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PubMed2003

Cancer survival in Sweden 1960-1998--developments across four decades.

This paper summarizes a comprehensive study of cancer survival in Sweden from 1960 to 1998. A total of 1021421 persons and 40 different cancer sites were included in the analyses. The main outcome measure is the relative survival rate (RSR) for different sites and follow-up times after diagnosis. The 10-year RSR for all sites combined has increased steadily-from 26.6% among men and 41.8% among women in the 1960s, to 44.6% (men) and 57.6% (women) in the 1990s. The expectation of life for a person diagnosed with cancer today is about 7 years longer than that of one diagnosed during the mid-1960s. About 3 years are gained due to changes in the relative distribution of various cancer types and about 4 years due to improved relative survival. During the 1990s substantial survival improvements were observed not only for uncommon types, such as testicular cancer, Hodgkin's lymphoma and some other haematologic malignancies, but also for cancer of the rectum, kidney and malignant melanoma. Survival for breast and cervical cancer also improved during the 1990s, but not that for pancreatic, liver or lung cancer.

Age Factors↗
PubMed1983

Gastrointestinal cancer mortality in New Jersey counties, and the relationship with environmental variables.

The State of New Jersey (NJ) USA has been thought to have an unusually high cancer mortality rate; this assumption has been based on 1950-1969 mortality data for its 21 counties. This paper presents an analysis of gastrointestinal (GI) cancer mortality rates in New Jersey counties during 1968-1977, a comparison with the 1950-1969 rates, and associations between current GI cancer mortality rates and selected environmental variables. Age-adjusted mortality rates for GI cancers were calculated for the 21 NJ counties during the period 1968-1977, and were compared with the period 1950-1969, with the Surveillance, Epidemiology and End Results (SEER) survey and with cancer mortality in the US, 1973-1977. The county rates were also correlated with: the distribution of chemical toxic waste disposal sites; annual per capita income; the rates of low birth weight, birth defects, and infant mortality; chemical industry distribution; percentage of the population employed in chemical industries; the density of population; and the urbanization index for each of the counties. Some of the major findings are: Age-adjusted GI cancer mortality rates (all sites combined) were higher than national rates in 20 of 21 NJ counties. In comparison with national trends, NJ stomach cancer rates have declined less, oesophageal cancer rates have declined more, and pancreatic cancer mortality rates have followed similar patterns. Cancer mortality rates in NJ during the period 1968-1977 significantly (p less than 0.0001) exceeded national rates for cancer of the oesophagus (white male, non-white male), stomach (men and women), colon (white male, white female, non-white female), and rectum (whites only). In 18 of the 21 NJ counties, the observed number of cancer deaths for at least one GI cancer site was significantly greater than expected at the 0.0001 level for at least one population subgroup. Among white men, a significant (p less than 0.0001) excess of observed over expected cancer deaths was observed for three or more GI cancer sites in seven counties. The environmental variables that were most frequently associated with GI cancer mortality rates (except pancreatic cancer) were degree of urbanization, population density, and chemical toxic waste disposal sites. Some of the implications of the study findings are discussed and recommendations made for future investigations.

Adult↗
PubMed1980

Incidence of digestive tract cancers in a well defined population in France.

A systematic registration of mortality and morbidity from digestive tract cancers was started in January 1976 in the French department of Cote d'Or (population 455,727). In the course of 3 years 1356 newly diagnosed cases were recorded. In males cancer of the rectum is the most common digestive tract cancer, coming before cancer of the stomach and cancer of the colon. In females cancer of the colon prevails over cancer of the rectum and cancer of the stomach. The survey allows comparison with the incidence rate of digestive cancers in other countries. Results of treatment underline the lateness of diagnosis.

Colonic Neoplasms↗
PubMed1991

A phase I study of a combination of allopurinol, 5-fluorouracil and leucovorin followed by hydroxyurea in patients with advanced gastrointestinal and breast cancer.

