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Adjuvant tamoxifen therapy for early stage breast cancer and second primary malignancies. Stockholm Breast Cancer Study Group.

BACKGROUND: Tamoxifen is being increasingly used for the treatment of breast cancer and is undergoing study for the primary prevention of breast cancer. However, concerns have been raised that the drug may increase the incidence of new primary malignancies, such as endometrial, liver, and colorectal cancers. PURPOSE: Our goal was to assess the carcinogenic risks associated with long-term use of tamoxifen in women with early stage breast cancer. METHODS: The incidence of new primary cancers among 2729 women participants of the Stockholm Trial was determined at a median follow-up of 9 years. In this trial, after primary surgery, postmenopausal patients aged less than 71 years with unilateral invasive breast cancer were randomly allocated to receive either 2 years of adjuvant tamoxifen (40 mg daily) or no adjuvant endocrine therapy. Information on second cancers was obtained by retrospective linkage to the Swedish Cancer Registry. To increase statistical power, a joint analysis of the incidence of endometrial and gastrointestinal cancers was performed in the following three major studies in Scandinavia evaluating adjuvant tamoxifen therapy: the Stockholm Trial, the Danish Breast Cancer Group Trial, and the South-Swedish Trial. These studies included a total of 4914 patients with a median follow-up of 8-9 years. All P values were calculated from two-tailed tests of statistical significance. RESULTS: In the Stockholm Trial, there was a statistically significant (P = .008) reduction in the incidence of second primary cancers in the contralateral breast among the tamoxifen-treated patients. However, there was a nearly sixfold increase in endometrial cancers (P < .001) and a threefold increase in gastrointestinal cancers in the tamoxifen-treated patients. The results of the joint studies showed a statistically significant increase in endometrial cancers among the tamoxifen-treated patients (relative risk [RR] = 4.1; 95% confidence interval [CI] = 1.9-8.9). There was also an excess of gastrointestinal cancers associated with tamoxifen. Most of this excess involved colorectal cancers (RR = 1.9; 95% CI = 1.1-3.3) and stomach cancer (RR = 3.2; 95% CI = 0.9-11.7). There was no substantial increase in any other type of gastrointestinal cancer (e.g., liver cancer) among the tamoxifen-treated patients. CONCLUSION: The endometrium and gastrointestinal organs may be target sites for tamoxifen-induced carcinogenesis in humans. IMPLICATIONS: The increased incidence of colorectal and stomach cancers reported here should be regarded as tentative until supported by long-term data from a larger number of tamoxifen trials. Also, appropriate surveillance of cancer incidence is warranted for the protection of participants enrolled in current tamoxifen chemoprevention trials.

Aged↗

Second lung cancers in patients after treatment for an initial lung cancer.

BACKGROUND: Prospectively and retrospectively identified patient cohorts that were successfully treated for primary lung cancer have been followed to document the rate of development of and the effectiveness of treatment of second lung cancers. This review was performed to assess rates of second lung cancer development, factors associated with the development of these cancers, and the success of their treatment. METHODS: The MEDLINE database was searched to identify articles published in English concerning lung cancers, second primary cancers, treatment of these cancers, and patient survival. RESULTS: The risk of developing a second lung cancer in patients who survived resection of a non-small-cell lung cancer is approximately 1%-2% per patient per year. Approximately one half of the patients who develop second non-small-cell lung cancers can have these tumors resected. The median survival from diagnosis of a second lung cancer in these patients is between 1 and 2 years, with a 5-year survival of approximately 20% (range, 4%-32%). The average risk of developing a second lung cancer in patients who survived small-cell lung cancer is approximately 6% per patient per year. For patients who survived small-cell cancer, the risk increases from approximately 2% to greater than 10% per patient per year 10 years after initial treatment. Only 7% (range, 6%-12%) of patients treated for small-cell lung cancer survive 2 years or more. Survivors who continue to smoke cigarettes have an increased risk of developing a second lung cancer. CONCLUSIONS: In patients surviving an initial lung cancer, the cumulative risk for the development of a second primary lung cancer makes this cancer a common cause of death. The high risk of developing a second lung cancer makes patients with these cancers an important population for study of surveillance strategies and chemoprevention agents.

Carcinoma, Non-Small-Cell Lung↗

Clinicopathologic characteristics and prognoses of gastric cancer in patients with a positive familial history of cancer.

