Tumour Stage (tumour + stage)

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Distribution within Medical Sciences

Selected Abstracts

Routine testing for mismatch repair deficiency in sporadic colorectal cancer is justified

Robyn Lynne Ward
Abstract This study prospectively examines the accuracy of immunohistochemical staining in the identification of mismatch repair defective (MMRD) colorectal cancer in routine clinical practice. The potential impact of this information on decisions regarding adjuvant treatment and germline testing were quantified. A consecutive series of fresh tissue (836 cancers) was obtained from 786 individuals undergoing curative surgery for colorectal cancer at one institution. As part of normal practice, each tumour was screened for the expression of MLH1 and MSH2 by immunohistochemical staining (IHC) and relevant clinicopathological details were documented. Microsatellite instability (MSI) was assessed using standard markers. Overall, 108 (13%) tumours showed loss of staining for either MLH1 (92 tumours) or MSH2 (16 tumours). The positive predictive value of mismatch repair IHC when used alone in the detection of MSI tumours was 88%, and the negative predictive value was 97%. Specificity and positive predictive value were improved by correlation with microsatellite status. Tumour stage (HR 3.5, 95% CI 2.0,6.0), vascular space invasion (HR 1.9, 95% CI 1.2,3.0) and mismatch repair deficiency (HR 0.2, 95% CI 0.05,0.87) were independent prognostic factors in stages II and III disease. Screening by mismatch repair IHC could reasonably have been expected to prevent ineffective treatment in 3.6% of stage II and 7.6% of stage III patients. The frequency of germline mismatch repair mutations was 0.8%, representing six unsuspected hereditary non-polyposis colorectal cancer (HNPCC) cases. Routine screening of colorectal cancers by mismatch repair IHC identifies individuals at low risk of relapse, and can prevent unnecessary adjuvant treatments in a significant number of individuals. Abnormal immunohistochemistry should be confirmed by microsatellite testing to ensure that false-positive results do not adversely impact on treatment decisions. Copyright © 2005 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [source]

Elective endoscopic management of transitional cell carcinoma first diagnosed in the upper urinary tract

R. Houston Thompson
OBJECTIVE To report our experience using ureteroscopic or percutaneous management of upper urinary tract (UUT) transitional cell carcinoma (TCC) in patients with no history of bladder TCC. PATIENTS AND METHODS Between 1983 and 2004 we identified 22 patients who underwent endoscopic management of TCC first diagnosed in the UUT and in the setting of a normal contralateral kidney. We performed a retrospective chart review and conducted outcome analyses. RESULTS The median (range) age at diagnosis was 64 (37,86) years and the median tumour size was 0.8 (0.3,2.6) cm. The tumour grade was 1, 2, or diagnosed as visual low grade in two (9%), seven (32%), and 13 (59%) patients, respectively; no patient had grade 3 TCC at diagnosis. Tumour stage was Ta or visual Ta in all patients. The median follow-up was 4.9 (0.4,17) years during which 11 (50%) patients developed 21 UUT recurrences and 10 (45%) patients developed bladder TCC. At last follow-up, seven (32%) patients required a nephroureterectomy for recurrent TCC and two (9%) patients died from TCC. Among 13 patients with a diagnosis based on visual inspection only, three recurred with grade 3 invasive TCC during follow-up. No patient with pathological confirmation of low-grade/stage TCC recurred with high-grade or invasive TCC. CONCLUSIONS Recurrence is common after endoscopic management of UUT-TCC, underscoring the need for strict surveillance. Patients diagnosed visually, without adequate tissue for pathological examination, can recur with high-grade invasive TCC. No patient with pathological confirmation of low-grade TCC developed progressive disease during follow-up. [source]

Superficial bladder tumours: analysis of prognostic factors and construction of a predictive index

