Oesophageal cancer associated with other primary cancers: a study of 31 patients

The aim of this study was to investigate the characteristics of oesophageal cancer associated with other primary cancers and the survival rate after surgery for the patients with these cancers. Of 202 patients with oesophageal cancer treated in the Second Department of Surgery, Shinshu University School of Medicine between 1981 and 1995, 31 patients (15.3%) had oesophageal cancer associated with other primary cancers. Twenty-one synchronous and 10 metachronous associated cancers were found and 25 of them were resected. Early-stage oesophageal cancer was much more frequent in the associated cases than in the non-associated cases. The stomach was the most frequently associated organ. The numbers of cases with triple and quadruple cancers were three and one, respectively. Three of these cases had intervals of over 6 years between tumours. Three cases with other primary cancers which had intervals of over 7 years after oesophagectomy were found, and two were carcinomas of the reconstructed gastric tube. In the outcome after surgery for oesophageal cancer, there was no difference between the associated and the non-associated cases, and also no difference between the synchronous and metachronous associated cases. Regarding the five-year and 10-year survival rates after surgery for the first cancers, the synchronous cases had a poorer outcome than did the metachronous cases. In conclusion, oesophageal cancer with other primary cancers is not always rare, and its outcome is not poor compared with that of the non-associated cases. These patients may achieve survival by early detection of both lesions and positive treatment. It is important to consider the risk of other primary cancers after oesophagectomy, and the success of the reconstructed gastric tube should be followed by endoscopy.     

Establishment of a hereditary nonpolyposis colorectal cancer registry

INTRODUCTION: Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominant condition characterized by early age of onset colorectal cancer, right-sided predominance, excess of synchronous and metachronous colonic neoplasms, and extracolonic cancers. The purpose of this study is to report clinical characteristics of HNPCC families in our registry. METHODS: This is a retrospective review of medical records of patients with a significant history of colorectal cancer and interviews with their families. RESULTS: Three hundred one people with cancer in 40 HNPCC families were identified. In 284 of 301 (94 percent) people, 363 cancers were identified. Colorectal cancer only was identified in 182 people (64 percent) and, in conjunction with extracolonic tumors, in another 31 people (11 percent). Extracolonic cancer alone was noted in 71 people (25 percent). Median age at diagnosis of colorectal cancer was 48 (range, 17-92) years. In patients with documented pathology, right-sided tumors predominated (55 percent), synchronous and metachronous tumors were noted in 53 percent, and synchronous of metachronous adenomas were documented in 51 percent of people. Generational anticipation was also noted. CONCLUSION: This study demonstrates and confirms characteristics that have been described in HNPCC. Namely, early age of onset of colorectal cancer, right-sided predominance, multiple synchronous and metachronous neoplasms, increased extracolonic cancers, and generational anticipation.     

A sensitive assay for studying dopaminergic activity in cultures of rat pituitary cells

Nine male patients with separate primary cancers of the esophagus and head and neck (pharynx, larynx) presented with a mean age of 56 years (41-69). They included 7 pharyngeal cancer patients and 2 laryngeal ones. Esophageal cancer was discovered synchronously in 6 patients and metachronously in 3 (1, 4, and 11 years later, respectively). The head and neck cancer was stage-I in one patient, stage-II in 4 and stage-IV in 4. The esophageal cancer was cervical in 2, thoracic in 6 and abdominal in 1. It was early cancer (stage-0) in 6 patients and advanced (stage-IV) in 3. The esophageal cancer was more advanced in the metachronous group, while it was early in the synchronous group. Since the head and neck cancer was advanced, all patients underwent a total laryngectomy for their head and neck cancers. As for esophageal surgery, a transhiatal esophagectomy was, in principle, performed for early cancers while a total thoracic esophagectomy was done for advanced cancers. For the reconstruction of the esophagus, a gastric tube was used. Four patients are still alive with a mean survival time of 25 months, whereas five died of cancer recurrence of either type a mean of 19 months after surgery. As compared with the survival rates of the patients with esophageal cancer alone, the 5-year survival rate was 18.2% for patients with double cancers in this series and 27.9% for those with esophageal cancer alone.     

