Younger age as a bad prognostic factor in patients with carcinoma of the cervix.

OBJECTIVE: To verify the influence of age on the prognosis of cervix carcinoma. STUDY DESIGN: Five hundred and sixty eight patients treated for a FIGO stage IB-IVA with radical irradiation in the Centre Hospitalier Universitaire Vaudois of Lausanne were subdivided according to the following age categories: < or = 45, 46-60, 61-69 and >70 years. Taking the 46-60 years age group as the reference, the hazard ratios (HR) of death and corresponding 95% confidence intervals (95% CI) were estimated by means of a Cox multivariate analysis. RESULTS: The 5-year survival rates were, respectively, 57%, 67%, 60% and 45%. For the youngest women the risk of death was significantly increased (HR = 2.00, 95% CI [1.32-3.00]) and was even more accentuated in advanced stages. CONCLUSION: Age under 45 years is a bad prognostic factor in carcinoma of the cervix.

Clinical follow-up of women infected with human papillomavirus-16, either alone or with other human papillomavirus types: identification of different risk groups.

OBJECTIVES: Evaluation of the clinical impact of multiple infections of the cervix by human papillomavirus, including human papillomavirus-16, compared with single human papillomavirus-16 infection. STUDY DESIGN: One hundred sixty-nine women were classified in 3 categories depending on their human papillomavirus profile: human papillomavirus-16 only, human papillomavirus-16 and low-risk type(s), and human papillomavirus-16 and other high-risk type(s). Cervical brush samples were analyzed for human papillomavirus DNA by polymerase chain reaction and reverse line blot hybridization. All women were evaluated with colposcopy during 24 months or more. Management was according to the Bethesda recommendations. RESULTS: Women infected with human papillomavirus-16 and other high-risk human papillomavirus type(s) presented more progression or no change in the grade of dysplasia, compared with women of the other groups (relative risk [RR], 1.39; 95% confidence interval [CI], 1.07-1.82; P = .02 at 6 months; RR, 2.10; 95% CI, 1.46-3.02; P < .001 at 12 months; RR, 1.82; 95% CI, 1.21-2.72; P = .004 at 24 months). CONCLUSION: Coinfection of women with human papillomavirus-16 and other high-risk human papillomavirus type(s) increases the risk of unfavorable evolution.

Age-specific incidence of all neoplasms after colorectal cancer.

PURPOSE: Patients diagnosed with a specific neoplasm tend to have a subsequent excess risk of the same neoplasm. The age incidence of a second neoplasm at the same site is approximately constant with age, and consequently the relative risk is greater at younger age. It is unclear whether such a line of reasoning can be extended from a specific neoplasm to the incidence of all neoplasms in subjects diagnosed with a defined neoplasm. METHODS: We considered the age-specific incidence of all non-hormone-related epithelial neoplasms after a first primary colorectal cancer (n = 9542) in the Vaud Cancer Registry data set. RESULTS: In subjects with a previous colorectal cancer, the incidence rate of all other epithelial non-hormone-related cancers was stable around 800 per 100,000 between age 30 and 60 years, and rose only about twofold to reach 1685 at age 70 to 79 years and 1826 per 100,000 at age 80 years or older. After excluding synchronous cancers, the rise was only about 1.5-fold, that is, from about 700 to 1000. In the general population, the incidence rate of all epithelial non-hormone-related cancers was 29 per 100,000 at age 30 to 39 years, and rose 30-fold to 883 per 100,000 at age 70 to 79 years. Excluding colorectal cancers, the rise of all non-hormone-related cancers was from 360 per 100,000 at age 40 to 49 years to 940 at age 70 to 79 years after colorectal cancer, and from 90 to 636 per 100,000 in the general population (i.e., 2.6- vs. 7.1-fold). CONCLUSIONS: The rise of incidence with age of all epithelial non-hormone-related second cancers after colorectal cancer is much smaller than in the general population. This can possibly be related to the occurrence of a single mutational event in a population of susceptible individuals, although alternative models are plausible within the complexity of the process of carcinogenesis.

Sawhorse-type diruthenium tetracarbonyl complexes containing porphyrin-derived ligands as highly selective photosensitizers for female reproductive cancer cells.

