Early-Age-at-Onset Colorectal Cancer and Microsatellite Instability as Markers of Hereditary Nonpolyposis Colorectal Cancer

PURPOSE: Early-age-at-onset colorectal cancer and microsatellite instability are characteristic features of hereditary nonpolyposis colorectal cancer. Our aim was therefore to investigate whether these features might be useful markers in screening for hereditary nonpolyposis colorectal cancer and mismatch repair gene mutations. METHODS: From 1,132 consecutive patients who underwent surgery for colorectal cancer at our department between 1980 and 1999, we selected all patients 40 years of age or younger (study group, n = 59) and a subset of patients 40 years of age or older (control group, n = 60) who were matched for gender and pathologic TNM stage. Patients for whom a complete family cancer history or microsatellite status was unavailable were excluded from the study. Family cancer histories, retrieved from archival charts, were reassessed. Microsatellite status was investigated with the five microsatellites from the Bethesda recommended panel (BAT-26, BAT-25, D2S123, D5S346, and D17S250). On the basis of the number of altered microsatellites ( 2, 1, or 0), tumors were considered as having high or low instability or microsatellite stability, respectively. Mutation analysis for MLH1 and MSH2 genes was performed only in cases of high instability. DNA was investigated for mutations by single-strand conformational polymorphism and sequencing analysis. RESULTS: Data from 95 patients (study group: n = 37, 18 males, mean age 35 years; control group: n = 58, 29 males, mean age 62 years) were available for analysis. Four patients (study group, n = 3; control group, n = 1) fulfilled the Amsterdam II criteria for hereditary nonpolyposis colorectal cancer. Of the 37 study group tumors, 12 (32.4 percent) showed high-frequency microsatellite instability, and 25 had microsatellite stability, whereas among the 58 control group tumors, 4 (7 percent) showed high-frequency microsatellite instability, and 54 had microsatellite stability (P < 0.002). Mismatch repair gene mutation analysis was performed in 12 cases (study group, n = 7; control group, n = 5). We found four mutations (MSH2 119delG, MLH1 ex9 684insT, MSH2 Gln239Stop, and MLH1 del0.8 Kb) in the study group patients and none in the control group. Of four hereditary nonpolyposis colorectal cancer patients who underwent mismatch repair gene mutation analysis, one had a mutation. CONCLUSIONS: Early-age-at-onset colorectal cancer is significantly correlated with high-frequency microsatellite instability tumor status and is a useful criterion to identify hereditary nonpolyposis colorectal cancer patients. Moreover, when used in association with high-frequency microsatellite instability status, it is effective in selecting patients for mismatch repair gene mutation analysis.     

Comparison of Colorectal and Gastric Cancer: Survival and Prognostic Factors

Background/Aims:

Gastric and colorectal cancers are the most common gastrointestinal malignancies in Iran. We aim to compare the survival rates and prognostic factors between these two cancers.

Methods:

We studied 1873 patients with either gastric or colorectal cancer who were registered in one referral cancer registry center in Tehran, Iran. All patients were followed from their time of diagnosis until December 2006 (as failure time). Survival curves were calculated according to the Kaplan-Meier Method and compared by the Log-rank test. Multivariate analysis of prognostic factors was carried out using the Cox proportional hazard model.

Results:

Of 1873 patients, there were 746 with gastric cancer and 1138 with colorectal cancer. According to the Kaplan-Meier method 1, 3, 5, and 7-year survival rates were 71.2, 37.8, 25.3, and 19.5%, respectively, in gastric cancer patients and 91.1, 73.1, 61, and 54.9%, respectively, in patients with colorectal cancer. Also, univariate analysis showed that age at diagnosis, sex, grade of tumor, and distant metastasis were of prognostic significance in both cancers (P < 0.0001). However, in multivariate analysis, only distant metastasis in colorectal cancer and age at diagnosis, grade of tumor, and distant metastasis in colorectal cancer were identified as independent prognostic factors influencing survival.

Conclusions:

According to our findings, survival is significantly related to histological differentiation of tumor and distant metastasis in colorectal cancer patients and only to distant metastasis in gastric cancer patients.     

