancer (EOGC) and late-onset gastric cancer (LOGC) is significantly different.

Ethnic disparities in colorectal cancer outcomes: a population study from Israel.

Objectives: Colorectal cancer (CRC) is an important cause of morbidity and mortality worldwide. Clear ethnic disparities in the incidence of CRC and its outcomes have been observed globally, but only few research efforts have been invested so far in the unique ethnic scene of Israeli population. This study aims to compare the clinico-pathologic features, tumor's characteristics and prognosis between Arab and Jewish CRC patients as well as among Jewish subgroups living within the same central coastal region in Israel.Methods: In this retrospective, single center study, a total of 401 patients with pathologically confirmed CRCs diagnosed during the years 2008-2015 were included. These were divided into Jewish (n = 334) and Arab (n = 67) groups. Data collected included demographics, country of birth, clinical presentation and family history. Tumor stage, location, histologic grade and mortality rate were compared retrospectively between both groups and within Jewish sub-populations.Results: Arabs were significantly younger at diagnosis (62.7 ± 12.9 vs. 69.3 ± 13.01; P < 0.01), presented more frequently with rectal bleeding, and were less likely to be diagnosed due to positive fecal occult blood test (9% vs. 22.6%; P = 0.012). Tumor distribution through the colon was comparable between both groups and characterized by a distal predominance. Arabs had a significantly higher rate of advanced stage at diagnosis (58% vs. 50.5%, OR = 2.454, 95%CI = 1.201-5.013; P = 0.02) when compared to Jews. Mortality rates were comparable between both groups. In the Jewish subpopulation analysis, we found that immigrants, especially those born in the former USSR, presented with significantly advanced tumor stages when compared to native Israelis (55% vs. 37.5%; P = 0.02).Conclusion: CRC in two major ethnic populations in Israel, Arabs and Jews, varied in terms of age at diagnosis, clinical presentation and stage at diagnosis. Similar findings were documented within a non-native Jewish subpopulation, raising the possibility of a low utilization of screening programs in these groups.

Prognostic predictors in recurrent adult granulosa cell tumors of the ovary: a systematic review and meta-analysis.

BACKGROUND: Ovarian adult granulosa cell tumours are low-grade malignant sex cord-stromal neoplasm with a low recurrence rate. Prognostic factors for recurrence include tumor stage, tumor rupture in Stage I neoplasms and the presence of residual tumors after surgery. However, in recurrent tumors, prognostic factors for overall survival (OS) are lacking. In the present paper, we conducted a systematic meta-analysis with the aim to assess prognostic factors for OS in patients with recurrent GCT. METHODS: Electronic databases were searched for all studies assessing prognostic factors in recurrent adult granulosa cell tumor of the ovary. Student T test, Fisher's exact test and Kaplan-Meier survival analysis with long-rank test were used to assess differences among groups; a p value < 0.05 was considered significant. RESULTS: Eleven studies analyzing 102 recurrent tumors were included in the systematic review. Tumor stage and localization of recurrent tumors were significantly associated with OS on Kaplan-Meier analysis; Cox regression analysis showed a HR of 0.879 for the stage II, of 3.052 for the stage III, and of 2.734 for stage IV tumor was significantly associated with OS (p = 0.037); observed HRs for abdominal and thoracic locations were of 2.405 and of 4.024, respectively. CONCLUSIONS: In conclusion, the present article emphasizes the prognostic significance of tumor stage > II and extrapelvic anatomic sites of recurrences in patients with recurrent granuolase cell tumors of the ovary.

Histological Grade and Tumor Stage Are Correlated with Expression of Receptor Activator of Nuclear Factor Kappa b (Rank) in Epithelial Ovarian Cancers.

The receptor activator of nuclear factor kappa B (RANK) is becoming recognized as a master regulator of tumorigenesis, yet its role in gynecological cancers remains mostly unexplored. We investigated whether there is a gradation of RANK protein and mRNA expression in epithelial ovarian cancer (EOC) according to malignancy and tumor staging. Immunohistochemical expression of RANK was examined in a cohort of 135 (benign n = 29, borderline n= 23 and malignant n = 83) EOCs. Wild type and truncated RANK mRNA isoform quantification was performed in a cohort of 168 (benign n = 26, borderline n = 13 and malignant n = 129) EOCs. RANK protein and mRNA values were increased in malignant vs. benign or borderline conditions across serous, mucinous and endometrioid cancer subtypes. Additionally, a trend of increased RANK values with staging was observed for the mucinous and serous histotype. Thus, increased expression of RANK appears associated with the evolution of disease to the onset of malignancy in EOC. Moreover, in some EOC histotypes, RANK expression is additionally associated with clinicopathological markers of tumor aggressiveness, suggesting a role in further progression of tumor activity.