B. Ali-El-Dein
OBJECTIVES To assess the prognostic factors that could be used to predict tumour recurrence and progression, and to construct and validate a predictive index. PATIENTS AND METHODS Between June 1991 and December 2000, 533 patients (418 men and 115 women; mean age 55.4 years) underwent complete transurethral resection of histologically confirmed pTa and pT1 transitional cell carcinoma of the bladder, after which 377 (test series) were randomized into two subsequent studies, of six groups, to receive adjuvant intravesical sequential bacillus Calmette-Guérin (BCG) and epirubicin, BCG alone, epirubicin (50 or 80 mg), adriamycin 50 mg or no adjuvant therapy. Factors potentially affecting tumour recurrence or progression were assessed using univariate and multivariate analysis, i.e. tumour stage, histological grade, DNA ploidy, history of recurrence, multiplicity, size, tumour configuration, associated carcinoma in situ, recurrence at the first 3-month check cystoscopy and the use of adjuvant therapy. The regression coefficients determined by Cox regression analysis were used to construct a predictive index (PI). The algebraic sum of the regression coefficients of the factors with independent and significant association with disease-free survival for each case represented a proportional hazard score (PHS). The PI was validated in another series of 156 patients (validation series) in whom the same regression coefficients for the same significant factors as the test series were used to categorize it into three risk groups. Kaplan-Meier survival curves were plotted to compare the different risk categories in both test and validation series. RESULTS The mean (sd, range) follow-up in the test and validation series were 58 (19, 5,96) and 28.3 (14.9, 2,94) months, respectively. In the test series, tumour stage, DNA ploidy, multiplicity, history of recurrence, tumour configuration, cystoscopy result and the type of adjuvant therapy had independent significance for recurrence on multivariate analysis. For progression, the cystoscopy result, DNA ploidy and grade were the only independent and significant predictors. The ranges of PHS for the factors affecting recurrence-free and progression-free survival were 0.0,7.14 and 0.0,5.84, respectively, which were divided equally into three risk categories with significant differences on Kaplan-Meier curves and a log-rank test (P < 0.001). The three categories in the validation series were significantly different from each other and each was comparable with that in the test series. CONCLUSIONS Tumour stage, DNA ploidy, multiplicity, history of recurrence, tumour configuration and type of adjuvant therapy affected independently the rate of recurrence after resecting superficial bladder tumour. Recurrence at the 3-month cystoscopy, histological grade and DNA ploidy were the only predictors of progression to muscle-invasion. The PI dividing the patients into three risk groups with different treatment and follow-up strategies for recurrence and progression was reproducible in a validation series. [source]

Expression of VCAM-1, ICAM-1, E- and P-selectin and tumour-associated macrophages in renal cell carcinoma

B Hemmerlein
Aims Neoangiogenesis is accompanied by an increase in endothelial surface, which can support infiltration by immune cells depending on adhesion molecule expression. Therefore, the expression of cell adhesion molecules on microvessels and epithelial cells was analysed in renal cell carcinomas as compared to tumour-free tissue. Methods and results PECAM-1, CD34, ICAM-1, VCAM-1, VLA-4, P- and E-selectin, the macrophage antigens Ki-M1P and Mac-1, and lymphocyte function antigen LFA-1 were identified immunohistochemically. VCAM-1, ICAM-1, and E-selectin were equally or less expressed, whereas P-selectin was increased on microvessels in tumour tissue. The density of VCAM-1-positive tumour microvessels correlated positively with an advanced tumour stage and E- and P-selectin-positive tumour microvessels with the amount of associated macrophages. The expression of ICAM-1 and VCAM-1 on neoplastic epithelia correlated with an increased density of macrophages and a minor degree of tumour differentiation. Conclusions The positive correlation of macrophage infiltration and expression of cell adhesion molecules on tumour microvessels and epithelia with minor tumour differentiation and an advanced stage indicates that adhesion molecule expression is not associated with an effective antitumour function of macrophages [source]

Expression and enzyme activity of ,(1,6)fucosyltransferase in human colorectal cancer

Laura Muinelo-Romay
Abstract Changes in enzyme activity and the expression levels of ,(1,6)fucosyltransferase [,(1,6)FT] have been reported in certain types of malignant transformations. To develop a better understanding of the role of ,(1,6)FT in human colorectal carcinoma (CRC), we analysed the enzyme activity in healthy and tumour tissues. ,(1,6)FT activity was considerably higher in tumour tissue than in healthy tissue and was related to gender, lymph node metastasis, type of growth and tumour stage. We also observed a significant increase in the ,(1,6)FT expression in tumour tissues as compared to healthy and transitional tissues, inflammatory lesions and adenomas. The immunohistochemical expression in tumour tissues was correlated with the degree of infiltration through the intestinal wall. Finally, a statistical correlation was found between enzyme activity and expression obtained by Western blot in colorectal tumours when compared in the same patient. All these findings demonstrate an alteration of ,(1,6)FT activity and expression in CRC. © 2008 Wiley-Liss, Inc. [source]

Monitoring indicators of health care quality by means of a hospital register of tumours