Incidence,diagnostic, treatment and outcome of patients diagnosed with cancer of the pancreas during 1986–2009: a population-based study

Objective: Limited data exist on the changes in the epidemiology of pancreatic cancer and outcomes over the last decades in population-based cohorts. We aimed to compare the incidence of pancreatic cancer, diagnostic, treatment and survival among patients diagnosed over the period 1986–2009.

Materials and methods: A retrospective, nationwide, population-based study. All patients diagnosed with pancreatic cancer in Iceland in two periods, 1986–1997 (P1) and 1998–2009 (P2) were identified through the Icelandic Cancer Registry and relevant clinical information obtained from medical records.

Results: A total of 645 patients were identified, 296 in P1 and 349 in P2 (NS). The incidence during P1 was 6.8 per 100,000 inhabitants and 6.2 during P2 (NS). Among biopsy-proven cancers, adenocarcinoma was diagnosed in 89% of the cases in P1 and in P2 in 93% of the cases. Overall 38 (14%) in P1 underwent resection and 22 (7%) in P2 (p?p?=?.015, log-rank test) and one year (p?=?.0206) after diagnosis. A total of 4/296 (1.4%) in P1 survived more than 5 years and 3/349 (0.9%) in P2 (NS).

Conclusions: The incidence among patients with pancreatic cancer in Iceland did not show major changes during the last 20 years. Diagnostic approach has changed considerably demonstrating more patients that are not ‘resectable’. Survival rate at 6 months and one year has improved over the last two decades whereas the 5-year prognosis has not improved.     

Female breast cancer incidence and mortality in 2011, China

Background

Breast cancer is the most common cancer diagnosis in women. During the past 30 years, mortality of breast cancer in Chinese women showing a gradual upward trend, it has become the crucial death reasons of female.

Methods

In 2014, there were 234 population-based cancer registries submitting their data of 2011 to the National Central Cancer Registry (NCCR) of China and 177 cancer registries’ data were selected after quality evaluation. The selected cancer registries were classified as urban areas and rural areas, in each level. The crude incidence and mortality rates of female breast cancer were calculated by age-groups. Age-standardized rates were described by China and World standard population. And the national population data of China was used to combine with the cancer registries’ data to estimate the female breast cancer burden in 2011 in China.

Results

The estimated number of female breast cancer cases was 248,620. The crude incidence rate, age-standardized rate by China and World population were 37.86 per 100,000, 28.51 per 100,000 and 26.65 per 100,000, respectively. The estimated number of female breast cancer death in 2011 of China was about 60,473. The crude, age-standardized mortalities by China population and World population were 9.21 per 100,000, 6.57 per 100,000 and 6.38 per 100,000, respectively. The incidence and mortality rates were both higher in urban areas than rural areas. Trend of age-specific incidence rates in urban and rural was similar, reaching peak at 55-59 years old. The trend of age-specific mortality rates was very similar before 60 between urban and rural areas, but after that, the urban areas curve was rapidly mounting as the age growing and much higher than rural.

Conclusions

Breast cancer is still a major health burden for Chinese women especially in urban areas. Prevention strategies such as weight control, high-quality screening, diagnosis and treatment may help control the disease.     

The Prognostic Significance of E-Cadherin and Liver Intestine-Cadherin Expression in Colorectal Cancer

PURPOSE: The significance of liver intestine-cadherin as a potential marker has been growing in the field of oncology, because of its unique features compared with classic cadherins. We investigated the coexpression patterns of E-cadherin and liver intestine-cadherin in colorectal cancer, and determined whether differences in expression patterns were associated with clinicopathologic parameters and also which relationship between these two adhesion molecules existed in colorectal cancer. METHODS: Expression pattern of E-cadherin and liver intestine-cadherin was investigated immunohistochemically in 207 colorectal cancers along with clinicopathologic parameters. RESULTS: Reduced expression of liver intestine-cadherin was detected in 51 percent (n = 105) of tumors. Such expression was found to be associated with tumoral dedifferentiation (P = 0.015) and in a multivariate analysis was associated with a significant worse overall survival after adjustment for tumor stage, differentiation, and E-cadherin status (hazard ratio, 1.951; 95 percent confidence interval, 1.06-3.592; P = 0.032). Fifteen percent (n = 32) of tumors showed reduced expression of E-cadherin and had relationship with tumoral dedifferentiation (P < 0.001), lymph node metastasis (P = 0.004), and advanced stage (P = 0.029). Reduced expression of E-cadherin was associated with short overall survival (P = 0.028); however, in a multivariate analysis, it was not statistically significant. CONCLUSIONS: Reduced expression of liver intestine-cadherin had a significant correlation with tumoral dedifferentiation and short overall survival in this series. In addition, early and frequent loss of liver intestine-cadherin expression might be a more sensitive indicator than E-cadherin to predict more aggressive tumoral behavior.     

