Optimizing detection of clinically significant prostate cancer through nomograms incorporating mri, clinical features, and advanced serum biomarkers in biopsy naïve men.

PURPOSE: To develop nomograms that predict the detection of clinically significant prostate cancer (csPCa, defined as ≥GG2 [Grade Group 2]) at diagnostic biopsy based on multiparametric prostate MRI (mpMRI), serum biomarkers, and patient clinicodemographic features. MATERIALS AND METHODS: Nomograms were developed from a cohort of biopsy-naïve men presenting to our 11-hospital system with prostate specific antigen (PSA) of 2-20 ng/mL who underwent pre-biopsy mpMRI from March 2018-June 2021 (n = 1494). The outcomes were the presence of csPCa and high-grade prostate cancer (defined as ≥GG3 prostate cancer). Using significant variables on multivariable logistic regression, individual nomograms were developed for men with total PSA, % free PSA, or prostate health index (PHI) when available. The nomograms were both internally validated and evaluated in an independent cohort of 366 men presenting to our hospital system from July 2021-February 2022. RESULTS: 1031 of 1494 men (69%) underwent biopsy after initial evaluation with mpMRI, 493 (47.8%) of whom were found to have ≥GG2 PCa, and 271 (26.3%) were found to have ≥GG3 PCa. Age, race, highest PIRADS score, prostate health index when available, % free PSA when available, and PSA density were significant predictors of ≥GG2 and ≥GG3 PCa on multivariable analysis and were used for nomogram generation. Accuracy of nomograms in both the training cohort and independent cohort were high, with areas under the curves (AUC) of ≥0.885 in the training cohort and ≥0.896 in the independent validation cohort. In our independent validation cohort, our model for ≥GG2 prostate cancer with PHI saved 39.1% of biopsies (143/366) while only missing 0.8% of csPCa (1/124) with a biopsy threshold of 20% probability of csPCa. CONCLUSIONS: Here we developed nomograms combining serum testing and mpMRI to help clinicians risk stratify patients with elevated PSA of 2-20 ng/mL who are being considered for biopsy. Our nomograms are available at https://rossnm1.shinyapps.io/MynMRIskCalculator/ to aid with biopsy decisions.

Real-world use of MRI for risk stratification prior to prostate biopsy.

BACKGROUND: The utilization of MRI to risk stratify elevated PSA prior to prostate biopsy has been inconsistently adopted and varies considerably by practice setting. This study aims to evaluate the usage and performance of MRI as an advanced risk stratification tool of elevated PSA prior to biopsy and identify factors associated with differential utilization of MRI at a large academic setting with ready access to 3T multiparametric MRI of the prostate. METHODS: A retrospective single-center study of 2900 men presenting with elevated PSA 2-20 ng/mL from 2018 through 2021 was conducted. We analyzed trends in MRI utilization and outcomes of prostate biopsy by MRI usage. Univariate and multivariate logistic regressions were performed to calculate odds ratios to identify patient- and provider-level predictors of MRI usage. RESULTS: Rates of prebiopsy MRI utilization increased from 56% in 2018 to 89% in 2021 (p < 0.001). Prebiopsy MRI led to biopsy avoidance in 31% of men. MRI usage enhanced detection of clinically significant prostate cancer by 13% and reduced identification of Gleason Grade Group 1 disease by 3% and negative biopsies by 10% (p < 0.001). Men who received MRI were more likely to be younger than 75 years in age and have private or Medicare insurance, PSA >4 ng/mL, and PHI >27. In both univariate and multivariate analysis, black race and Medicaid insurance were associated with reduced MRI utilization (all p < 0.001). Urologic provider was an independent predictor of MRI usage (p < 0.001). CONCLUSIONS: Use of MRI as a risk stratification tool for elevated PSA rose during this 4-year study period. Men who self-identify as black or men with Medicaid coverage have diminished rates of MRI usage. Considerable provider-level variability in MRI use was observed. Future research aimed at identifying factors affecting implementation of MRI as a routine risk assessment tool is warranted.

Cervical cancer screening among Michigan women: 'The Special Cancer Behavioral Risk Factor Survey', 2004-2008.