Outcome after multiple colorectal tumours

BACKGROUND: Patients with primary colorectal cancers have a higher risk of development of second tumours synchronously or metachronously. This special group of patients raise a particular interest in their characteristics and outcome. METHODS: The records of 1009 patients with colorectal cancer were scrutinized. A group with multiple cancers was identified. Perioperative investigations, patterns of follow-up, pathological variables and outcome were noted. RESULTS: There were 22 patients with metachronous tumours and 39 with synchronous tumours following 'curative' operations in 20 and 28 respectively. There was no difference in Dukes classification between the two groups: Polyps were associated with metachronous lesions in ten of 22 patients and synchronous lesions in 17 of 39 patients. Five-year survival was 75 per cent for patients with metachronous tumours and only 18 per cent for those with synchronous tumours. CONCLUSION: In this study patients with metachronous tumours seemed to do very well while those with synchronous lesions did very badly. There were no identifiable demographic or clinical characteristics to account for this. There is a need to study this group of patients and identify factors like tumour biology or host resistance which prevent spread of tumour.     

Development of synchronous bilateral lung cancers after esophagectomy for esophageal cancer: report of a case

It is well known that squamous cell carcinoma of the esophagus can be associated with carcinoma of other organs. We report herein the rare case of a 60-year-old man who developed synchronous bilateral lung cancers after undergoing esophagectomy for esophageal cancer. Staged bilateral lobectomy was successfully performed to minimize respiratory complications 3 years after his esophagectomy. This case report serves to demonstrate that aggressive and careful surgical approach with adequate followup offers the chance of long-term survival for patients with multiple primary cancers.     

Association of non-acquired immunodeficiency syndrome-defining cancers with human immunodeficiency virus infection

Kaposi's sarcoma and non-Hodgkin's lymphoma were among the earliest recognized manifestations of the acquired immunodeficiency syndrome (AIDS) epidemic. Excluding these two tumors, the overall risk of all other cancers in human immunodeficiency virus (HIV)-infected individuals is similar to that of the general population. However, varying levels of evidence link several additional neoplasms to HIV infection. The evidence is strongest for an association with Hodgkin's disease, with lower relative and absolute risks than for non-Hodgkin's lymphoma. Anogenital intraepithelial neoplasia also appears to be HIV associated, but increases of invasive disease are still uncertain for both cervical and anal cancers. Various studies have suggested associations with testicular seminoma, multiple myeloma, oral cancer, and melanoma, but the data are inconsistent. Leiomyosarcoma and benign leiomyomas have increased in incidence in HIV-infected children but are unusual in HIV-infected adults. Conjunctival carcinoma is seen in HIV-infected individuals in sub-Saharan Africa but it is uncommon in Western countries. Most other cancers do not seem to have increased incidences in HIV infection. The etiologic mechanisms of HIV-related cancer likely differ among these diverse cancers and do not globally increase cancer risk.     

Synchronous primary carcinoma of the colon. Diagnostic and therapeutic problems

Seven hundred and twenty-three patients with colorectal carcinoma were treated consecutively from November 1973 to April 1997. Seven patients (0.96%) were found to have two colorectal carcinomas (synchronous carcinoma), located in separated colonic areas. Clinical histories were analyzed with reference to sex, age, symptoms, physical findings, disease localization, pathologic classification, and survival data. Preoperative diagnosis of synchronous lesions is difficult, being achieved in only 2 cases, but it is important for the proper treatment of patients. It is concluded that full examination of the colon in all patients presenting with primary colorectal cancer is mandatory and that colonoscopy should be used to effectively screen patients for synchronous cancers.     