BACKGROUND: There is a significant association between a positive family history of cancer and gastric cancer risk; however, the clinicopathologic characteristics and prognoses of gastric cancer patients with a positive family history of cancer are not clear. GOALS: To define the clinicopathologic characteristics and prognoses of gastric cancer patients with a positive family history of cancer. STUDY: We reviewed 548 patients with pathologically confirmed primary gastric cancer who had undergone a gastrectomy between 1990 and 1996. The average age was 59.7 years, and the male-to-female ratio was 1.7. The familial cancer histories of these patients were reviewed, and the various clinicopathologic characteristics of those patients with a positive family history of cancer were compared with those with a negative history. RESULTS: Among this cohort, 74 (13.5%) patients had a positive family history of cancer in their primary or secondary relatives. The most common cancer was gastric cancer in 29 patients, followed by colorectal cancer in 10 and lung cancer in 7. Patients with a positive family history of cancer were associated with bigger tumors, and more patients received a total gastrectomy than did patients with a negative family history. Immunopathologic study disclosed a higher rate of p53 overexpression but not of neu or c-met in patients with a positive family history of cancer. There were no differences in the mean age, gender, site, depth of invasion, or TNM stage. The survival curve of patients with a positive family history of malignancy was similar to that of patients without a family cancer history. CONCLUSION: Patients with gastric cancer with a positive family history of cancer appeared to have bigger tumors with a higher rate of p53 overexpression, and more patients required a total gastrectomy compared with those with a negative family history. This study suggests a genetic component in the aggressiveness of gastric cancer and indicates that higher caution should be exercised with people who have a positive family history of cancer.

Aged↗

Clinical characteristics of bladder cancer in patients previously treated with radiation for prostate cancer.

OBJECTIVE: To determine if bladder cancer diagnosed after prostatic radiation therapy (RT) differs in behaviour from bladder cancer diagnosed after prostate cancer not treated with RT, as such bladder cancer is thought to be more aggressive than de novo bladder cancer, and epidemiological studies show a higher rate of bladder cancer in patients after irradiation. PATIENTS AND METHODS: We reviewed our records to identify patients who had a diagnosis of bladder cancer with a previous diagnosis of prostate cancer. Patient age, date of diagnosis of prostate cancer, date of diagnosis of bladder cancer, symptoms, clinical stage, initial pathology, definitive therapy, definitive pathological stage, and disease status were recorded. RESULTS: In all, 100 patients were identified who had a diagnosis of bladder cancer after a diagnosis of prostate cancer between January 1992 and August 2003; 58 had had RT for prostate cancer. The mean time between a diagnosis of bladder cancer and prostate cancer was 62 months in the RT group and 34 months in the unirradiated group (P = 0.002) At diagnosis of bladder cancer, 56 (97%) of the patients who received RT had high-grade urothelial carcinoma, vs 27 (64%) of those not irradiated (P < 0.001). Thirty (52%) of the patients with RT had muscle-invasive bladder cancer, vs 17 (40%) of those not irradiated (P = 0.3). The survival rate was similar for both groups. CONCLUSIONS: Bladder cancer is diagnosed later, and is of higher grade, in patients who are irradiated for prostate cancer than in those treated with other methods. Patients with prostate cancer who are treated with RT should be monitored closely for the presence of bladder cancer.

Aged↗

Cancer worry in women with hereditary risk factors for breast cancer.

PURPOSE/OBJECTIVES: To investigate symptom-based cancer worry in women who are at hereditary risk for breast cancer, specifically levels of worry, correlations of cancer worry, perceived cancer risk, and clinical signs or symptoms of breast cancer, as well as predictors of cancer worry. DESIGN: Cross-sectional, correlational. SETTING: Primarily the United States. SAMPLE: 200 women, aged 18-80, with no personal history of cancer, who met at least one established criterion of hereditary breast cancer risk were recruited primarily from a mammography facility and cancer prevention clinics or via network sampling. METHODS: Completion of the following self-report instruments: Thoughts About Cancer Scale and measures of clinical symptoms, perceived risk, and sample characteristics. Data analysis consisted of descriptive statistics, Pearson correlations, and binary logistic regression. MAIN RESEARCH VARIABLES: Cancer worry, total clinical signs of cancer, perceived cancer risk, age, and family history. FINDINGS: Participants sometimes worried about breast cancer but had more general breast cancer worry than worry based on perceived neutral or breast cancer-specific symptoms. Total clinical signs of breast cancer correlated significantly with cancer worry. Women aged 41-50 and those with more clinical signs of breast cancer were 3.76 and 1.49 times more likely to have high worry, respectively. CONCLUSIONS: Moderate worry in high-risk women is not unusual. Total symptoms and younger age predict higher breast cancer worry, whereas perceived risk and family history do not. IMPLICATIONS FOR NURSING: Counseling of young, high-risk women should include assessments of worry and clinical signs of breast cancer.