Twenty patients with advanced carcinomas of the colorectum, pancreas, stomach, and breast were enrolled in a Phase I study of a sequential administration of 5-fluorouracil-leucovorin (FU-LV) combination followed by hydroxyurea (HU) with allopurinol protection (HALF regimen). As a weekly regimen for 6 weeks, followed by a rest period of 2 weeks, FU was administered intravenously (i.v.) during infusion of a 2-hour i.v. infusion of LV at a dose of 500 mg/m2. Six hours following the FU-LV combination, HU (1 gm/m2) was administered orally. Allopurinol (300 mg every 8 hours, orally) was given the day before and on the day of the administration of the FU-LV combination. The starting dose of FU was 300 mg/m2, with escalations to 900 mg/m2. Mucositis, diarrhea, and hematologic toxicities were mild and sporadic with FU doses up to 750 mg/m2 and occurred in patients who had received prior treatment with FU and/or radiotherapy. Dose-limiting neurocerebellar toxicity was observed in 2 out of 6 patients who received a FU dose of 900 mg/m2. Three additional patients experienced moderate neuromotor toxicity at this dose level. Among 17 patients evaluable for response, partial responses were seen in 3 of the 9 patients with colorectal cancer, 1 of the 3 patients each with carcinoma of breast and pancreas. Three of the 5 responses occurred in patients who had received prior treatment with FU and/or radiation therapy. An FU dose of 750 mg/m2 is recommended for a Phase II trial of the HALF regimen.

Aged↗
PubMed1986

Pylorus-preserving pancreatoduodenectomy. A clinical and physiologic appraisal.

Since 1978, 252 patients from different centers in the world have undergone pylorus-preserving pancreatoduodenectomy. Fifty-five per cent of the patients had malignant tumors in the region of the head of the pancreas. The overall operative mortality rate was 2.8%. Anastomotic leakage and fistulae occurred in 19% of the patients. Pancreatic, biliary, and enteric fistulae represented 11%, 4%, and 4%, respectively. Peptic ulcers were subsequently diagnosed in seven patients (3%), two of whom required vagotomy and antrectomy. Delayed recovery of gastric function was the most common complication of this operation, with an overall incidence of 30%. Although the cause of this gastric dysfunction is unknown, its transient nature in most patients makes expectant therapy with gastric tube drainage the best remedy when the problem is encountered. Pylorus-preserving pancreatoduodenectomy decreased the incidence of postgastric surgery syndromes that are commonly associated with the standard Whipple operation. The existing data support the continued use of the operation and the need for future laboratory and clinical investigation of its physiologic impact.

Adenocarcinoma↗
PubMed1991

Cell kinetics of gastrointestinal tumors after different nutritional regimens. A preliminary report.

Forty-four cases of different untreated gastrointestinal tumors were studied with regard to cell kinetic activity. As a pilot experiment, we also determined the 3H-TdR Labeling Index (LI) in 28 patients in basal conditions and after 15 days of nutritional manipulation with prevalently lipid-based or glucose-based feeding to ascertain whether selective nutritional regimens could affect tumor proliferation. Preliminary results from this study indicate that a kinetic perturbation is induced in tumor cells by nutritional manipulation. Lipid-based feeding seems to produce effects similar to those of chemical or physical anticancer agents, thus suggesting a possible supporting role of nutritional manipulation in cancer treatment strategy.

Aged↗
PubMed1998

Detection of recurrent malignant melanoma with 99mTc-MIBI scintigraphy.

Initial reports suggest that 99mTc-methoxyisobutylisonitrile (MIBI) scanning may be of clinical value in staging patients with malignant melanoma. We carried out a study to evaluate the potential of this technique in the detection of recurrent disease. Whole-body 99mTC-MIBI scans were performed in 81 patients with a history of a surgically excised MM: 28 with known recurrent lesions and 53 during follow-up without evidence of disease. Images started 10 min post-injection, using a dose of 740 MBq. Diagnoses were confirmed by cytological/histological examination or at least one conventional imaging modality. Blinded interpretations of the MIBI scans were performed. Whole-body MIBI scanning correctly detected 68 (92%) of 74 metastatic lesions in the following sites: regional lymph nodes (n=23), non-regional lymph nodes (n=10), skin (n=16), brain/cerebellum (n=6), lung (n=8), bone (n=4) and breast (n=1). The technique failed to detect three subcutaneous regressive lesions (< 1 cm), one liver metastasis, one spleen metastasis and a case of multiple small lesions of the duodenal mucous membrane. In 14 patients the procedure detected previously unknown metastatic lesions. These results suggest that 99mTc-MIBI scanning is an effective imaging modality for whole-body screening of metastatic disease in malignant melanoma patients with the potential to influence treatment planning.

Adult↗
PubMed1994

Comparison of cancer mortality trends in major European areas, 1960-89.