Loss of heterozygosity and mutational analysis of the PTEN/MMAC1 gene in synchronous endometrial and ovarian carcinomas

Mutations of the human putative protein tyrosine phosphatase (PTEN/MMAC1) gene at chromosome 10q23 have been found frequently in type I endometrial carcinomas. Endometrioid adenocarcinoma is the most frequent histology seen in patients with clinically determined synchronous endometrial and ovarian carcinomas. We report a high incidence of PTEN/MMAC1 mutations and 10q23 loss of heterozygosity (LOH) in patients with synchronous endometrial and ovarian carcinomas. Paraffin-embedded precision microdissected tumors were analyzed for 10 matched synchronous endometrial and ovarian cancers and 11 matched control metastatic endometrial cancers. Single-stranded conformation polymorphism analysis was used to screen for mutations in all tumors and corresponding normal lymphocyte DNA. LOH was determined using a panel of four microsatellite markers within the PTEN/MMAC1 locus. PTEN/MMAC1 mutations were found in 43% (9 of 21) of the endometrial cancers studied, similarly represented in the clinically synchronous group (5 of 10 or 50%) and the advanced metastatic group (4 of 11; 36%; P = 0.53). In two of the five cases of clinically synchronous cancers, identical or progressive PTEN mutations were found in both the endometrial and ovarian cancers, suggesting that the ovarian tumor is a metastasis from the endometrial primary. PTEN/MMAC1 mutations in the advanced endometrial cancers were similar in the corresponding metastases. In one case, the mutation was seen in only one of two metastatic lymph nodes. The LOH analysis demonstrated 55% LOH in at least one PTEN/MMAC1 marker. These findings suggest that the putative tumor suppressor gene PTEN/MMAC1 may be a viable molecular marker to differentiate synchronous versus metastatic disease in a subset of clinically synchronous endometrial and ovarian carcinomas.     

Second primitive malignant tumour in patients with gynaecological cancer

OBJECTIVE: The purpose of this study was to characterise the occurrence of multiple primitive gynaecological malignant neoplasias, restricted to the genital tract and breast or associated with other organs, and to detect which types of association are most frequent concerning location, histology and staging. POPULATION AND METHODS: The records of patients with gynaecological cancer at the Portuguese Institute of Oncology--Lisbon Centre, between 1986 and 1993 were used in this study. RESULTS: Of the 10,746 women with gynaecological cancer, 91 (0.8%) were found to have a second primitive malignant neoplasia. Of these neoplasias, 64% (58 cases) were also located at a gynaecological site. The most frequent associations were endometrium/breast (13 cases), bilateral breast (12 cases) and ovary/endometrium (11 cases). The majority of primitive multiple gynaecological tumours were synchronous. Regarding gynaecological cancer and non-gynaecological cancer, in 28 cases (31%), the most common non-gynaecological location was the colon/rectum. Five patients had triple tumours. CONCLUSION: Although these situations are relatively rare the possibility of multiple primitive cancers should be considered with the presence of malignant tumours in two or more organs. This distinction between multiple primitive or metastatic cancers could be important for treatment as well as prognosis.     

D2 receptor binding in dopa-responsive dystonia

OBJECTIVES: Synchronous gastric tumors (including benign and secondary tumors) associated with esophageal cancer present diagnostic and therapeutic issues. We investigated this synchronous association, and retrospectively determined the frequency of the gastric tumors and the clinical characteristics. METHODS: In a series of 208 patients with esophageal cancer, we investigated the synchronous gastric tumors, as well as the frequency of association, clinicopathological characteristics, diagnosis, treatment, and the clinical outcome after surgery. RESULTS: Twenty-eight gastric tumors were found in 24 patients. Adenocarcinoma was most frequent. Most of these tumors were located at the upper or middle third of the stomach. Eight gastric tumors in six patients could not be detected preoperatively. Six of these tumors including a gastric remnant cancer were detected in the resected stomach, and two leiomyomas were detected during the operation. In one patient in which an endoscope could not pass through the esophagus, a leiomyoma was detected in the resected stomach. For the gastric cancers, total gastrectomy or proximal gastrectomy with lymph node dissections was performed. For the benign tumors, partial resection of the stomach was performed, and endoscopic resection was performed preoperatively for an adenoma. In both the postoperative hospital mortality rate and the survival rate after surgery, there were no significant differences between the patients with and without gastric tumors. CONCLUSIONS: Synchronous gastric tumors associated with esophageal cancer are not rare. When an endoscope cannot pass through the esophagus before surgery, other techniques must be performed to explore the stomach. For these patients, surgical treatment should be adapted positively.     