Adolescent↗

Endometrial cancer in the family-cancer database.

Endometrial cancer was studied in the Swedish Family-Cancer Database, updated in 1999 to cover individuals born after 1934 with their biological parents, totaling 9.6 million persons. Cancer data were obtained from the Swedish Cancer Registry from 1958 to 1996 and included over 20,000 cases of endometrial cancer. Seventy-six families were identified in which both the mother and the daughter had endometrial cancer, giving a familial standardized incidence ratio (SIR) of 3.19 for daughters and 2.78 for mothers. The risk depended inversely on the age at diagnosis, and the risk was almost 10 in daughters who were diagnosed before age 50 when their mothers were also diagnosed before that age. The discordant cancer site that associated with endometrial cancer between the two generations was colon, with a SIR of 1.44-1.68. However, when the maternal endometrial cancer was diagnosed before age 50, increased SIRs were observed in daughters or sons for rectal, pancreatic, nervous system, breast, and ovarian cancers. Second cancers were followed in females diagnosed with endometrial cancer, and the highest overall risks were observed for ovarian and connective tissue cancers; colorectal cancers were also clearly in excess. Among the other family members of the 76 families in which both mother and daughter were affected with endometrial cancer, there were 11 cases of colorectal cancer. When a sister was affected in such families, the SIR of endometrial cancer was 31.40, and the median diagnostic age was several years lower than in endometrial cancer families in which no colorectal cancers were found. Many of these families may have hereditary nonpolyposis colorectal carcinoma syndrome. However, the risk of endometrial cancer was increased even in families presenting no colorectal cancers.

Adolescent↗

Cancer registration in Germany: current status, perspectives and trends in cancer incidence 1973-93.

BACKGROUND: A federal law effective in 1995 makes it mandatory for all German States to build up population-based cancer registries. Although the law provides a model of cancer registration, each State may modify this by State-specific regulations, as long as they ensure data exchange between the registries and between registries and scientific institutions. The 'Network of German Population-Based Cancer Registries' constitutes the basis for cooperation among the German cancer registries. In order to improve the cooperation between physicians and epidemiologists, and to demonstrate the benefits of cancer registration, the network published a booklet containing facts on time-trends in cancer incidence during the last two decades. METHODS: Information on cancer incidence and mortality was derived from the population-based cancer registries of Saarland, the former German Democratic Republic (until 1989), the City of Hamburg and the region of Münster. Altogether these registries cover a population of about 23 million. Sixteen types of cancer were selected for the analyses. RESULTS: Major increases in cancer incidence were observed for female lung cancer, testicular cancer, cancer of the oral cavity, malignant melanoma of the skin and non-Hodgkin's lymphoma. Incidence rates also increased for cancer of the female breast, prostate cancer and colorectal cancer. A decrease was observed for stomach and cervical cancer. DISCUSSION: In 1998, only a small fraction of all German adults were monitored by a population-based cancer registry, making it impossible to work out accurate incidence rates for the whole of Germany. Several new cancer registries have been built up recently. Data summaries of existing German population-based cancer registries assist in enhancing the completeness of new cancer registries.

Female↗

Comparisons of interval breast cancers with other breast cancers detected through mass screening and in outpatient clinics in Japan.