Prognostic factors and patients’ profile in treated stage I and II lung adenocarcinoma: a Hospital’s Cancer Registry-based analysis

BackgroundIt is known that survival from lung cancer can differ between countries and even between different regions of the same country. The variability between hospitals, the age and social profile, and the time when this patient was treated, can influence survival, and these factors are intrinsic to each region. Knowing the profile of patients, hospitals, and other factors associated with the treatment of stage I and II lung cancer in a given region is important to understand outcomes and propose improvements that can be replicated in any region of the world that presents the same profile of patients and care structure. This study evaluates survival and possible predictors in all patients with stage I and II lung cancer adenocarcinoma through the Hospital’s Cancer Registry (HCR), responsible for the State of Sao Paulo’s cancer registry, a geographical area with 40 million inhabitants.MethodsBased on the HCR, an observational study was conducted, including 1,278 patients diagnosed with lung adenocarcinoma at clinical stages (CS) I and II. Sex, age at diagnosis, education, neighbourhood, CS at diagnosis, the time between diagnosis and treatment, 5-year periods in which patients were treated, treatment modality and hospitals where patients were treated were analysed. Cox univariate and multiple regression analyses were used to estimate the hazard ratio (HR).ResultsA total of 1,278 lung cancer patients with clinical lung cancer adenocarcinoma stages I and II were included. About 40.06% of patients did not receive surgery, and only 55.8% started the treatment within 2 months. The majority of the patients were treated in high complexity hospitals, 69%. Five-year overall survival (OS) was 45.6% in CS I and 27.5% in CS II. Patients treated in high complexity centres have lower mortality rates than those treated in Partial Hospital Complexity Centers in Oncology (PHCCO) (adjHR 1.18; 95% CI: 1.00–1.40; P=0.047). Patients diagnosed between 2010–2014 had a protective factor against the risk of death concerning patients diagnosed between 2000–2004.ConclusionsThe 5-year OS has significantly improved as long as the 5-year group analysed. Also, the 5-year OS of the patients treated in high complexity hospitals is higher than those treated in PHCCO.     

Primary therapy and survival among patients with nodular lymphocyte-predominant Hodgkin lymphoma: a population-based analysis in the Netherlands, 1993–2016

In this nationwide, population-based study, we assessed trends in primary treatment and survival among 687 patients with nodular lymphocyte-predominant Hodgkin lymphoma (75% males; median age, 40 years; and 74% stage-I/II disease) diagnosed in the Netherlands between 1993–2016. There were no noteworthy changes in the application of primary therapy over time among adult patients across the different disease stages and age groups. Survival among various subgroups of adult patients was largely comparable to the expected survival of the general population. A particularly encouraging finding was that young adult patients experienced virtually no excess mortality, as compared to the general population.     

Epidemiology of pancreatic cancer in Northeastern Italy: incidence, resectability rate, hospital stay, costs and survival (1990–1992)

BACKGROUND: The incidence of pancreatic cancer and relative hospital stay and costs are not well known. AIMS: To define the incidence, hospital stay and cost of pancreatic cancer in a well-defined area of Italy. PATIENTS AND METHODS: Each new case of pancreatic cancer diagnosed between 1990 and 1992 among 669,703 inhabitants in the Veneto Region of Northern Italy was recorded and followed until death or for 5 years after diagnosis. Four types of hospital stay were defined. Type 1: undiagnosed pancreatic cancer; type 2: first diagnosis of pancreatic cancer, treatment excluded; type 3: main treatment; and type 4: follow-up and disease-related complications. Data were analysed for hospital stay-related procedures, costs and survival. RESULTS: Pancreatic cancer was diagnosed in 253 patients (12.6/100,000 per year), 43 patients (17.7%) underwent surgical resection, and 93 (36.8%) palliative surgery. The mean duration of type 3 hospital stay was similar for resection, palliative and exploratory surgery. The estimated hospital cost was significantly higher for surgical resection, almost the same for palliative and exploratory surgery, and only slightly lower for medical treatment. Each patient spent a mean of 57.7 days in the hospital. The hospital mortality rate was 4.6% for surgical resection, 22.1% for palliative surgery, and 18.7% for exploratory laparotomy. Overall, the 1-, 2-, 3- and 5-year survival rates were 20.9%, 5.1%, 2.9% and 1.2%, respectively. CONCLUSIONS: Pancreatic cancer is an expensive, almost incurable disease. Integrated treatments in specialized Centres should reduce the mortality rate and costs.     