Synchronous hepatocellular carcinoma or metastatic hepatic tumor with primary gastric cancer

BACKGROUND/AIMS: When a solitary hepatic tumor occurs synchronously with gastric cancer, it is usually presumed to be metastatic. However, this may not be true in a place like Taiwan, where hepatocellular carcinoma (HCC) is prevalent. This study was conducted to examine the clinicopathological factors of both conditions. METHODOLOGY: A retrospective analysis of 14 patients who underwent a synchronous hepatectomy in combination with radical gastrectomy over the past 15 years was performed. RESULTS: Seven patients had metastatic gastric cancer, and seven had concomitant gastric and hepatic cancer. Serosal invasion and lymph node metastasis were the major features in the patients with metastatic gastric cancer. Early gastric cancer was found in three of the patients with the coexisting primary cancers. No patient with solitary metastatic cancer survived more than one year, but long-term survival of more than two years was achieved in two patients with the two forms of cancer. CONCLUSIONS: Double cancer of the stomach and liver should be kept in mind in patients with gastric cancer concomitant with a solitary hepatic tumor, in order to provide optimal treatment.     

Morphological and functional aspects of the cardiovascular system related to aging: does "aging heart" exist?

Thromboembolic disease (TE) is an important cause of in-hospital morbidity and mortality. The relationship between cancer and abnormalities of blood coagulation has been recognized for well over a century. Deep venous thrombosis (DVT) of the lower extremities is the most common cause of thromboembolic disease, but pulmonary embolism, upper extremity vein thrombosis, disseminated intravascular coagulation, and other, more unusual, clinical events, may occur. Unexplained TE may serve as a marker for the presence of a hidden tumor. The frequency of pulmonary embolism (PE) among patients with a malignant neoplasm at necropsy is highly increased in the elderly patients. Among subjects with a malignant neoplasm, patients with pancreatic and gastric cancer (mucin-secreting adenocarcinomas), cancer of the large bowel and women with ovarian cancer had the highest frequency of PE. Old age, female sex, gastrointestinal and ovarian cancers must be considered as a significant risk factor for PE. The potentially responsible mechanisms for the thrombotic events, clinical manifestations, diagnostic implications and aspects of treatment of TE in malignant disease are discussed.     

Can knee joint proprioception by reconstruction of the anterior cruciate ligament be restored? A prospective longitudinal study

BACKGROUND: Usual ductal hyperplasia (UDH), atypical ductal hyperplasia (ADH), and ductal carcinoma in situ (DCIS) are risk factors for invasive breast cancer (IBC), suggesting that these lesions may be direct precursors of IBC. To identify genetic changes that may be important in the early development of precursor lesions and their progression to malignant or invasive disease, we examined 399 putative precursors (211 UDH, 51 ADH, 81 non-comedo DCIS, and 56 comedo DCIS) for loss of heterozygosity (LOH) at 15 polymorphic genetic loci known to exhibit high rates of loss in IBC. We also assessed the sharing of LOH by putative precursors and synchronous cancers. METHODS: The polymerase chain reaction was used to analyze DNA from microdissected archival specimens. RESULTS AND CONCLUSIONS: In hyperplasias from noncancerous breasts (i.e., without DCIS and/or IBC in analyses of hyperplasias), LOH at any given locus was rare (range, 0%-15%), although 37% of UDH and 42% of ADH lesions showed loss for at least one locus, suggesting that the development of hyperplasias can involve many different tumor suppressor genes. In DCIS from noncancerous breasts (i.e., without IBC in analyses of DCIS), LOH was common, with 70% of noncomedo lesions and 79% of comedo lesions showing at least one loss. In DCIS, substantial rates of loss (up to 37%) were observed at loci on chromosomes 16q, 17p, and 17q, suggesting that inactivated tumor suppressor genes in these regions may be important in the development of noninvasive breast cancer. When DCIS lesions from cancerous and noncancerous breasts were compared, substantially more LOH was observed in the cancerous breasts at a few loci (on chromosomes 2p, 11p, and 17q), suggesting that genetic alterations in these regions may be important in the progression to invasive disease. Among specimens harvested from cancerous breasts, 37% of UDH, 45% of ADH, 77% of noncomedo DCIS, and 80% of comedo DCIS lesions shared LOH with synchronous cancers at one locus or more, supporting the idea that the putative precursors and the cancers are genetically related.     