In a nation-wide collaborative study on mass screening for breast cancer, we collected 152 cases of interval breast cancer diagnosed at 35 hospitals or clinics distributed throughout Japan. The definition of interval breast cancer used in the present study is "breast cancer cases which were diagnosed as having 'no malignant findings' in a previous screening for breast cancer but subsequently diagnosed as 'breast cancer' at a hospital or medical clinic within two years of the previous screening." The clinical stages and prognoses of these interval cancer were analyzed and compared with those of other breast cancers detected through mass screening and in outpatient clinics. In the clinical staging of interval breast cancer, Tis (non infiltrating cancer) accounted for only 2.1%, compared to 8.0% in cases detected through mass screening. At stage I 43.4% were interval breast cancers compared to 32.9% breast cancers detected through mass screening and 25.4% diagnosed in outpatient clinics. The stage differences between interval breast cancers and breast cancers detected through mass screening were not statistically significant. Five-year survival rates were 85.6% for interval breast cancers, 91.7% for breast cancers detected through mass screening and 84.7% for breast cancers diagnosed in outpatient clinics. Ten-year survival rates were 75.9, 80.5 and 78.1%, respectively, suggesting the interval breast cancer cases to show a similar prognosis to that of breast cancer cases diagnosed in outpatient clinics. The differences in five- and 10-year survival rates among the three groups were not statistically significant. From the present study we were not able to confirm the general belief of interval cancer being more aggressive in nature and showing a poorer prognosis than cancer detected through periodic screening. The reasons for this are discussed.

Adult↗

Cancer registration in Connecticut and the study of multiple primary cancers, 1935-82.

The Connecticut Tumor Registry (CTR) was established in 1941 and is the oldest population-based cancer registry in the world. Since 1935, all malignant tumors have been registered, and cancer patients are followed annually for vital status. Reporting by hospitals of all cancers diagnosed in Connecticut residents became mandatory in 1971. The reporting physician or hospital makes the initial determination as to whether a tumor is an independent primary cancer, recurrent tumor, or metastatic lesion. In addition, the Registry maintains stringent quality control procedures to avoid duplication of cancer reports. The Registry reviews reports of new cancers developing in patients with a previous primary cancer to rule out the possibility of misdiagnosed metastases. Microscopic confirmation of the diagnosis has improved from 49% in 1935-39 to 94% in 1980-82. Cancers reported only from death certificates currently account for only 1% of all registrations. Between 1935 and 1979, cancer rates in Connecticut almost doubled among males and increased by more than one-third among females; notable increases were seen for cancers of the lung and prostate in males and cancers of the lung and breast in females. In recent years, rates for malignant melanoma of the skin have increased dramatically among both sexes. Stomach cancer has decreased over time in both sexes, as has cervical cancer in females. Although the CTR has used several revisions of the International Classification of Diseases to code the primary site of cancers, rules for the coding of multiple primary cancers have remained essentially the same. Among 253,536 individuals diagnosed between 1935 and 1982 with an invasive cancer, 16,727 (6.6%) nonsimultaneous second cancers were evaluated and are discussed in subsequent chapters of this monograph. Simultaneous cancers were diagnosed in 4,107 individuals and accounted for approximately 20% of all multiple cancers reported in Connecticut. The most frequent simultaneous tumors were cancers of the colon, rectum, prostate, lung, breast, and bladder. Some simultaneous cancers (chronic lymphocytic leukemia, testis, prostate, rectum, uterine corpus, and liver and biliary tract) occurred almost as frequently as the number of subsequent nonsimultaneous tumors, which suggests that the patterns of risk over time for certain sites may be distorted when diagnoses are advanced in time and removed from analysis.(ABSTRACT TRUNCATED AT 400 WORDS)

Age Factors↗

Characteristics of prostate cancer in families potentially linked to the hereditary prostate cancer 1 (HPC1) locus.