Differential Prognostic Significance of Morphologic Invasive Markers in Colorectal Cancer: Tumor Budding and Cytoplasmic Podia

Purpose In colorectal cancer, the presence of cytoplasmic podia around tumor budding foci may be a morphologic marker for an activated budding phenotype that is associated with cell motility. In this study, we have investigated the prognostic significance of cytoplasmic podia. Methods A total of 136 pT3 colorectal cancers were classified according to extent of budding and cytoplasmic podia as identified by immunostaining for cytokeratin. The prognostic significance of budding and cytoplasmic podia was then assessed. Results The overall survival curves between the groups with high-grade and low-grade cytoplasmic podia were different (5-year survival rates were 60.5 and 83.8 percent respectively, P = 0.0003). Similar results were shown for tumor budding (59.8 and 87.7 percent, P < 0.0001). Multivariate analysis showed that the grades of cytoplasmic podia (hazards ratio, 2.4; P = 0.012) and budding (hazards ratio, 2.3; P = 0.024) were independent prognostic factors. Additionally, among colorectal cancers with high-grade budding, the grade of cytoplasmic podia was selected as an independent prognostic factor (hazards ratio, 2.4; P = 0.042). Conclusions Cytoplasmic podia and budding are related but independent pathologic predictive markers in patients with resected pT3 colorectal cancer.     

Female breast cancer statistics of 2010 in China: estimates based on data from 145 population-based cancer registries

Background

The aim of the study is to provide incidence and mortality data of female breast cancer at national level of China in 2010.

Methods

A total of 145 population-based cancer registries submitted qualified cancer incidence and mortality data to National Cancer Registration Center of China. Based on the qualified cancer registries’ data, we estimated the overall breast cancer incidence and mortality data of China in 2010 and reported breast cancer statistics by age and geographical area.

Results

The estimated number of female breast cancer cases was about 208 thousand. The crude incidence rate, age-standardized rate by China and World population were 32.43 per 100,000, 25.89 per 100,000 and 24.20 per 100,000, respectively. The incidence rates were higher in urban area than in rural area. And the incidence rates in Eastern area and Middle area were similar and higher that those in Western areas. The estimated number of female breast cancer death in 2010 of China was about 55.5 thousand. The crude, age-standardized mortalities by China population and World population were 8.65 per 100,000, 6.56 per 100,000 and 6.36 per 100,000, respectively. The mortality rates by geographical area had similar pattern to the incidence rates.

Conclusions

Breast cancer is still a major health burden for Chinese women especially in urban area. Prevention strategies such as weight control, high-quality screening and diagnosis may help control the disease.     