In the prospect of a political and economic 'harmonization' of the European Economic Community (EEC) and, possibly, all Europe, the identification of differences in cancer frequencies and trends in major European areas (ie EEC, non-EEC western countries, and eastern European countries) can help to set health priorities. From 1960-64 to 1985-89 all-age mortality rates of some common cancers (mouth or pharynx, pancreas, lung, kidney, prostate and skin) increased substantially especially in East Europe. Conversely, mortality rates from cancer of the stomach, uterus, testis and from Hodgkin's disease declined, but, again, trends in East Europe were less favourable. Some elevations in rare malignancies (non-Hodgkin's lymphomas, multiple myeloma and connective and soft-tissue sarcomas) emerged rather uniformly in Europe, especially in elderly people. Most favourable trends in total cancer mortality were apparent among females in the EEC (minus 7%) and non-EEC western countries (minus 14%). The picture becomes gradually less favourable with respect to non-EEC western European males and eastern European females (virtually no change) and EEC males (plus 13%). With a 25% increase in total cancer mortality rates in the past 30 years, males in East Europe emerge as the 'problem' group. The even wider gap between West and East Europe in cancer rates in young males leaves no hope for future improvements in the absence of effective interventions. Raising public awareness (especially with respect to smoking and alcohol consumption), and increasing motivation and quality controls among health professionals are badly needed in disadvantaged European areas.

Adult↗
PubMed2000

Surgical and interventional palliative treatment of upper gastrointestinal malignancies.

Malignancies of the upper gastrointestinal tract, including the oesophagus, stomach, liver, bile ducts and pancreas, are highly virulent diseases. While curative therapies relieve symptoms caused by these cancers, most of these treatments prove unsuccessful in the control of tumour due to occult residual disease. This review covers only planned palliative procedures for these conditions where patient factors (e.g. performance status or patient wishes) or tumour factors (e.g. locally advanced or known metastatic disease) prevent potentially curative intervention. For most patients, palliation of luminal obstruction, pain or other symptoms is the most worthwhile treatment that can be offered with present therapies.

Bile Duct Neoplasms↗
PubMed2000

Evaluation of the reliability of chromosomal imbalances detected by combined use of universal DNA amplification and comparative genomic hybridization.

Comparative genomic hybridization (CGH) analysis of microscopic tumor samples is allowed by universal DNA amplification using degenerate oligonucleotide primed-PCR (DOP-PCR). To evaluate the reliablity of DOP-PCR CGH, we performed DOP-PCR CGH and standard CGH in parallel using DNAs extracted from 10 malignant tumors of the hepatobiliary tract and pancreas. Similar results were obtained by both methods with a few exceptions, indicating that DOP-PCR CGH provides cytogenetic information equivalent to that obtained from standard CGH. We also investigated the sensitivity of DOP-PCR CGH using sequential dilutions of DNA from microdissected tumor cells. DOP-PCR using 100 to 800 pg of template DNA yielded successful CGH results. However, less than 50 pg of template DNA was not suitable because of the small amount of generated DNA. These findings suggest that DOP-PCR CGH is applicable for CGH analysis of tiny specimens which are too small for standard CGH. Accordingly, DOP-PCR CGH analysis may become a useful method in clinical laboratory examination.

Aged↗
PubMed2005

Trends in the management and survival of digestive tract cancers among patients aged over 80 years.

BACKGROUND: Advances have occurred in the management of digestive tract cancers, but it is not known how much they have benefited the elderly. AIMS: To determine trends in treatment, stage at diagnosis and prognosis of digestive tract cancers among patients aged > or =80 years in two well-defined French populations. DESIGN: Time trends were studied in three age classes and in 5 four-year time intervals. A multivariate relative survival analysis was performed to estimate the independent effect of both age and period on prognosis. RESULTS: Five-year relative survival rates were 1.9% for oesophageal cancer, 12% for stomach cancer, 41% for colon cancer and 37% for rectal cancer. The survival rates improved between the first and the fifth period for all cancer sites except for oesophageal cancer. This improvement remained significant after adjustment for age, sex, site and treatment. It was associated with an increase in the proportion of patients who underwent curative resection. Very few patients received adjuvant chemotherapy. The use of adjuvant radiotherapy for rectal and oesophageal cancers did not significantly increase over time. CONCLUSIONS: Except for oesophageal cancers, substantial advances in the care of digestive tract cancers in the elderly have been achieved. Surgery should not be restricted on the basis of age alone. Further improvements can be made in particular to enhance adjuvant therapy whenever possible.