CONTEXT: Approximately 9% of prostate cancer cases have been estimated to result from inheritance of mutated prostate cancer susceptibility genes. Few data exist as to whether there are clinical differences between prostate cancers that are inherited and those that occur in the general population. OBJECTIVE: To investigate phenotypic characteristics of families potentially linked to the hereditary prostate cancer 1 (HPC1) locus on chromosome 1q24-25. DESIGN: Retrospective case study in which clinical data were extracted from medical and pathological records. FAMILIES: A total of 74 North American families with hereditary prostate cancer. Prostate cancer cases from the National Cancer Data Base were used as a reference population for comparison. MAIN OUTCOME MEASURES: The families were divided into 2 groups: either potentially linked (33 families with 133 men with prostate cancer), and thus likely to be carrying an altered HPC1 gene, or potentially unlinked (41 families with 172 men with prostate cancer), on the basis of haplotype analysis in the region of HPC1. The age at diagnosis of prostate cancer, serum prostate-specific antigen levels, digital rectal examination status, stage, grade, primary treatment of prostate cancers, and occurrence of other cancers were compared between the groups. RESULTS: The mean age at diagnosis of prostate cancer for men in potentially linked families was significantly lower than for men in potentially unlinked families (63.7 vs 65.9 years, respectively, P=.01; mean age at diagnosis in the reference population was 71.6 years). Higher-grade cancers (grade 3) were more common in potentially linked families, and advanced-stage disease was found in 41% of the case patients in potentially linked families compared with 31% in both the potentially unlinked families and the reference groups (P=.03 for the latter comparison). In the other clinical parameters, we found no significant differences between the groups. A modest excess of breast cancer and colon cancer was found in potentially linked families in comparison with potentially unlinked families, but this difference was not statistically significant. CONCLUSIONS: Families that provide evidence for segregation of an altered HPC1 gene are characterized by multiple cases of prostate cancer that, in most respects, are indistinguishable from nonhereditary cases. However, 3 characteristics were observed: younger age at diagnosis, higher-grade tumors, and more advanced-stage disease. Our study shows that a significant fraction of hereditary prostate cancers are diagnosed in advanced stages, emphasizing the clinical importance of early detection in men potentially carrying prostate cancer susceptibility genes. These findings support the current recommendations to screen men with a positive family history of prostate cancer beginning at age 40 years.

Age Factors↗

Thyroid cancer and multiple primary tumors in the SEER cancer registries.

Thyroid cancer incidence rates have increased steadily in the United States and elsewhere. Radiation exposure at a young age is a strong risk factor, but otherwise the etiology is unclear. To explore etiologic clues, we studied the risk of thyroid cancer after an earlier primary cancer, as well as the risk of developing multiple primaries after an earlier thyroid cancer in the U.S. Surveillance, Epidemiology and End-Results (SEER) cancer registries program (1973-2000). In 2,036,597 patients diagnosed with any invasive cancer who survived for a minimum of 2 months, we observed a 42% increased risk compared to the general population for second thyroid cancer based on 1,366 cases (95% confidence interval (CI) = 35-50%; excess absolute risk (EAR) = 0.38/10,000 person-years (PY)). Elevated risks were observed after most cancer sites studied. The most pronounced excess (observed/expected (O/E) = 2.86) was seen for second thyroid cancers detected in the year after diagnosis of the first cancer. Among 29,456 2-month thyroid cancer survivors, 2,214 second cancers occurred (O/E = 1.11, 95% CI = 1.06-1.15; EAR = 7.64/10,000 PY). Again, the highest risk was seen in the first year (O/E = 1.26). Patients <40 years of age at diagnosis of thyroid cancer had a 39% increased risk of a second cancer, whereas for older patients the risk was elevated 6%. We observed consistently increased risks for cancers of the breast, prostate, and kidney, and a likely radiation treatment-related excess of leukemia. Based on small numbers of cases, cancers of the salivary glands, trachea, scrotum, adrenal glands, and brain and central nervous system (CNS) also occurred in excess. A decreased risk was observed for smoking-related malignancies. Thyroid cancer is associated with primary cancers of many different organs. Although enhanced medical surveillance likely plays a role, 2-way, positive associations between thyroid cancer and cancers of the breast, prostate, kidney, salivary glands, brain and CNS, scrotum, and leukemia suggest etiologic similarities and possible treatment effects.

Adult↗

Overview of colorectal cancer in Japan: report from the Registry of the Japanese Society for Cancer of the Colon and Rectum.