Prediction of Postoperative Mortality in Elderly Patients With Colorectal Cancer

Purpose This study was designed to develop a model for predicting postoperative mortality in elderly patients undergoing surgery for colorectal cancer. Methods This multicenter study was conducted by using routinely collected clinical data, assessing patients older than aged 80 years, with 30-day operative mortality as the primary end point. Data were collected from The Association of Coloproctology of Great Britain and Ireland database, encompassing 8,077 newly diagnosed colorectal cancer patients undergoing resectional surgery in 79 hospitals between April 2000 to March 2002, The Association of Coloproctology Malignant Bowel Obstruction Study, encompassing 1,046 patients with malignant bowel obstruction in 148 hospitals, between April 1998 to March 1999, and The Wales-Trent audit, encompassing 3,522 newly diagnosed colorectal cancer patients, between July 1992 to June 1993. A multilevel logistic regression model was developed to adjust for case-mix and to accommodate the variability of outcomes between the three study populations. The model was internally validated using a Bayesian resampling technique and tested using measures of discrimination, calibration, and subgroup analysis. Results A total of 2,533 patients satisfied the inclusion criteria, with a 30-day mortality of 15.6 percent. Multivariate analysis identified the following independent risk factors: age (odds ratio for 85–90, 90–95, >95 vs. 80–85 = 1.1, 1.8, 2.9), American Society of Anesthesiology grade (odds ratio for Grade III, IV vs. I–II = 2.7, 6.1), operative urgency (odds ratio for emergency vs. elective = 1.9), no cancer excision vs. resection (odds ratio = 1.2), and metastatic disease (odds ratio for metastases vs. no metastases = 1.9). The model offered adequate discrimination (area under receiver operator curve = 0.732) and excellent agreement between observed and predicted outcomes during eight colorectal procedures (P = 0.885). Conclusions The elderly colorectal cancer model can accurately estimate 30-day mortality in patients older than aged 80 years undergoing surgery for colorectal cancer. Because the mortality can be considerable, this may have important implications when determining management for this group of patients. Poster presentation at the meeting of The American Society of Colon and Rectal Surgeons, Dallas, Texas, May 8 to 13, 2004, and the meeting of The Association of Coloproctology of Great Britain and Ireland, Birmingham, United Kingdom, June 28 to July 1, 2004.     

Epidemiology of systemic sclerosis in northwest Greece 1981 to 2002

OBJECTIVES: To investigate the incidence and prevalence, as well as the mortality and survival rates, of systemic sclerosis (SSc) in a defined area of northwest Greece with a population of about 500,000 inhabitants. MATERIALS AND METHODS: Cases have been recorded from the following sources: (1) inpatients and outpatients referred to the Rheumatology Clinics of the Ioannina University Hospital and the Ioannina General Hospital; (2) patients referred to the private rheumatologists practicing in the study area. All patients recorded between 1/1/1981 and 31/12/2002, resident in the study area, were included in the study. Diagnosis was based on the American College of Rheumatology classification criteria for SSc. Incidence and prevalence rates were calculated as number of cases per 10(5) inhabitants. Population data were based on the National Census of 1981, 1991, and 2001. RESULTS: The age-adjusted prevalence of SSc was 15.40 cases/10(5) inhabitants on 31/12/2002. A total of 109 new cases were diagnosed during the study period, giving a mean annual age-adjusted incidence rate of 1.10 cases/10 5 inhabitants. There were 98 women and 11 men, giving a ratio of 8.9/1. Limited SSc was diagnosed in 75% and diffuse in 25% of the patients. Esophageal involvement was found in 59%, lung involvement in 56%, and renal disease in 5%. Thirty-six deaths were recorded during the study period in this incidence cohort. The 5-year survival rate was 83% and the 10-year survival rate was 70%. CONCLUSIONS: The incidence and prevalence of SSc in northwest Greece were found to be lower than those of the USA and Australia, and higher than those of northern European countries and Japan. The survival rates were similar to those reported by other studies.     

Exploring contrary trends in bladder cancer incidence,mortality and survival: implications for research and cancer control

Aim: To investigate trends in bladder cancer incidence, mortality and survival, and cancer–control implications. Methods: South Australian Registry data were used to calculate age‐standardized incidence and mortality rates from 1980 to 2004. Sociodemographic predictors of invasive as opposed to in situ disease were examined. Determinants of disease‐specific survival were investigated using Kaplan–Meier estimates and proportional hazards regression. Results: Incidence rates for invasive cancers decreased by 21% between 1980–84 and 2000–04, similarly affecting men and women. Meanwhile increases occurred for combined in situ and invasive disease. While mortality rates decreased by approximately a third in men and women less than 70 years of age after the early 1990s, no changes were evident for older residents. The proportion of cancers found at an in situ stage was higher in younger ages and more recent diagnostic periods. Five‐year survivals of invasive cases decreased from 64% for 1980–84 diagnoses to 58% for 1995–2004. Multivariable analysis showed that diagnostic period was not predictive of survival after age adjustment (P= 0.719), with lower survival relating to older age, transitional compared with papillary transitional cancers, female sex, indigenous status and a country as opposed to metropolitan residence. Conclusions: Reductions in invasive disease incidence may be due to increased detection at an in situ stage. The decline in survival from invasive disease in more recent periods is explained by increased age at diagnosis. Poorer outcomes of invasive cases remain for women after adjusting for age, histology, indigenous status and residential location.     

