Colon cancer in Luxembourg: a national population-based data report, 1988–1998

BACKGROUND: Over the last two decades time trends in incidence rates of colorectal cancer, changes in the proportions of stage at diagnosis and changes in the anatomic sub-site distribution of colon cancers have been reported in some European countries. In order to determine a strategy for early detection of colon cancer in the Grand-Duchy of Luxembourg, all consecutive colon adenocarcinomas diagnosed during the period 1988–1998 at a nation-wide level were reviewed. METHODS: The population-based data of the national Morphologic Tumour Registry report all new high-grade adenomas (i.e. high-grade intraepithelial adenomatous neoplasias) and all consecutive new invasive adenocarcinomas of the colon diagnosed in the central department of pathology. Attention has been focused on variations in incidence, stage, anatomical site distribution and survival rates. Rectal cancers were excluded. RESULTS: Over the study period, 254 new colonic high-grade adenomas and 1379 new invasive adenocarcinomas were found; the crude incidence rates of colon adenocarcinomas grew steadily by 30%. Comparing the two 5-year periods 1988–1992 and 1994–1998, the crude incidence rates of high-grade adenomas (stage 0) rose by 190%, that of stage I cases by 14.3%, stage II cases 12.9% and stage III cases 38.5%, whereas the crude incidence rates of stage IV cases decreased by 11.8%. The high-grade adenoma/adenocarcinoma ratio increased. The right-sided colonic adenocarcinomas in elderly patients (>69 years) increased by 76%. The observed survival rates correlated with tumour stages. The overall observed 5-year survival rate (stage I-IV) was 51 ± 3% (95% confidence interval). CONCLUSION: The increasing incidence rates of colon adenocarcinomas, the persistence of advanced tumour stages (stage III), the mortality rates which remain stable, and the changing trends in the age- and sub-site distribution underline the need for preventive measures at the age of 50 in asymptomatic patients to reduce mortality from colo(rectal) cancer

Surgical outcomes for colon and rectal cancer over a decade: results from a consecutive monocentric experience in 902 unselected patients

<p>Abstract</p> <p>Background</p> <p>This study evaluates the surgical morbidity and long-term outcome of colorectal cancer surgery in an unselected group of patients treated over the period 1994–2003.</p> <p>Methods</p> <p>A consecutive series of 902 primary colorectal cancer patients (489 M, 413 F; mean age: 63 years ± 11 years, range: 24–88 years) was evaluated and prospectively followed in a university hospital (mean follow-up 36 ± 24 months; range: 3–108 months). Perioperative mortality, morbidity, overall survival, curative resection rates, recurrence rates were analysed.</p> <p>Results</p> <p>Of the total, 476 colorectal cancers were localized to the colon (CC, 53%), 406 to the rectum (RC, 45%), 12 (1%) were multicentric, and 8 were identified as part of HNPCC (1%). Combining all tumours, there were 186 cancers (20.6%) defined as UICC stage I, 235 (26.1%) stage II, 270 (29.9%) stage III and 187 (20.6%) stage IV cases. Twenty-four (2.7%) cases were of undetermined stage. Postoperative complications occurred in 38% of the total group (37.8% of CC cases, 37.2% of the RC group, 66.7% of the synchronous cancer patients and 50% of those with HNPCC, p = 0.19) Mortality rate was 0.8%, (1.3% for colon cancer, 0% for rectal cancer; p = 0.023). Multivisceral resection was performed in 14.3% of cases. Disease-free survival in cases resected for cure was 73% at 5-years and 72% at 8 years. The 5- and 8-year overall survival rates were 71% and 61% respectively (total cases). At 5-year analysis, overall survival rates are 97% for stage I disease, 87% for stage II, 73% for stage III and 22% for stage IV respectively (p < 0.0001). The 5-year overall survival rates showed a marked difference in R0, R1+R2 and non resected patients (82%, 35% and 0% respectively, p < 0.0001). On multivariate analysis, resection for cure and stage at presentation but not tumour site (colon vs. rectum) were independent variables for overall survival (p < 0.0001).</p> <p>Conclusion</p> <p>A prospective, uniform follow-up policy used in a single institution over the last decade provides evidence of quality assurance in colorectal cancer surgery with high rates of resection for cure where only stage at presentation functions as an independent variable for cancer-related outcome.</p

Detection of occult carcinomatous diffusion in lymph nodes from head and neck squamous cell carcinoma using real-time RT–PCR detection of cytokeratin 19 mRNA