BACKGROUND AND PURPOSE: In Japan, the incidence of colorectal cancer has increased remarkably since World War II, and interest in this cancer has grown rapidly among Japanese clinicians and pathologists. As a result, the Japanese Society for Cancer of the Colon and Rectum started a multi-institutional registry of colorectal cancer in 1980. The purpose of this report is to present an overview of the actual state of surgical and pathologic aspects of colorectal cancer treated in the leading hospitals in Japan. MATERIALS AND METHODS: Registry files of clinical and pathologic findings for 38,369 patients treated between 1974 and 1986 with five-year follow-up information and 26,360 patients treated between 1991 and 1994 with no follow-up information were reviewed. RESULTS: Numbers of registered patients have increased annually, reflecting a trend toward an increasing incidence of this cancer in Japan. Colon cancer increased more than rectal cancer in both genders. Resection of the primary lesion was achieved in more than 97 percent of patients who underwent surgical operation recently. The curative resection rate has improved from 65.1 to 79.1 percent for colon cancer and from 71.4 to 80.4 percent for rectal cancer between the 1974 and 1979 and the 1991 and 1994 periods, and operative mortality of those has decreased from 1.8 and 2 percent to 0.5 and 0.5 percent, respectively. There was a trend toward a decrease in locally advanced cancer in terms of cancer invasion into the bowel wall. Stage IV colon cancer also decreased from 22.9 to 16.6 percent with time. The five-year survival rate of each pTNM stage has gradually been improving and was especially evident for patients with Stages I, II, and III of rectal cancer. Overall five-year survival rates for colorectal cancer patients currently exceeds 60 percent. CONCLUSION: The overall incidence of colorectal cancer and the ratio of colon cancer to rectal cancer patients in Japan are increasing. Results of surgical treatment are satisfactory with respect to curative resection rate, operative mortality, and the five-year survival rate. Registry data of the Japanese Society for Cancer of the Colon and Rectum are useful for reporting the actual state of diagnosis, treatment, and end results of colorectal cancer in Japan.

Adenocarcinoma↗

Incidences and trends of second cancers in female breast cancer patients: a fixed inception cohort-based analysis (United States).

OBJECTIVE: To determine incidences and time trends of second cancers among female breast cancer patients. METHODS: Using data of the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) Program, we designed three inception cohorts: 1975-1977 (n=25,920), 1983-1985 (n=32,722) and 1991-1993 (n=40,819), and analyzed their incidences of second cancers during the first 8 years after initial breast cancer diagnosis. RESULTS: Between the 1970s and the 1990s, the incidence rate of malignant second cancer significantly increased among female breast cancer patients, of which second non-Hodgkin's lymphoma and kidney cancer increased by about 150%, while second cancers of the thyroid, uterine corpus and skin melanoma increased 80%, and cancer of the lung increased 50%. The patterns of trend of second cancers were somewhat similar to those of the general population except for second endometrial cancer at all ages and second leukemia and skin melanoma among young patients aged 20-49. In the 1990s, the risk ratios (RR) of all sites cancer were found to be 5.5 (95% CI=5.0-6.1) for age 20-49, 1.3 (1.3-1.4) for age 50-64, and 1.2 (1.1-1.2) for age 65 and over, comparing breast cancer patients to general population. Additionally, radiotherapy slightly increased the risks of second leukemia (RR=1.8, 1.2-2.8), and second endometrial (RR=1.3, 1.0-1.6) and breast (RR=1.2, 1.1-1.3) cancers. CONCLUSIONS: The fixed inception cohort method is valid for analyzing cancer registry-based second cancer data. By this method, we found that the incidence of second cancer has substantially increased among female breast cancer patients over the past 25 years. Observed changes in incidence may partially reflect the effect of treatments. Because the absolute number of affected patients is small, however, the breast cancer treatments have remained safe for most patients.

Adult↗

Non-cancer mortality among people diagnosed with cancer (Australia).

OBJECTIVE: To investigate whether people diagnosed with cancer have an increased risk of death from non-cancer causes compared to the general population. METHODS: The non-cancer mortality of people diagnosed with cancer in Queensland (Australia) between 1982 and 2002 who had not died before 1 January 1993 was compared to the mortality of the total Queensland population, matching by age group and sex, and reporting by standardised mortality ratios. RESULTS: Compared to the non-cancer mortality in the general population, cancer patients (all cancers combined) were nearly 50% more likely to die of non-cancer causes (SMR = 149.9, 95% CI = [147-153]). This varied by cancer site. Overall melanoma patients had significantly lower non-cancer mortality, female breast cancer patients had similar non-cancer mortality to the general population, while increased non-cancer mortality risks were observed for people diagnosed with cervical cancer, colorectal cancer, prostate cancer, non-Hodgkin lymphoma and lung cancer. CONCLUSIONS: Although cancer-specific death rates underestimate the mortality directly associated with a diagnosis of cancer, quantifying the degree of underestimation is difficult due to various competing explanations. There remains an important role for future research in understanding the causes of morbidity among cancer survivors, particularly those looking at both co-morbid illnesses and reductions in quality of life.