Cancers related to tobacco smoking

Tobacco smoking is the major cause of lung cancer. Cigarette smokers have a risk of lung cancer 10 to 15 times greater than nonsmokers. Tobacco and alcohol are the main risk factors for cancers of oral cavity, larynx, pharynx and oesophagus (cancers of the upper respiratory and upper digestive tract) and the effects of tobacco and alcohol are multiplicative. For these cancers, the risk associated with tobacco was about 2 to 4 among people who drink little or no alcohol. Risks of lung cancer and of cancers of the upper respiratory and upper digestive tract increase with an increasing number of cigarettes smoked per day and duration of smoking. Tobacco is also a risk factor for bladder cancer. Cigarette smoking is a possible contributory factor in the development of kidney, pancreatic and cervical cancers. Among males, lung cancer mortality increased regularly over time and today, lung cancer is the leading cause of death and illness from cancer. Substantial reductions in the number of deaths from tobacco-related cancers could be achieved if a large proportion of smokers stopped smoking.     

Molecular epidemiology of breast cancers in northern and southern Japan: the frequency, clustering, and patterns of p53 gene mutations differ among these two low-risk populations

Comparison of acquired mutations in the p53 tumor suppressor gene can illuminate factors contributing to carcinogenesis among cancer cohorts. Japan has an ethnically homogeneous population with a low incidence of breast cancer. Previously we reported an unusual frequency, allelic status, and clustering of mutations in breast cancers from the northern part of the main Japanese island. To extend these findings, exons 2-11 and adjacent intronic sequences were analysed in tumors of women from northern (Hokkaido) and southern (Tokushima) Japan. The frequency of breast cancers with p53 gene mutations in the Hokkaido group is the highest reported (81%) while that in Tokushima (28%) is similar to most other populations. Thirteen of the 19 mutations (68.4%) in the Hokkaido cohort were heterozygous, an unusually high frequency for p53 mutations in any tumor type. There were three missense mutations at codon 175, a known hotspot for alterations in the p53 gene, and three missense mutations at codon 179, a rare site for p53 changes. In addition, the patterns of p53 gene mutation differed between the two Japanese cohorts (P=0.04). The multiple differences in acquired p53 mutations suggest unsuspected biological differences among breast cancers in northern and southern Japan. In addition, the high frequency of p53 mutations in breast cancers from Hokkaido predicted a poorer prognosis for this population which was confirmed on examination of mortality data.     

Multicentric primary adenocarcinomas of the midgut: the first case report

Multicentric adenocarcinomas of the midgut have not been described; even multiple adenocarcinomas limited to the small intestine are extremely uncommon, with only 14 cases reported in the literature. We report a case of multicentric synchronous involvement of the entire midgut with adenocarcinoma in a 52-yr-old Polish woman who had more than 30 lesions extending from duodenum to mid-transverse colon. There was no family history of cancer. Preoperative evaluation and intraoperative exploration were negative for primary malignancy of the lungs, breasts, ovaries, pancreas, and other parts of the gastrointestinal tract. Results of histopathological examination, immunohistochemical staining, and ras mutational analysis of the lesions uniformly support the diagnosis of multicentric poorly differentiated adenocarcinoma. The cause for this unusual presentation is unknown, although sporadic genetic alteration(s) of oncogene(s) might have been the precipitating event.     

Estimates of the worldwide incidence of eighteen major cancers in 1985

The annual incidence rates (crude and age-standardized) and numbers of new cases of 18 different cancers have been estimated for the year 1985 in 24 areas of the world. The total number of new cancer cases (excluding non-melanoma skin cancer) was 7.6 million, 52% of which occur in developing countries. The most common cancer in the world today is lung cancer, accounting for 17.6% of cancers of men worldwide, and 22% of cancers in men in the developed countries. Stomach cancer is now second in frequency (it was slightly more common than lung cancer in 1980) and breast cancer--by far the most important cancer of women (19.1% of the total)--is third. There are very large differences in the relative importance of the different cancers by world area. The major cancers of developed countries (other than the 3 already named) are cancers of the colon-rectum and prostate, and, in developing countries, cancers of the cervix uteri, mouth and pharynx, liver and oesophagus. The implications of these patterns for cancer control, and specifically prevention, are discussed. Tobacco smoking and chewing are almost certainly the major preventable causes of cancer today.     