The burden of cervical cancer remains greater among minority women. The purpose of this study was to evaluate racial/ethnic disparities in cervical cancer screening among minority women in Michigan. Data from 8,023 women (≥ 40 years) surveyed in the 2004-2008 Michigan Special Cancer Behavioral Risk Factor Survey were used to assess racial/ethnic differences in cervical cancer screening, knowledge and beliefs. Unexpectedly, African-American and Hispanic women reported being screened for cervical cancer at rates similar to, or higher than, Whites. Women demonstrated limited knowledge of cervical cancer risk factors and its signs/symptoms. Most minority women were more likely than Whites to believe in the importance of cervical screening, with Hispanic women more likely to support HPV vaccination. Differential utilisation of screening does not explain the disproportionately high rates of cervical cancer among minorities. Future research should examine disparities in the follow-up of abnormal cervical results and receipt of treatment.

Hepatitis C virus and other risk factors in hepatocellular carcinoma.

UNLABELLED: Hepatocellular carcinoma (HCC) increased in Egypt in the past years, becoming the most common cancer among men. Hepatitis B virus (HBV) and hepatitis C virus (HCV) are the known primary risk factors for HCC. This study describes the viral profile of HCC in a predominantly rural area in Egypt. We included 148 HCC cases and 148 controls from the Tanta Cancer Center and the Gharbiah Cancer Society in the Nile delta region. Serological (ELISA) and molecular (PCR) analysis for HBV and HCV infection were performed on plasma samples from each subject. Epidemiologic, environmental, and medical histories were collected by interviewing of subjects. Around 90.5% of cases and controls were from rural areas. HCV infection was high in both cases and controls (89.2% and 49.3%, for cases and controls respectively by serology). HCV was the most important HCC risk factor [OR 9.7 (95% CI: 3.3-28.0, P <0.01)], and HBV infection showed marginal tendency of increased risk [OR 5.4 (95% CI: 0.9-31.8, P <0.06)]. Ever worked in farming [OR 2.8 (95% CI: 1.1-7.2, P <0.03)] and history of cirrhosis [OR 3.6 (95% CI: 1.6-8.1, P <0.01)] or blood transfusion [OR 4.2 (95% CI: 0.99-17.8, P <0.05)] were also associated with increased HCC risk. This study in a predominantly rural area in Egypt supports previous reports from other parts of Egypt that HCV infection is the primary HCC risk factor in Egypt. Further understanding of the relationship between infection and other risk factors in the development of HCC could lead to targeted interventions for at-risk individuals. KEYWORDS: hepatocellular carcinoma; hepatitis; rural; risk factors; Egypt.

Geographic distribution of hematopoietic cancers in the Nile delta of Egypt.

BACKGROUND: Previous evidence indicated that incidence rates of non-Hodgkin's lymphoma (NHL) are high in Egypt although little is known about risk factors. MATERIALS AND METHODS: Using data from the population-based cancer registry of Gharbiah governorate in Egypt, we assessed the 1999-2005 incidence of hematopoietic cancers (HCs) based on the ICD-O3 by age- and sex-specific urban-rural distribution. RESULTS: NHL showed the highest incidence among all HCs (11.7 per 100 000). Urban incidence of HCs was higher than rural incidence. Incidence rates of Hodgkin's lymphoma (HL) and NHL were high especially among urban males up to the 64-year age category. Rural incidence of HL and NHL was high below age 20. Among the districts of the governorate, we observed NHL incidence pattern similar to that observed for hepatocellular carcinoma because of the possible link to hepatitis C virus for both cancers. Comparison to the published HCs data from Algeria, Cyprus, and Jordan showed the highest NHL rate in Egypt than the other countries in the region. CONCLUSIONS: Future studies should define the role of environmental exposures in hematopoietic carcinogenesis in this population. In-depth studies should also investigate the role of access to health care in the urban-rural variation of HC distribution in this population.

Urban-rural differences of gynaecological malignancies in Egypt (1999-2002).