Age Factors↗
PubMed2006

Epidermal growth factor receptor expression and activation in neuroendocrine tumours.

Epidermal growth factor receptor (EGFR) is expressed in many cancers and is associated with poor prognosis. EGFR activation pathways have been well characterised using tumour cell lines and are known to involve EGFR activation through autophosphorylation. Phosphorylation of downstream signalling molecules, such as ERK1/2 (extra-cellular regulated kinase 1 and 2) and PKB/Akt (protein kinase B), leads to enhanced tumour cell survival and proliferation. Although EGFR expression has been determined in neuroendocrine tumour tissue, its activation and subsequent effects on the downstream signalling molecules, ERK1/2 and Akt, have not been studied. We therefore planned to determine the role of EGFR in neuroendocrine tumours (NETs) by determining its pattern of expression and activation, and the subsequent activation of downstream signalling molecules ERK1/2 and Akt. Paraffin-embedded tumour tissue was available from 98 patients with NETs (39 foregut, 42 midgut, four hindgut, five paragangliomas, and four of unknown origin). Immunohistochemical evaluation was performed for the expression of EGFR, p-EGFR, p-Akt, and p-ERK1/2. Ninety-six percent of tumour samples were positive for EGFR expression; 63% were positive for activated EGFR; 76% were positive for activated Akt; and 96% were positive for activated ERK1/2. Importantly, the histological score for the activation of Akt and ERK1/2 correlated with the histological score for activated EGFR. These data provide a rationale for considering EGFR inhibitors in the treatment of NETs. Additionally, direct inhibition of Akt and ERK1/2 may provide further therapeutic options in the treatment of NETs in the future.

3-Phosphoinositide-Dependent Protein Kinases↗
PubMed2005

Reoperative pancreaticoduodenectomy for periampullary carcinoma.

BACKGROUND: Potentially resectable periampullary tumours may not be treated appropriately due to lack of local expertise in both assessment of resectability and resection in referring centres. Tata Memorial Hospital is a major referral centre for oncology and these patients are finally referred to this institution. In carefully selected patients, resection can be accomplished. The purpose of the present paper was to determine the perioperative morbidity and mortality for patients undergoing reoperative pancreaticoduodenectomy at a major comprehensive cancer centre. METHODS: Between January 1991 and December 2001 15 patients, who had undergone previous non-resectional surgery for operable periampullary carcinoma, underwent re-exploration. The perioperative morbidity and mortality were analysed and compared with that of the group of patients undergoing primary pancreaticoduodenectomy (143 patients) in the same period. RESULTS: All the 15 patients undergoing re-exploration had a successful resection by pancreaticoduodenectomy. In the reoperative group eight patients (53%) underwent classic pancreaticoduodenectomy and seven patients (46%) had a pylorus-preserving pancreaticoduodenectomy, as compared to 102 (71%) and 41 (29%) patients in the primary surgery group, respectively. Although the mean operative time and the estimated blood loss were higher in the reoperative group, the morbidity and mortality rates were similar in the two groups. The overall 30-day mortality rate was 6.6% and 6.9% in the reoperative and the primary surgery group, respectively. Major morbidity occurred in two of the 15 patients (13.3%), and one patient (6.6%) died following surgery in the reoperative group. CONCLUSION: Reoperative pancreaticoduodenectomy can be performed safely in carefully selected patients with resectable, localized periampullary tumours with similar morbidity and mortality to patients undergoing primary surgery.

Adenocarcinoma↗
PubMed2002

The risk of subsequent primary cancers after colorectal cancer in southeast England.