Diruthenium tetracarbonyl complexes of the type [Ru2(CO)4(l2-g2-O2CR)2L2] containing a Ru-Ru backbone with four equatorial carbonyl ligands, two carboxylato bridges, and two axial two-electron ligands in a sawhorse-like geometry have been synthesized with porphyrin-derived substituents in the axial ligands [1: R is CH3, L is 5-(4-pyridyl)-10,15,20-triphenyl-21,23H-porphyrin], in the bridging carboxylato ligands [2: RCO2H is 5-(4-carboxyphenyl)-10,15,20-triphenyl-21,23H-porphyrin, L is PPh3; 3: RCO2H is 5-(4-carboxyphenyl)-10,15,20-triphenyl-21,23H-porphyrin, L is 1,3,5-triaza-7-phosphatricyclo [3.3.1.1]decane], or in both positions [4: RCO2H is 5-(4-carboxyphenyl)-10,15,20-triphenyl-21,23H-porphyrin, L is 5-(4-pyridyl)-10,15,20-triphenyl-21,23H-porphyrin]. Compounds 1-3 were assessed on different types of human cancer cells and normal cells. Their uptake by cells was quantified by fluorescence and checked by fluorescence microscopy. These compounds were taken up by human HeLa cervix and A2780 and Ovcar ovarian carcinoma cells but not by normal cells and other cancer cell lines (A549 pulmonary, Me300 melanoma, PC3 and LnCap prostate, KB head and neck, MDAMB231 and MCF7 breast, or HT29 colon cancer cells). The compounds demonstrated no cytotoxicity in the absence of laser irradiation but exhibited good phototoxicities in HeLa and A2780 cells when exposed to laser light at 652 nm, displaying an LD50 between 1.5 and 6.5 J/cm2 in these two cell lines and more than 15 J/cm2 for the others. Thus, these types of porphyric compound present specificity for cancer cell lines of the female reproductive system and not for normal cells; thus being promising new organometallic photosensitizers.

Trends in cancer mortality in Brazil, 1980-2004.

Scanty information, limited to selected areas of the country, is available on cancer mortality in Brazil. Age-standardized (world population) mortality rates between 1980 and 2004, derived from the WHO database, were computed for all cancers and 24 major cancer sites in Brazil. Joinpoint regression analyses were used to identify the significant changes in trends and estimate annual percent change (APC) in rates. Total cancer mortality rates increased over the last decade in men (APC = 0.5) to reach 101.2/100 000, and in women (APC = 0.3) to reach 71.3/100 000. In men, upward trends were observed for cancers of the oral cavity and pharynx with a rate of 5.9/100 000 in 2000-2004, intestines (whose rate, however was low, i.e. 7.6), prostate (12.2), and leukemias (3.4). Male lung cancer increased until 1993 (APC = 1.39) and decreased thereafter (APC = -0.29), with a relatively low rate of 16.2/100 000 in 2000-2004. In women, there were steady upward trends for cancers of the lung (APC = 2.3), reaching 6.2/100 000 in 2000-2004, and leukemias (2.5). Breast cancer mortality leveled off at around 10/100 000 in the last decade, whereas declines were observed for cancers of the uterus, whose rate (8.3) however, remained comparatively high. Declines were observed for stomach cancer in both sexes, with rates of 11.1 in men and 4.6 in women. In conclusion, the key issues of cancer mortality in Brazil are the high rates of head and neck cancers in men and (cervix) uterine cancer in women, that is, in principle cancers that are largely avoidable through prevention, screening, and early diagnosis.

Colposcopic evaluation after a repeat atypical squamous cells of undetermined significance (ASCUS) smear.

OBJECTIVES: Management of patients with atypical squamous cells of undetermined significance (ASCUS) remains controversial. We chose to repeat the Pap smear after four months. If ASCUS persisted in this second test, the patient was advised to undergo colposcopy. Our objective is to determine the clinical significance and the prediction of neoplasia among these patients through a colposcopic examination. METHODS: Of 29,827 patients who had a Pap smear, ASCUS were detected in 1387 (5%) and persisted in the repeat smear of 225 (16%). Colposcopy and an additional Pap smear were performed on 186 patients. RESULTS: Out of 186 colposcopic evaluations, 91 (49%) were normal and the patients had a negative Pap smear. Colposcopy was abnormal in 95/186 patients (51%) (Table 1). Histology of the directed biopsies revealed 38 (21%) low-grade squamous intraepithelial lesions (LSIL) and 17 (9%) high-grade squamous intraepithelial lesions (HSIL). Forty patients (21%) with normal biopsies had ASCUS for the third time in the Pap smear. CONCLUSIONS: Colposcopic evaluation after a repeated Pap smear with ASCUS is an appropriate cost-effective management. Finding 30% of LSIL or HSIL justifies this additional investigation.