OBJECTIVE: In previous studies, we have shown a three to four times higher urban incidence of breast cancer and estrogen receptor-positive breast cancers in the Gharbiah Province of Egypt. We investigated the urban-rural incidence differences of gynaecologic malignancies (uterine, ovarian and cervical cancers) to explore if they show the same trend that we found for breast cancer. DESIGN: Cancer registry-based incidence comparison. SETTING: Gharbiah population-based cancer registry (GPCR), Tanta, Egypt. SAMPLE: All patients with uterine, ovarian and cervical cancer in GPCR from 1999 to 2002. METHODS: We calculated uterine, ovarian and cervical cancer incidence from 1999 to 2002. For each of the three cancers, we calculated the overall and age-specific rates for the province as a whole, and by urban-rural status, as well as for the eight districts of the province. RESULTS: Incidence of all three cancer sites was higher in urban than in rural areas. Uterine cancer showed the highest urban-rural incidence rate ratio (IRR = 6.07, 95% CI = 4.17, 8.85). Uterine cancer also showed the highest urban incidence in the oldest age group (70+ age category, IRR = 14.39, 95% CI = 4.24, 48.87) and in developed districts (Tanta, IRR = 4.14, 95% CI = 0.41, 42.04). Incidence rates by groups of cancer sites showed an increasing gradient of urban incidence for cancers related to hormonal aetiology, mainly of the breast and uterus (IRR = 4.96, 95% CI = 2.86, 8.61). CONCLUSIONS: The higher urban incidence of uterine cancer, coupled with our previous findings of higher incidence of breast cancer and estrogen receptor positive breast cancer in urban areas in this region, may be suggestive of possible higher exposure to environmental estrogenic compounds, such as xenoestrogens, in urban areas.

Geographical clustering of pancreatic cancers in the Northeast Nile Delta region of Egypt.

The northeast Nile Delta, Egypt's most polluted region, appears to have a high incidence of pancreatic cancer. We sought to determine whether there is any geographic clustering of pancreatic cancers there and, if so, whether such clustering might be associated with environmental pollution. Using data from the medical records of the Gastrointestinal Surgical Center of Mansoura University in the Dakahleia Province of Egypt and detailed geographical maps of the northeast Nile Delta region, we plotted the residences of all 373 patients who had pancreatic cancer diagnosed between 1995 and 2000. The study region has 15 administrative districts, whose centroid coordinates, population, and number of pancreatic cancer patients were determined for this study. Monte Carlo simulation identified statistically significant clustering of pancreatic cancer in five subdivisions located near the Nile River and Delta plains. This clustering was independent of population size and formed two larger clusters. When data were analyzed by sex, clustering of pancreatic cancer was observed in the same five subdivisions for men but only two subdivisions showed clustering for women. Together, our data suggest that there is clustering of pancreatic cancer cases in the northeast Nile delta region and that this clustering may be related to water pollution. Our data also warrant future studies of the association between water pollution and pancreatic cancer in the region.

Contrasting molecular pathology of colorectal carcinoma in Egyptian and Western patients.

Colorectal carcinoma is uncommon in Egypt, but a high proportion of cases occurs before age 40 years and in the rectum. We compared the molecular pathology of 59 representative Egyptian patients aged 10-72 to Western patients with sporadic, young-onset, or hereditary non-polyposis colorectal cancer syndrome (HNPCC)-associated carcinoma and found significant differences. Most Egyptian cancers were rectal (51%) and poorly differentiated (58%). High levels of microsatellite instability (MSI-H) were frequent (37%) and attributable in some cases (36%) to methylation of the promoter of the hMLH1 mismatch repair gene, but no MSI-H cancer had loss of hMSH2 mismatch repair gene product of the type seen with germline hMSH2 mutation in HNPCC. K-ras mutation was uncommon (11%). In subset analyses, high frequencies of MSI-H in rectal carcinomas (36%) and p53 gene product overexpression in MSI-H cancers (50%) were found. MSI-H and K-ras mutation in Egyptians under age 40 were unusual (17% and 0%, respectively), and schistosomiasis was associated with MSI and K-ras mutation. Cluster analysis identified 2 groups: predominantly young men with poorly differentiated mucinous and signet-ring cell colorectal carcinoma lacking K-ras mutation; older patients who had well- or moderately differentiated adenocarcinoma often with MSI-H, K-ras mutation and schistosomiasis. Our findings show that the molecular pathology of colorectal cancer in older as well as younger Egyptians has unique differences from Western patients, and schistosomiasis influences the molecular pathogenesis of some tumours.

Planning cancer prevention strategies based on epidemiologic characteristics: an Egyptian example.