BACKGROUND: Multiple cancers may occur in an individual because of a genetic predisposition, environmental exposure, cancer therapy, or immunological deficiency. Colorectal cancer is one of the most commonly diagnosed cancers, and inherited factors play an important role in its aetiology. AIMS: To characterise the occurrence of multiple primary cancers in patients diagnosed with colorectal cancer and explore the possibility of a common aetiology for different cancer sites. PATIENTS: The Thames Cancer Registry database was used to identify patients with a first colorectal cancer, resident in the North or South Thames region, diagnosed between 1 January 1961 and 31 December 1995. A total of 127 281 patients were included, 61 433 men and 65 848 women. METHODS: Observed numbers of cancers occurring after the diagnosis of colorectal cancer were compared with expected numbers, calculated using appropriate age, sex, and period specific rates, to obtain standardised incidence ratios. The occurrence of colorectal cancers subsequent to cancers at other sites was also examined. RESULTS: Small intestinal cancer was significantly increased in men diagnosed with colorectal cancer before the age of 60 years and in women diagnosed with colorectal cancer after the age of 65 years. Colorectal cancer was also significantly increased after a first diagnosis of cancer of the small intestine. Other cancer sites with a significant increase after colorectal cancer included the cervix uteri, corpus uteri, and ovary. CONCLUSIONS: Patients with colorectal cancer are at increased risk of developing cancer at a number of other sites. Some of these associations are consistent with the effects of known inherited cancer susceptibility genes.

Adult↗
PubMed2005

BRAF and NRAS mutations are uncommon in melanomas arising in diverse internal organs.

BACKGROUND: Malignant melanoma arising from different body compartments may be associated with differing aetiological factors and clinical behaviour, and may manifest diverse molecular genetic profiles. Although many studies have focused on cutaneous melanoma, little is known of mucosal and other types of melanoma. In particular, malignant melanoma of soft parts is different from other melanomas in many respects, yet manifests a common melanocytic differentiation. Mutation of BRAF is now known to be common in cutaneous melanomas, and raises possible new therapeutic options of anti-RAF treatment for these patients. Few data are available for non-cutaneous melanomas. AIMS: To study the incidence of BRAF and NRAS mutations in melanomas arising in diverse internal organs. METHODS: Fifty one melanomas from various internal organs were investigated for BRAF and NRAS mutation by direct DNA sequencing. RESULTS: BRAF and NRAS mutations were found in two and five mucosal melanomas arising from the aerodigestive and female genital tracts (n = 36). Their occurrence is mutually exclusive, giving a combined mutation incidence rate of 19.4% in mucosal melanomas. Both BRAF and NRAS mutations were absent in malignant melanoma of soft parts (n = 7). BRAF mutation was also absent in uveal melanoma (n = 6), but was seen in two of five cutaneous melanomas. The incidence of BRAF or combined BRAF/NRAS mutations in all non-cutaneous groups was significantly lower than published rates for cutaneous melanomas. CONCLUSION: Each melanoma subtype may have a unique oncogenetic pathway of tumour development, and only a small fraction of non-cutaneous melanomas may benefit from anti-RAF treatment.

Adolescent↗
PubMed2006

Expression of beta-catenin in gastroenteropancreatic endocrine tumours: a study of 229 cases.

AIMS: To clarify the role of beta-catenin in digestive endocrine carcinogenesis, a large and representative series of gastroenteropancreatic endocrine tumours was analysed in order to determine the incidence and pattern of beta-catenin changes and to analyse the clinical and histological characteristics of the tumours presenting immunohistochemically detectable changes in beta-catenin expression. METHODS: 229 cases of gastroenteropancreatic endocrine tumours (stomach, 11; duodenum and ampulla, 29; jejunum and ileum, 51; appendix, 13; colon and rectum, 17; and pancreas, 108) were studied by immunohistochemistry to assess the pattern of distribution of beta-catenin (membranous, cytoplasmic or nuclear). DNA was analysed to detect mutations in exon 3 of the CTNNB1 gene. RESULTS: The distribution of immunoreactive beta-catenin protein was membranous in 164 cases, cytoplasmic in 58 cases and nuclear in seven cases. No mutation was detected in exon 3 of the CTNNB1 gene in any case. The seven cases with nuclear accumulation of beta-catenin were large tumours (mean size 44 (standard deviation (SD) 18.5) mm) with metastases, including liver metastases in five cases, high Ki-67 index (mean 34% (SD 16.5%)) and cyclin D1 overexpression; p53 accumulation was detected in six cases. Five patients died of disease; the mean (SD) survival was 13.6 (4.8) months. CONCLUSIONS: Immunohistochemically detectable nuclear accumulation of beta-catenin is infrequent in gastroenteropancreatic endocrine tumours and is usually not associated with mutations in CNNTB1 exon 3. Changes in beta-catenin expression are late events in digestive endocrine carcinogenesis, associated with tumour progression and dissemination.

Adult↗