Diagnosis and workup of 522 consecutive patients with neuroendocrine neoplasms in Switzerland.

BACKGROUND: Neuroendocrine neoplasms (NENs) are difficult to diagnose. We used SwissNET data to characterise NEN patients followed in the two academic centres of western Switzerland (WS), and to compare them with patients followed in eastern Switzerland (ES) as well as with international guidelines. METHOD: SwissNET is a prospective database covering data from 522 consecutive patients (285 men, 237 women) from WS (n = 99) and ES (n = 423). RESULTS: Mean ± SD age at diagnosis was 59.0 ± 15.7 years. Overall, 76/522 experienced a functional syndrome, with a median interval of 1.0 (IQR: 1.0-3.0) year between symptoms onset and diagnosis. A total of 51/522 of these tumours were incidental. The primary tumour site was the small intestine (29%), pancreas (21%), appendix (18%) and lung (11%) in both regions combined. In all, 513 functional imaging studies were obtained (139 in WS, 374 in ES). Of these, 381 were 111In-pentetreotide scintigraphies and 20 were 68Ga-DOTATOC PET. First line therapy was surgery in 87% of patients, medical therapy (biotherapy or chemotherapy) in 9% and irradiation in 3% for both regions together. CONCLUSION: Swiss NEN patients appear similar to what has been described in the literature. Imaging by somatostatin receptor scintigraphy (SRS) is widely used in both regions of Switzerland. In good accordance with published guidelines, data on first line therapy demonstrate the crucial role of surgery. The low incidence of biotherapy suggests that long-acting somatostatin analogues are not yet widely used for their anti-proliferative effects. The SwissNET initiative should help improve compliance with ENETS guidelines in the workup and care of NEN patients.

Cancer risk in the Swiss HIV Cohort Study: associations with immunodeficiency, smoking, and highly active antiretroviral therapy.

BACKGROUND: Persons infected with human immunodeficiency virus (HIV) have an increased risk for several cancers, but the influences of behavioral risk factors, such as smoking and intravenous drug use, and highly active antiretroviral therapy (HAART) on cancer risk are not clear. METHODS: Patient records were linked between the Swiss HIV Cohort Study and Swiss cantonal cancer registries. Observed and expected numbers of incident cancers were assessed in 7304 persons infected with HIV followed for 28,836 person-years. Relative risks for cancer compared with those for the general population were determined by estimating cancer registry-, sex-, age-, and period-standardized incidence ratios (SIRs). RESULTS: Highly elevated SIRs were confirmed in persons infected with HIV for Kaposi sarcoma (KS) (SIR = 192, 95% confidence interval [CI] = 170 to 217) and non-Hodgkin lymphoma (SIR = 76.4, 95% CI = 66.5 to 87.4). Statistically significantly elevated SIRs were also observed for anal cancer (SIR = 33.4, 95% CI = 10.5 to 78.6); Hodgkin lymphoma (SIR = 17.3, 95% CI = 10.2 to 27.4); cancers of the cervix (SIR = 8.0, 95% CI = 2.9 to 17.4); liver (SIR = 7.0, 95% CI = 2.2 to 16.5); lip, mouth, and pharynx (SIR = 4.1, 95% CI = 2.1 to 7.4); trachea, lung, and bronchus (SIR = 3.2, 95% CI = 1.7 to 5.4); and skin, nonmelanomatous (SIR = 3.2, 95% CI = 2.2 to 4.5). In HAART users, SIRs for KS (SIR = 25.3, 95% CI = 10.8 to 50.1) and non-Hodgkin lymphoma (SIR = 24.2, 95% CI = 15.0 to 37.1) were lower than those for nonusers (KS SIR = 239, 95% CI = 211 to 270; non-Hodgkin lymphoma SIR = 99.3, 95% CI = 85.8 to 114). Among HAART users, however, the SIR (although not absolute numbers) for Hodgkin lymphoma (SIR = 36.2, 95% CI = 16.4 to 68.9) was comparable to that for KS and non-Hodgkin lymphoma. No clear impact of HAART on SIRs emerged for cervical cancer or non-acquired immunodeficiency syndrome-defining cancers. Cancers of the lung, lip, mouth, or pharynx were not observed among nonsmokers. CONCLUSION: In persons infected with HIV, HAART use may prevent most excess risk of KS and non-Hodgkin lymphoma, but not that of Hodgkin lymphoma and other non-acquired immunodeficiency syndrome-defining cancers. No cancers of the lip, mouth, pharynx, or lung were observed in nonsmokers.