Clinicopathological correlation of radiologic measurement of post-therapy tumor size and tumor volume for pancreatic ductal adenocarcinoma.

OBJECTIVES: Tumor size measurement is critical for accurate tumor staging in patients with pancreatic ductal adenocarcinoma (PDAC). However, accurate tumor size measurement is challenging in patients who received neoadjuvant therapy before resection, due to treatment-induced fibrosis and tumor invasion beyond the grossly identified tumor area. In this study, we evaluated the correlation between the tumor size and tumor volume measured on post-therapy computed tomography (CT) scans and the pathological measurement. Also, we investigated the correlation between these measurements and clinicopathological parameters and survival. MATERIALS AND METHODS: Retrospectively, we evaluated 343 patients with PDAC who received neoadjuvant therapy, followed by pancreaticoduodenectomy and had pre-operative pancreatic protocol CT imaging. We measured the longest tumor diameter (RadL) and the radiological tumor volume (RadV) on the post-therapy CT scan, then we categorized RadL into four radiologic tumor stages (RTS) based on the current AJCC staging (8th edition) protocol and RadV based on the median. Pearson correlation or Spearman's coefficient (δ), T-test and ANOVA was used to test the correlation between the radiological and pathological measurement. Chi-square analysis was used to test the correlation with the tumor pathological response, lymph-node metastasis and margin status and Kaplan-Meier and Cox-proportional hazard for survival analysis. P-value < 0.05 was considered significant. RESULTS: As a continuous variable, RadL showed a positive linear correlation with the post-therapy pathologic tumor size in the overall patient population (Pearson correlation coefficient: 0.72, P < 0.001) and RadV (δ: 0.63, p < 0.0001). However, there was no correlation between RadL and pathologic tumor size in patients with ypT0 and those with pathologic tumor size of ≤1.0 cm. Post-therapy RTS and RadV group correlated with ypT stage, tumor response grades using either CAP or MDA grading system, distance of superior mesenteric artery margin and tumor recurrence/metastasis. CONCLUSION: Although RadL tends to understage ypT in PDAC patients who had no radiologically detectable tumor or small tumors (RTS0 or RTS1), radiologic measurement of post-therapy tumor size may be used as a marker for the pathologic tumor staging and tumor response to neoadjuvant therapy.

Impact of the suspension and restart of the Dutch breast cancer screening program on breast cancer incidence and stage during the COVID-19 pandemic.

The COVID-19 pandemic forced the Dutch national breast screening program to a halt in week 12, 2020. In week 26, the breast program was resumed at 40% capacity, which increased to 60% in week 34. We examined the impact of the suspension and restart of the screening program on the incidence of screen-detected and non-screen-detected breast cancer. We selected women aged 50-74, diagnosed during weeks 2-35 of 2018 (n = 7250), 2019 (n = 7302), or 2020 (n = 5306), from the Netherlands Cancer Registry. Weeks 2-35 were divided in seven periods, based on events occurring at the start of the COVID-19 pandemic. Incidence of screen-detected and non-screen-detected tumors was calculated overall and by age group, cT-stage, and cTNM-stage for each period in 2020, and compared to the incidence in the same period of 2018/2019 (averaged). The incidence of screen-detected tumors decreased during weeks 12-13, reached almost zero during weeks 14-25, and increased during weeks 26-35. Incidence of non-screen-detected tumors decreased to a lesser extent during weeks 12-16. The decrease in incidence was seen in all age groups and mainly occurred for cTis, cT1, DCIS, and stage I tumors. Due to the suspension of the breast cancer screening program, and the restart at reduced capacity, the incidence of screen-detected breast tumors decreased by 67% during weeks 9-35 2020, which equates to about 2000 potentially delayed breast cancer diagnoses. Up to August 2020 there was no indication of a shift towards higher stage breast cancers after restart of the screening.