Adult↗

Incidence of second primary cancer following testicular cancer.

The incidence of second primary cancers was investigated in 6187 Danish men diagnosed with testicular cancer in the period 1943-1987. During the course of 59,000 person years, 459 subsequent primary cancers occurred. The relative risks were significantly increased for leukaemia, gastric cancer, pancreatic cancer, bladder cancer, non-melanoma skin cancer and kidney cancer. Increased incidence was furthermore suggested for cancer of the rectum, prostate and lung. The increased incidence of leukaemia appeared in the first 10 years after testicular cancer diagnosis. The excess incidence for gastric cancer, pancreatic cancer, rectal cancer and lung cancer was strongest 10-19 years after testicular cancer, while the relative risk of non-melanoma skin cancer and prostate cancer increased throughout the period of follow-up. The increased incidence of cancer in this cohort is most likely an effect of radiotherapy used for testicular cancer. It is proposed that the different incidence patterns over time after testicular cancer diagnosis reflect differences in the growth rate of tumours originating in different tissues.

Adult↗

Gall bladder cancer, extrahepatic bile duct cancer and ampullary carcinoma in New Zealand: Demographics, pathology and survival.

INTRODUCTION: The aim of present paper was to document the incidence of gall bladder cancer, cancer of the extrahepatic bile ducts and ampullary carcinoma in New Zealand. METHODS: Data were collected from the New Zealand Cancer Registry from 1980 to 1997 and combined with national census statistics to give crude and age standardized incidence rates. RESULTS: Over the 18-year study period, 226 carcinomas of the ampulla of Vater, 608 gall bladder cancers, and 486 extrahepatic cholangiocarcinomas were registered. The age standardized incidence rates for gall bladder carcinoma in all New Zealanders were 0.41/100 000 in men and 0.74/100 000 in women. The age standardized incidence rates for gall bladder cancer in Maori were 1.49/100 000 in Maori men and 1.59/100 000 in Maori women. The corresponding age standardized incidence rates for extrahepatic bile duct cancers were 0.67/100 000 in men and 0.45/100 000 in women. There were insufficient cases to calculate an age standardized incidence in Maori or Pacific Islanders. For carcinoma of the ampulla, the age standardized rates were 0.34/100 000 in men and 0.25/100 000 in women. There were insufficient cases to calculate an age standardized incidence rate for Maori or Pacific Islanders. When histology was defined adenocarcinoma was the most common form of cancer occurring in 66% of gall bladder cancers, 91% of extrahepatic bile duct cancers and 70% of ampullary cancers. Most tumours were advanced at presentation with regional or distant metastases present in 72% of gall bladder cancers, 63% of extrahepatic bile duct cancers and 69% of ampullary tumours at diagnosis. Survival was poor with median survivals of 86 days, 151 days and 440 days recorded for gall bladder cancer, extrahepatic bile duct cancer and ampullary cancer, respectively. CONCLUSIONS: The demographic profile, pathology and survival of patients with gall bladder cancer, extrahepatic bile duct cancer and ampullary carcinoma are similar in New Zealand to that of other Western countries. However New Zealand Maori have a relatively high incidence of gall bladder cancer, and the incidence is equal in both Maori men and women, while cancers of the extra-hepatic bile duct and ampulla of Vater are rare in Maori. In comparison, cancers of the gall bladder, extrahepatic bile ducts and ampulla are rare in Pacific Islanders.

Adenocarcinoma↗

Cancer associated with obstetric delivery: results of linkage with the California cancer registry.