Ganglion sentinelle dans les cancers du col de faible stade. Données actuelles. Assurance qualité. Perspectives [Sentinel lymph node in low stage cervical cancers. Current data. Quality assurance. Prospects].

Le prélèvement des ganglions sentinelles apparaît comme une technique séduisante pour l'évaluation ganglionnaire des cancers du col utérin de faible stade. La sélection d'une population à bas risque de métastase ganglionnaire, un entraînement minimal et le respect de quelques règles simples permettent de limiter le risque de faux négatif au minimum. La technique apporte des informations supplémentaires sur le plan anatomique en identifiant des ganglions situés en dehors des zones habituelles de curage, et sur le plan histologique avec la mise en évidence de cellules tumorales isolées et surtout de micrométastases dont la valeur pronostique est suspectée Sentinel node biopsy appears as a promising technique for the assessment of nodal disease in early cervical cancers. Selection of a population with a low risk of nodal metastasis, a minimal training, and simple rules allow a low false negative rate. Sentinel node biopsy provides supplementary information, such as anatomical information (nodes outside of routine lymphadenectomy areas) and histological information (isolated tumors cells and micrometastases).

Radiation therapy duration influences overall survival in patients with cervical carcinoma.

OBJECTIVE: This article analyses the influence of treatment duration on survival in patients with invasive carcinoma of the cervix treated by radical radiation therapy. METHOD: Three hundred and sixty patients with FIGO stage IB-IIIB carcinoma of the cervix were treated in Lausanne (Switzerland) with external radiation and brachytherapy as first line therapy. Median therapy duration was 45 days. Patients were classified according to the duration of the therapies, taking 60 days (the 75th percentile) as an arbitrary cut-off. RESULTS: The 5-year survival was 61% (S.E. = 3%) for the therapy duration group of less than 60 days and 53% (S.E. = 7%) for the group of more than 60 days. In terms of univariate hazard ratio (HR), the relative difference between the two groups corresponds to a 50% increase of deaths (HR = 1.53, 95% CI = 1.03-2.28) for the longer therapy duration group (P = 0.044). In a multivariate analysis, the magnitude of estimated relative hazards for the longer therapies are confirmed though significance was reduced (HR = 1.52, 95% CI = 0.94-2.45, P = 0.084). CONCLUSION: These findings suggest that short treatment duration is a factor associated with longer survival in carcinoma of the cervix.

Effects of age, birth cohort and period of death on Swiss cancer mortality, 1951-1984.

Swiss death certification data over the period 1951-1984 for total cancer mortality and 30 major cancer sites in the population aged 25 to 74 years were analysed using a log-linear Poisson model with arbitrary constraints on the parameters to isolate the effects of birth cohort, calendar period of death and age. The overall pattern of total cancer mortality in males was stable for period values and showed some moderate decreases in cohort values restricted to the generations born after 1930. Cancer mortality trends were more favourable in females, with steady, though moderate, declines in both cohort and period values. According to the estimates from the model, the worst affected generation for male lung cancer was that born around 1910, and a flattening of trends or some moderate decline was observed for more recent cohorts, although this decline was considerably more limited than in other European countries. There were decreases in cohort and period values for stomach, intestine and oesophageal cancer in both sexes and (cervix) uteri in females. Increases were observed in both cohort and period trends for pancreas and liver in males and for several other neoplasms, including prostate, brain, leukaemias and lymphomas, restricted, however, for the latter sites, to the earlier cohorts and hence partly attributable to improved diagnosis and certification in the elderly. Although age values for lung cancer in females were around 10-times lower than in males, upward trends in female lung cancer cohort values were observed in subsequent cohorts and for period values from the late 1960's onwards. Therefore, future trends in female lung cancer mortality should continue to be monitored. The application of these age/period/cohort models thus provides a summary guide for the reading and interpretation of cancer mortality trends, although it cannot replace careful inspection of single age-specific rates.