Prognostic factors for long-term survival in patients with locally invasive pancreatic cancer

Background/Purpose

We aimed to investigate predictors of survival in patients with resectable locally invasive pancreatic cancer.

Methods

The patient cohort consisted of 55 patients with locally invasive pancreatic cancer (International Union Against Cancer [UICC] stage III in 36 patients and stage IV in 19) who had undergone resection. The patients were informed about the advantages and the adverse effects of postoperative chemotherapy, and prospectively selected either observation alone or postoperative chemotherapy. The postoperative chemotherapy regimen options were: (1) intraarterial chemotherapy alone, (2) systemic chemotherapy alone, or (3) intraarterial chemotherapy combined with systemic chemotherapy.

Results

Overall 1-year and 2-year survival rates after resection were 40.5% and 13.5%, respectively. Median survival time was 10.9 months. Twenty-nine patients (52.7%) received postoperative chemotherapy. On univariate analysis, only postoperative chemotherapy was associated with long-term survival (P < 0.01). In the patients with postoperative chemotherapy, the 1-year survival rate and MST were 61.7% and 16.3 months, compared with 20.1% and 7.9 months in the patients without postoperative chemotherapy. Multivariate analysis also showed that only postoperative chemotherapy was identified as an independent survival factor.

Conclusions

It was suggested that postoperative chemotherapy was essential for the improvement of survival in patients with locally invasive pancreatic cancer.

     

Prognostic Significance of Hereditary Predisposition on the Outcome of Colorectal Cancer as Expressed by Increased in Vitro Tetraploidy

Seventy colorectal cancer patients operated on in the period 1981–1984 were consecutively investigated for in vitro tetraploidy in dermal fibroblasts, as an increased number of tetraploids is considered a marker of genetic predisposition for colorectal cancer. The difference in disease-free survival rates of increased (IVT⁺) and normal (IVT^?) in vitro tetraploidy was not statistically significant (0.1 < p < 0.2), but the decrease in the disease-free survival rate of IVT⁺ was 1.6 times that of IVT^?. To exclude the influence of other prognostic factors, a Cox multivariate regression analysis was used, with Dukes C carcinoma and poor differentiation as co-variables for IVT⁺. In this analysis IVT⁺ did not show any independent prognostic significance. A genetic predisposition for colorectal cancer, as expressed by the presence of IVT⁺ in skin fibroblasts, does not seem to influence the survival of patients with colorectal cancer.     

Circulating p53 Antibody in Patients with Colorectal Cancer

The presence of serum anti-p53 antibody has been reported to be associated with survival of patients with breast cancer, ovarian cancer, and hepatocellular carcinoma. To clarify prognostic significance of p53 antibody in colorectal cancer, serum p53 antibody was measured in patients with colorectal cancer. The 89 patients included 71 with colorectal cancer and 18 with colon polyp. An enzyme-linked immunosorbent assay was used to detect p53 antibodies in serum. Clinicopathological parameters such as age, sex, degree of differentiation of cancer, location of tumor, liver metastasis, stage classification, Dukes classification, CEA, CA19-9, and immunostaining of p53 and anti-p53 antibody were evaluated as prognostic factors of colorectal cancer. p53 antibody was positive in 18 of 71 (25%) with colorectal cancer, whereas it was positive in only 1 of 18 (6%) with colon polyp. The patients with p53 antibody had higher CEA and CA19-9 levels, higher positive rates of p53 protein expression in cancer cells, and higher liver metastasis rates. The p53 antibody positivity at stage classification I–IIIb/Dukes classification A–C was significantly lower than that at stage classification IV/Dukes classification D. Overall survival in colorectal cancer patients with p53 antibody was significantly shorter than in those without p53 antibody. A Cox regression analysis showed that liver metastasis, stage classification, Dukes classification, CA19-9, and p53 antibody were significant prognostic factors in colorectal cancer. Serum anti-p53 antibody could serve as one of the prognostic factors in patients with colorectal cancer.