BACKGROUND AND METHODS: We describe the epidemiology, cancer prevention strategies, and educational messages to be learned from four characteristic cancers in Egypt: urinary bladder, liver, lung, and early-onset colorectal cancers. RESULTS: For bladder cancer, effective and convenient treatment of schistosomiasis, using social marketing and mass media in public and medical education has contributed dramatically to primary prevention of bladder cancer in Egypt. For liver cancer, educating hospital administrators to remove structural barriers to good practice may help the control of hepatitis transmission and related liver cancer. For lung cancer, the 50-year American experience for controlling tobacco smoking, beginning with physicians, could be very effective in Egypt and other countries with increasing smoking rates in the young so as to avert the expected epidemics of lung cancer. For colorectal cancer, more attention to physician and public education about the importance of interviewing colorectal cancer patients about a family history of cancer and the screening of at-risk families could be very effective in early detection of colorectal cancer. CONCLUSION: Countries with similar cancer epidemiology experience should make use of successful cancer prevention and education strategies that could be translated from the Egyptian experience.

Inheritance of the 194Trp and the 399Gln variant alleles of the DNA repair gene XRCC1 are associated with increased risk of early-onset colorectal carcinoma in Egypt.

Patients under age 40 constitute 35.6% of all colorectal cancer cases in Egypt, an unusual disease pattern to which both environmental exposures and inefficient DNA repair may contribute. While a number of polymorphisms in DNA repair genes have been recently identified, their role as cancer risk modifiers is yet to be determined. In a pilot case-control study, we tested the hypothesis that polymorphisms in the gene for the DNA repair enzyme XRCC1 are associated with increased risk of colorectal cancer among Egyptians. Using a multiplex polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methodology, allelic variants of the XRCC1 gene at codons 194 (Arg-->Trp) (194Trp) and 399 (Arg-->Gln) (399Gln), were analyzed in DNA from lymphocytes of 48 newly-diagnosed colorectal cancer cases and 48 age- and sex-matched controls. Overall, the inheritance of 194Trp allele (Arg/Trp genotype) and 399Gln allele (combined Arg/Gln and Gln/Gln genotypes) was associated with increased colorectal cancer risk (odds ratio (OR)=2.56, 95% confidence limits (CL) 0.73-9.40, and P=0. 08 for 194Trp allele and OR=3.98, 95% CL 1.50-10.6, and P<0.001 for 399Gln allele). Interestingly, the frequencies of 194Trp and 399Gln genotypes were higher in colorectal cancer cases under age 40 than in corresponding controls, and an association between both polymorphisms and early age of disease onset was observed (OR=3.33, 95% CL 0.48-35.90, and P=0.16 for 194Trp and OR=11.90, 95% CL 2.30-51.50, and P=0.0003 for 399Gln). Analysis of the data after adjustment for place of residence indicated that the frequencies of the genotypes with the 194Trp and the 399Gln alleles were higher among urban residents (OR=3.33, 95% CL 0.48-35.90, and P=0.16 for 194Trp and OR=9.97, 95% CL 1.98-43.76, and P<0.001 for 399Gln) than among rural residents (OR=2.00, 95% CL 0.36-26.00, and P=0.30 for 194Trp and OR=1.90, 95% CL 0.50-7.53, and P=0.20 for 399Gln). These findings support our hypothesis and suggest that polymorphisms in the XRCC1 gene, in conjunction with place of residence, may modify disease risk. This first demonstration that polymorphisms in DNA repair genes may contribute to colorectal cancer susceptibility and may increase the risk of early onset of the disease opens the door for future studies in that direction.

Study of some biological markers of stress in nail industry.

The aim of this study was to investigate the different markers of stress in nail industry. Blood and urine biological samples were collected from 30 exposed workers and 30 age and sex matched control subjects from the administrative department of the same factory. The total antioxidant activity (Dmax) and lipid peroxidation was analyzed in blood. The level of catecholamines in the urine was also determined The median level of Dmaxwas significantly lower in the exposed workers (87.12) compared with that of the control (115.85) (p < 0.01). Also the level of lipid peroxidation was significantly lower in the exposed workers (44.5) compared with that of the control (74.0) (p < 0.01). The median level of urinary catecholamines was significantly higher in the exposed workers (295) compared with that of controls (37.5). Attention should be paid to the necessity of the application of the different biological markers of stress in different sectors of industry especially in nail industry.