The aim of the present study was to evaluate the occult lymph node carcinomatous diffusion in head and neck squamous cell carcinoma (HNSCC). A total of 1328 lymph nodes from 31 patients treated between 2004 and 2005 were prospectively evaluated by routine haematoxylin–eosin–safran (HES) staining, immunohistochemistry (IHC) and real-time Taqman reverse–transcriptase polymerase chain reaction (real-time RT–PCR) assay. Amplification of cytokeratin 19 (CK19) mRNA transcripts using real-time RT–PCR was used to quantify cervical micrometastatic burden. The cervical lymph node metastatic rates determined by routine HES staining and real-time RT–PCR assay were 16.3 and 36.0%, respectively (P<0.0001). A potential change in the nodal status was observed in 13 (42.0%) of the 31 patients and an atypical pattern of lymphatic spread was identified in four patients (12.9%). Moreover, CK19 mRNA expression values in histologically positive lymph nodes were significantly higher than those observed in histologically negative lymph nodes (P<0.0001). These results indicate that real-time RT–PCR assay for the detection of CK19 mRNA is a sensitive and reliable method for the detection of carcinomatous cells in lymph nodes. This type of method could be used to reassess lymph node status according to occult lymphatic spread in patients with HNSCC

Is standard breast-conserving therapy (BCT) in elderly breast cancer patients justified? A prospective measurement of acute toxicity according CTC-classification

<p>Abstract</p> <p>Background</p> <p>Breast conserving therapy (BCT) is an accepted treatment for early-stage breast cancer. This study aimed to measure prospectively acute radiation-related toxicity and to create a comprehensive data base for long-term temporal analyses of 3D conformal adjuvant radiotherapy. The specific aspect of age has been neglected by traditional research. Therefore, the impact of age on acute BCT toxicity should be also specifically adressed.</p> <p>Methods</p> <p>Toxicity was measured in 109 patients at initiation (t1), during radiotherapy (t2-t7), and 6 weeks after treatment completion (t8) using a new topographic module. Organ systems were recorded in 15 scales and scored according to symptom intensity (grade 0-5) based on CTC (Common Toxicity Criteria) -classification. Radiotherapy was virtually CT-based planned and applied with 6-MeV-photons. Mean total dose was 60.1 Gy. Patients were stratified by age in 3 Groups: <50, 50-60, and >60 years.</p> <p>Results</p> <p>Registered toxicity was generally low. Mean overall-grade climbed from 0.29-0.40 (t1-t7), and dropped to 0.23 (t8). Univariate analyses revealed slightly higher toxicity in older (> 60 years) versus young patients (< 50 years) in 2 scales only: breast-symmetry (p = 0.033), and arm function (p = 0.007). However, in the scale "appetite" toxicity was higher in younger (< 50 years) versus older (> 60 years) patients (p = 0.039). Toxicity differences in all other scales were not significant. Between older (> 60 years) and midaged patients (50-60 years) no significant differences in toxicity were found. This was also true for the comparison between young (< 50 years) versus midaged patient groups (50-60 years).</p> <p>Conclusion</p> <p>The treatment concept of BCT for breast cancer is generally well tolerated. The toxicity-measurement with the new topographic module is feasible. Not modified standard treatment for BC should be performed in elderly women.</p

Microsatellite instability in thyroid tumours and tumour-like lesions

Fifty-one thyroid tumours and tumour-like lesions were analysed for instability at ten dinucleotide microsatellite loci and at two coding mononucleotide repeats within the transforming growth factor β (TGF-β) type II receptor (TβRII) and insulin-like growth factor II (IGF-II) receptor (IGFIIR) genes respectively. Microsatellite instability (MI) was detected in 11 out of 51 cases (21.5%), including six (11.7%) with MI at one or two loci and five (9.8%) with Ml at three or more loci (RER+ phenotype). No mutations in the TβRII and IGFIIR repeats were observed. The overall frequency of MI did not significantly vary in relation to age, gender, benign versus malignant status and tumour size. However, widespread MI was significantly more frequent in follicular adenomas and carcinomas than in papillary and Hürthle cell tumours: three out of nine tumours of follicular type (33.3%) resulted in replication error positive (RER+), versus 1 out of 29 papillary carcinomas (3.4%, P = 0.01), and zero out of eight Hürthle cell neoplasms. Regional lymph node metastases were present in five MI-negative primary cancers and resulted in MI-positive in two cases. © 1999 Cancer Research Campaig

Prevalence of von Hippel-Lindau gene mutations in sporadic renal cell carcinoma: results from the Netherlands cohort study