OBJECTIVE: This study provides revised population-based measurements for the occurrence rates of cancer associated with obstetric delivery and examines perinatal and cancer-related outcomes within the group of women with 4,846,505 obstetric deliveries in California, inclusive of the years 1991 through 1999. STUDY DESIGN: This observational study used a population-based retrospective review of cases identified as a result of computer linkage of maternal/neonatal hospital discharge and birth/death records with case files in the California Cancer Registry (CCR). The effect of timing of cancer diagnosis on clinical outcomes was studied by dividing the cases into three groups as follows: "prenatal" for cancer diagnosis within 9 months before delivery, "at delivery" for cancer diagnosis during delivery hospitalization, and "post partum" for cancer diagnosis within 12 months after delivery. Computerized records for 4,846,505 obstetric patients and 4,906,920 newborn infants comprising the linked vital statistics birth/patient discharge database (VS/PDD) were used to identity-match cases within the CCR case files. Cases of malignant disease were categorized into 22 anatomic or histologic subgroups. Perinatal clinical outcomes including preterm delivery, prolonged neonatal hospital stay, stillbirth, neonatal death, frequency of first trimester prenatal care, and cesarean delivery were analyzed by use of International Classification of Diseases, 9th Revision, Clinical Modification codes from the VS/PDD. Clinical cancer outcomes including cancer stage and vital status on follow-up were drawn from CCR records. Statistical comparisons for trends were performed with the Cochran-Armitage test, outcomes comparisons with the Fisher exact test, and survival comparisons were performed with the Cox proportional hazard model. RESULTS: Among 4,846,505 obstetric deliveries, 4,539 cases of invasive malignancy were identified for an observed occurrence rate of 0.94 per 1000 births. Sixty-four percent of the cases occurred post partum; cancers of the breast, thyroid, cervix, along with malignant melanoma, and Hodgkin's disease accounted for 64% of the cases. The timing of cancer diagnosis affected clinical outcomes: for all cancer cases as a group, the most favorable perinatal and cancer outcomes occurred in women whose cancer diagnosis was made 6 to 9 months before delivery (6% of cases). The most unfavorable perinatal and cancer outcomes were associated with cancer diagnosis made 0 to 3 months before delivery (14% of cases). For women whose cancer was diagnosed post partum, perinatal outcomes were minimally affected by the presumed existence of occult cancer at the time of obstetric delivery. CONCLUSION: The use of computer-linkage to the CCR files enhanced identification of cases of maternal malignancy associated with obstetric delivery. Cancer diagnosis was associated with approximately 1 in 1000 deliveries. Most cases were diagnosed after delivery and were comprised predominantly of cancers of the breast, thyroid, cervix, malignant melanoma, and Hodgkin's disease. A small group of women (approximately 1 per 5000 deliveries) are seen within a few months before delivery or at delivery with malignant disease, many of whom have rapidly progressing disease and may require high-risk perinatal and oncology services.

Breast Neoplasms↗

Transrectal ultrasound-guided transperineal 14-core systematic biopsy detects apico-anterior cancer foci of T1c prostate cancer.

AIM: The optimal biopsy strategy for prostate cancer detection, especially in men with isolated prostate-specific antigen (PSA) elevation, remains to be defined. We evaluated diagnostic yield and safety of transrectal ultrasound (TRUS)-guided transperineal systematic 14-core biopsy and compared the spatial distribution of cancer foci detected with this technique in men with and without abnormality on digital rectal examination (DRE). METHODS: In a prospective study, 289 men aged between 50 and 87 years (median age, 70 years) underwent TRUS-guided transperineal systematic 14-core prostate biopsy because of elevated PSA and/or abnormal DRE findings. Using the fan technique, 12 cores from the peripheral zone and two cores from the transition zone were obtained systematically. To characterize the spatial distribution of cancer positive cores, site-specific overall and unique cancer detection rates were compared between stage T1c and T2 cancers. RESULTS: Prostate cancer was detected in 105 of the 289 patients (36%). Major complications requiring prolonged hospital stay or re-hospitalization during a 4-week postbiopsy period were rare (1.4%). Sixty-seven stage T1c cancers were identified. These cancers were associated with significantly lower PSA and a smaller number of cancer positive cores when compared with stage T2 cancers (n= 38). The overall cancer detection rate was highest at the anterior peripheral zone and the posterior peripheral zone in stage T1c and stage T2 cancers, respectively. The unique cancer detection rate at the anterior peripheral zone was significantly higher in stage T1c cancers than in stage T2 cancers. Therefore, when the prostate is extensively biopsied using the transperineal approach, cancer positive cores are characteristically distributed anteriorly in stage T1c cancers and posteriorly in stage T2 cancers. CONCLUSIONS: TRUS-guided transperineal systematic 14-core biopsy showed an apico-anterior distribution of cancer foci in stage T1c prostate cancers.

Aged↗