Cancer mortality in Menofeia, Egypt: comparison with US mortality rates.

OBJECTIVES: In developing countries where cancer registries are unavailable, mortality statistics from death certification may be a practical source of cancer statistics. We aimed at describing the cancer mortality in Egypt and comparing it to that in the US. METHODS: We used the mandatory and routinely available mortality records of Menofeia province in the Nile Delta region of Egypt, which is typical of the rest of Egypt. We determined cancer mortality rates, and compared them with the Surveillance, Epidemiology, and End Results (SEER) mortality rates of the US. RESULTS: Bladder and liver cancers were the two most common causes of cancer mortality in Menofeia, Egypt. When adjusted for age the Egyptian rates were much higher than the US rates (9.5/100,000 and 8.4/100,000 for bladder and liver cancer, respectively, compared with 2.3/100,000 and 2.5/100,000 for the same cancers from SEER data). We also observed that age-specific rates for early-onset colorectal cancer under age 40 and premenopausal breast cancer were higher in Egypt than in the US. CONCLUSION: This study confirms our earlier observations about the higher proportion of early-onset colorectal cancer in Egypt, and opens the door for future studies to investigate familial clustering of cancer in Egypt.

Polymorphism of glutathione S-transferase loci GSTM1 and GSTT1 and susceptibility to colorectal cancer in Egypt.

Egypt has an unusually high proportion of early-onset colorectal cancer under age 40 years. Environmental exposures and low DNA repair capacity are among the risk factors. Because GSTM1 and GSTT1 gene deficiencies may act as risk modifiers for colorectal cancer risk, we investigated the relationship between genetic polymorphism in these genes and colorectal cancer risk in Egyptians. Sixty-six patients and 55 controls were included. Genotyping for GSTM1 and GSTT1 was conducted using PCR techniques and the results were related to epidemiologic and clinical information. No overall association was observed between GSTM1 or GSTT1 null genotypes and colorectal cancer risk. However, the data suggest a possible role for GSTM1 genotype in influencing tumor site. Furthermore, GSTM1 and GSTT1 genotypes, in conjunction with gender and place of residence, may play a role in modifying disease risk. Further studies on a larger population in Egypt are needed to generalize the results of this study.

A pyranocoumarin and two alkaloids (one with antispasmodic effect) from Citrus deliciosa.

One pyranocoumarin (xanthyletin, 1) and two acridone alkaloids (2',2'-dimethyl-(pyrano5',6':3:4)-1,5-dihydroxy, 6-methoxy, 10-methylacridone, 3, and citpressine-I, 4), were isolated from the roots of Citrus deliciosa Ten (Rutacea). Their structures were elucidated by spectroscopic methods. Reported 13C NMR assignments of alkaloid 3 have been corrected and those of alkaloid 4 are reported for the first time Alkaloid 3 was found to have antispasmodic effect on isolated ileum segments excised from male rabbits.

Familial aggregation of colorectal cancer in Egypt.

We have investigated the familial aggregation of colorectal cancer and hereditary nonpolyposis colorectal cancer (HNPCC) in Egypt because of the high incidence of colorectal cancer in Egyptian children and young adults and the prevalence of consanguinity there. In a pilot study, we conducted detailed interviews with 111 Egyptian colorectal cancer patients and 111 healthy Egyptian controls about their family histories of colorectal cancer, and other cancers, consanguinity, age at diagnosis, symptoms and recurrence. Eight patients (7.2%) had one or more first- or second-degree relatives under age 40 with colorectal cancer, suggestive of HNPCC by the Amsterdam criteria. One of these families had a typical history of HNPCC, with 4 relatives having colorectal cancer in 3 generations; 3 of these relatives were younger than age 45 at colon cancer diagnosis, and other relatives had extracolonic tumors. Another 14 patients (12.6%) had a first- or second-degree relative with a family history of other neoplasms such as endometrial, urinary and hepatobiliary cancers that could also be related to HNPCC. Four patients with early-onset colon cancer and a family history of other HNPCC-related cancers reported that their parents were first-degree cousins.

Reduced expression of mismatch repair genes in colorectal cancer patients in Egypt.