Cutaneous gangrene secondary to metastatic calcification in end stage renal failure--a case report

The belief that oestrogens are involved in the pathogenesis both of testicular cancer in young men and of cancers of the endometrium and female breast has become widespread. In a search for possible hormonal links between these cancers, we investigated the cancer pattern in a cohort of women who had given birth to sons who developed testicular cancer. Particular focus, was given to oestrogen-related cancers. The present retrospective population-based cohort study is based on data from the Danish Cancer Registry. Mothers of 2,204 testicular-cancer patients were followed for the occurrence of cancer over a total of 70,063 person years. The ratio of observed cancers in the cohort over the expected numbers based on cancer incidence in the underlying female population served as measure of the relative risk (RR). The RR of developing breast cancer among mothers of testicular-cancer patients was 0.8 (95% confidence interval 0.6-1.1), the relative risk of endometrial cancer 0.6 (0.3-1.0) and of ovarian cancer 1.0 (0.6-1.6). Mothers of testicular-cancer patients are not at increased risk of developing oestrogen-related cancers.     

The global burden of cancer

The number of new cancer cases, and the annual incidence rates, of 25 different cancers have been estimated for the year 1990 for every country of the world. The distributions of the most common cancers in men and women are presented for 23 broad 'Areas'. The total number (excluding non-melanoma skin cancer) was 8.1 million, just over half of which occur in the developing countries. The most common cancer is lung cancer, which accounts for 18% of cancers of men worldwide. Stomach cancer is second in frequency (almost 10% of all new cancers) and breast cancer--by far the most important cancer of women (21% of the total) is third. There are very large differences in the relative importance of the different cancers by world area; some of the factors, environmental and genetic, underlying the geographic distributions, are discussed.     

Multiple primary cancers in families with Li-Fraumeni syndrome

BACKGROUND: Li-Fraumeni syndrome is a dominantly inherited disorder characterized by early-onset breast cancer, sarcomas, and other cancers in children and young adults. Members of families with this syndrome also develop multiple primary cancers, but the frequency is unknown. To approach this issue, we quantified the incidence of second and third primary cancers in individuals from 24 Li-Fraumeni kindreds originally diagnosed with cancer during the period from 1968 through 1986. METHODS: The relative risk (RR) of subsequent cancers and 95% confidence intervals (CIs) were calculated by use of population-based incidence data from the Connecticut Cancer Registry. Kaplan-Meier analysis was used to determine the cumulative probability (+/- standard error) of subsequent cancers. RESULTS: Among 200 Li-Fraumeni syndrome family members diagnosed with cancer, 30 (15%) developed a second cancer. Eight individuals (4%) had a third cancer, while four (2%) eventually developed a fourth cancer. Overall, the RR of occurrence of a second cancer was 5.3 (95% CI = 2.8-7.8), with a cumulative probability of second cancer occurrence of 57% (+/- 10%) at 30 years after diagnosis of a first cancer. RRs of second cancers occurring in families with this syndrome were 83.0 (95% CI = 36.9-187.6), 9.7 (95% CI = 4.9-19.2), and 1.5 (95% CI = 0.5-4.2) for individuals with a first cancer at ages 0-19 years, 20-44 years, and 45 years or more, respectively. Thirty (71%) of 42 subsequent cancers in this group were component cancers of Li-Fraumeni syndrome. CONCLUSIONS: Compared with the general population, members of Li-Fraumeni syndrome families have an exceptionally high risk of developing multiple primary cancers. The excess risk of additional primary cancers is mainly for cancers that are characteristic of Li-Fraumeni syndrome, with the highest risk observed for survivors of childhood cancers. Cancer survivors in these families should be closely monitored for early manifestations of new cancers.