BACKGROUND: Biallelic von Hippel-Lindau (VHL) gene defects, a rate-limiting event in the carcinogenesis, occur in approximately 75% of sporadic clear-cell Renal Cell Carcinoma (RCC). We studied the VHL mutation status in a large population-based case group. METHODS: Cases were identified within the Netherlands cohort study on diet and cancer, which includes 120,852 men and women. After 11.3 years of follow-up, 337 incident cases with histologically confirmed epithelial cancers were identified. DNA was isolated from paraffin material collected from 51 pathology laboratories and revised by one pathologist, leaving material from 235 cases. VHL mutational status was assessed by SSCP followed by direct sequencing, after testing SSCP as a screening tool in a subsample. RESULTS: The number of mutations was significantly higher for clear-cell RCC compared to other histological types. We observed 131 mutations in 114 out of 187 patients (61%) with clear-cell RCC. The majority of mutations were truncating mutations (47%). The mean tumor size was 72.7 mm for mutated tumors compared to 65.3 mm for wildtype tumors (p = 0.06). No statistically significant differences were observed for nuclear grade, TNM distribution or stage. In other histological types, we observed 8 mutations in 7 out of 48 patients (15%), 1 mutation in 1 of 6 oncocytoma, 3 mutations in 2 of 7 chromophobe RCC, 2 mutations in 2 of 30 papillary RCC, no mutations in 1 collecting duct carcinoma and 2 mutations in 2 of 4 unclassified RCC. CONCLUSION: VHL mutations were detected in 61% of sporadic clear-cell RCC. VHL mutated and wildtype clear-cell RCC did not differ with respect to most parameters

Prognostic value of Goseki histological classification in adenocarcinoma of the cardia

Various histologic classification systems have been proposed as prognostic factors for gastric cancer. We assessed the prognostic value of Goseki classification as well as the TNM staging system, histological tumour grading, Lauren, WHO, Goseki and Siewert classifications in 100 patients with cardia carcinoma undergoing curative surgery. Two patients were lost at follow-up. The median time of follow-up in the remaining patients was 32.9 months after surgery (range: 0.1–142.1 months). No differences in survival rates were observed according to tumour grading, Lauren or WHO histologic or Siewert topographical classification. No differences were found according to Goseki classes, when considering either the mucin content of the carcinoma (types I and III vs II and IV) or the differentiation grade (types I and II vs III and IV). Multivariate analysis showed that the only lymph node positivity was a significant predictor of survival: 7.2% of patients with, but 41.5% of those without nodal involvement were alive after five years (P=0.0001). In conclusion, we found no prognostic role for Goseki or the traditional histological indexes, while the TNM staging system and particularly lymph node positivity were the main predictors of survival in patients with cardia adenocarcinoma

Detection of sentinel and non-sentinel lymph node micrometastases by complete serial sectioning and immunohistochemical analysis for gastric cancer

<p>Abstract</p> <p>Background</p> <p>We investigated the presence and distribution of the sentinel and the non-sentinel node micrometastases using complete serial sectioning and immunohistochemical staining (IHC), to inspect whether lymph node micrometastases spread to the sentinel lymph nodes first.</p> <p>Methods</p> <p>A total of 35 patients, who underwent gastrectomy with a sentinel lymph node biopsy for gastric cancer, were enrolled in this study. Total of 1028 lymph nodes of 35 patients having gastric cancer without metastasis of lymph node by permanent section with hematoxylin and eosin staining (H&E) were selected. There were 252 sentinel nodes and the other 776 were non-sentinel nodes. All nodes were sectioned serially and stained alternately with H&E and IHC. Lymph node micrometastases was defined as proving to be positive first either the IHC or the complete serial sectioning.</p> <p>Results</p> <p>Micrometastases were detected in 4 (11%) of the 35 patients, 6 (0.58%) of 1028 nodes. Of these 4 patients, 3 had micrometastases exclusively in sentinel nodes, and the other had micrometastasis in both sentinel and non-sentinel nodes. There was no patient who had the micrometasitases only in non-sentinel nodes.</p> <p>Conclusion</p> <p>These results support the concept that lymph node micrometastasis of gastric cancer spreads first to sentinel nodes.</p

Microsatellite instability and intratumoural heterogeneity in 100 right-sided sporadic colon carcinomas

Microsatellite instability has been proposed as an alternative pathway of colorectal carcinogenesis. The aim of this study was to evaluate the interest of immunohistochemistry as a new tool for highlighting mismatch repair deficiency and to compare the results with a PCR-based microsatellite assay. A total of 100 sporadic proximal colon adenocarcinomas were analysed. The expression of hMLH1, hMSH2 and hMSH6 proteins evaluated by immunohistochemistry was altered in 39% of the cancers, whereas microsatellite instability assessed by PCR was detected in 43%. There was discordance between the two methods in eight cases. After further analyses performed on other tumoural areas for these eight cases, total concordance between the two techniques was observed (Kappa=100%). Our results demonstrate that immunohistochemistry may be as efficient as microsatellite amplification in the detection of unstable phenotype provided that at least two samples of each carcinoma are screened, because of intratumoural heterogeneity