An Egyptian hospital-based pilot case-control study was conducted to investigate the relationship between the expression level of mismatch repair (MMR) genes and the risk of colorectal cancer. The relative expression of five known MMR genes, i.e., hMSH2, hMLH1, hPMS1, hPMS2, and GTBP/hMSH6, was measured by a multiplex reverse transcriptase (RT)-polymerase chain reaction (PCR) in peripheral blood lymphocytes from 31 colorectal cancer patients and 47 age- and-sex matched controls. The expression of hMSH2, GTBP/hMSH6, hPMS1 and hPMS2 tended to be lower in patients than controls, but only the difference in hPMS2 expression was statistically significant (p<0. 01). Although 50% of the cases had chemotherapy or radiotherapy within the last six months before the blood was drawn, their gene expression was not statistically different from those who had not undergone such therapies. After adjustment for age and sex, the odds ratios (OR) calculated from a logistical regression model, using the median levels of gene expression of controls as cut-off values, indicated that increased risk was associated with reduced expressions of both hPMS1 (OR = 3.97, 95% confidence interval (CI) = 1.04 to 7.65) and hPMS2 (OR = 2.86, 95% CI = 1.05 to 7.76). Although the results of this study were inconclusive because of the small sample size and use of prevalent cases, it is biologically plausible that patients with colorectal cancers may have a lower expression of MMR genes than healthy controls because malfunction of these genes has been shown in hereditary nonpolyposis colon cancer. The involvement of low hPMS2 expression in colon cancer risk seems to be unique in the Egyptian population. Further studies with newly diagnosed patients before they begin therapy will provide more convincing data about the role of MMR gene expression in the etiology of colorectal cancers in Egypt.

Knowledge of, attitudes toward, and barriers to cancer control and screening among primary care physicians in Egypt: the need for postgraduate medical education.

METHODS: The authors surveyed 177 primary care physicians in Menofeia, in the Nile Delta area of Egypt, to test their knowledge of, attitudes toward, and perceived barriers to cancer control and screening. RESULTS: The physicians viewed cigarette smoking and radiation exposure as the most important cancer risk factors, followed by occupation, family history, and sun exposure. The majority of the physicians saw diet as contributing little or nothing to cancer risk. Most of the physicians lacked knowledge about early cancer detection and screening. Junior practitioners, in particular, reported a lack of information about liver cancer and hepatitis viruses despite the prevalence of these viruses in the country. Large proportions of mid-career and senior primary care physicians who had no postgraduate education cited lack of knowledge and not being familiar with an approach to cancer prevention as reasons for not performing screening activities. CONCLUSION: The importance of smoking, diet, and early detection of common cancer types should receive more attention in the undergraduate medical curriculum of Egypt. Health and medical education authorities in Egypt should authorize more postgraduate education opportunities for senior primary care physicians, aimed at increasing their knowledge of prevention and improving their attitudes toward primary cancer prevention and screening.

Colorectal cancer in Egyptian patients under 40 years of age.

Although colorectal cancer is not a common cancer in Egypt, the age distribution of the disease shows that a high proportion occurs in children and adults under 40 years of age. We reviewed the records of 1,608 colorectal cancer patients treated in 4 cancer hospitals in Egypt during a period of 3 to 10 years. The hospitals in which about 85% of all colorectal cancer cases in Egypt were seen included Egypt's 2 major cancer centers, The National Cancer Institute (NCI) in Cairo and Tanta Cancer Center (TCC) in the mid-Nile Delta region, and 2 major university hospitals, Assiut University in South Egypt and Ain Shams University in Cairo. Our review showed that patients younger than 40 years represented 35.6% of all patients in the 4 cancer hospitals, and that these rates were similar among the hospitals and for the years reviewed. The male-to-female ratio increased from 1.0 to 1.7 for the age groups ranging from 0-9 and 30-39 years, and increased from 1.0 to 1.5 for the age groups ranging from 40-49 to over 60 years. More than half of all the patients had rectal tumors, and about 90% of the cancers were adenocarcinomas; 30.6% of patients younger than 40 years, compared with 13.8% of older patients, had mucin-producing tumors. This study confirmed the occurrence of a high colorectal cancer rate in young Egyptians, and it opens the door to future epidemiologic studies to identify causes and risk factors of this disease pattern in Egypt.