Maximino Redondo MD PhD
Abstract Rationale, Hospital registers of tumours provide, on a continuous basis, information on differences in patterns of neoplasias and the results of the treatment strategies employed. Objective, In view of the scant publications on measures of health care quality in hospital tumour registers, the aim of our paper is to present the outcome of a study to monitor the results related to health care quality in oncology. Methods, Data are presented for cases recorded at the Hospital Costa del Sol over a period of 8 years. The sources of information are fundamentally the patient's medical record and the database of the Pathology Department. Results, A high proportion of patients (mean 50%, range 45,68%) were admitted to the hospital by the Emergency Department; there was a notably long delay between the appearance of the first symptoms and the occasion of the first hospital visit (median 65 days; range 60,75 days). Particularly striking was the corresponding delay for breast cancer patients, in most cases superior to 3 months. As was the case for the percentage of admissions by the Emergency Department, most of the indicators evaluated in this study present a significant improvement compared with the initial years of the Hospital Register of Tumours. Thus, non anatomic-pathological diagnoses represented around 7% (range 3,13%), while 43% of patients (range 28,57%) were given adjuvant treatment in the form of radiation therapy or chemotherapy. In 40% of cases (range 20,50%), the tumour stage was included in the clinical record by the doctor who was treating the patient (in the remaining cases, these data were recorded by the Tumour Registry); the date of appearance of the first symptoms was included in the medical record in 65% of cases (range 54,80%). According to the stage classification, the following 5-year survival rates were recorded: (I) 98%, (II) 94%, (III) 69% and (IV) 39% for breast cancer; (I) 93%, (II) 83%, (III) 68% and (IV) 12% for cancer of the colon; and (I) 100%, (II) 94%, (III) 79% and (IV) 53% for prostate cancer. Conclusion, The high percentage of patients admitted by the Emergency Department and the long delay between the appearance of the first symptoms reflect the deficient attention paid to this problem by patients and by primary health care services. Our results suggest that the Hospital Register of Tumours could constitute an excellent tool for monitoring the quality of health care systems for oncological patients. [source]

Radical radiotherapy with high-dose-rate brachytherapy for uterine cervix cancer long-term results,

TH Khor
Summary The aim of this is to report the results of radical radiotherapy in carcinoma of the cervix treated by high-dose rate (HDR) intracavitary brachytherapy and external beam radiotherapy (XRT) at a single centre in Singapore. This is a retrospective analysis of 106 consecutive cases with histologically proven cervical cancer, treated by HDR brachytherapy and XRT at the Mount Elizabeth Hospital from 1990 to 1993. External beam radiotherapy to the pelvis was delivered with 6 MV photons, to 45,50.4 Gy in 1.8 Gy fractions. High-dose-rate brachytherapy comprised two to three applications of an intrauterine tandem with paired ovoids, to a median dose of 18 Gy to point ,A', carried out during XRT. All 106 patients completed treatment. Their ages ranged from 32 to 80 years (median 57 years). Most patients presented with stage II or III disease (44 and 37%, respectively) and with squamous cell carcinoma (91%). Median follow-up time was 59 months (range 2,169 months). The 5-year relapse-free survival rate across all stages was 71%. The corresponding overall survival rate was 69%. Local control was achieved in 86 patients (81%); six patients had residual disease (6%), and 14 patients had local recurrence (13%). Fourteen patients developed metastatic disease (13%). On univariate analysis, tumour stage, haemoglobin level, number of brachytherapy treatments and overall treatment time were found to be prognostic factors for overall survival. Late complications were mild (Radiation Therapy Oncology Group score 1,2), except for one patient with grade 4 rectal toxicity. The complication rates were 8, 14 and 45%, respectively, for the rectum, bladder and vagina (stenosis). The use of two to three fractions of HDR intracavitary brachytherapy in addition to pelvic XRT achieves good outcomes. [source]

Impact of primary tumour stage on survival in dogs with solitary lung tumours

G. A. Polton
Objectives: The objective of this study was to determine simple prognostic criteria for differentiation of canine solitary lung tumour cases into those that will and will not benefit from thoracic surgery. Methods: This was a retrospective study using the records of cases presented to Davies Veterinary Specialists, Hitchin, UK, from December 1998 to December 2005. Survival analyses were performed using the Kaplan-Meier and logrank methods. Potentially significant variables were evaluated by multivariate Cox analysis. Results: Forty-two patients met the inclusion criteria. Primary tumour stage T1, absence of neoplastic lymph nodes and metastases, and papillary tumour type were statistically significant favourable prognostic indicators on univariate analysis. Multivariate analysis attributed significance to primary tumour stage T1 and papillary type only. Median survival times were 555 days for T1N0M0 tumours of papillary type and 72 days for the remainder. Clinical Significance: Survival time following surgery in dogs with primary lung tumours was poor except in clinical stage T1N0M0 cases. These data support use of clinical techniques to dichotomise cases as T1N0M0 or other, improving decision making in thoracic surgery. These data validate initiation of prospective studies examining the role of chemotherapy in the management of advanced cases. [source]

Mycosis fungoides presenting with extensive pyoderma gangrenosum-like ulcers

SG Carbia
Abstract Mycosis fungoides (MF) may present with atypical clinical manifestations. Usually it mimics various chronic dermatoses, with the appearance of ulcers during the tumour stage. Infrequently, cutaneous ulcers are the main or initial sign of lymphoma. We report the case of a man who presented multiple skin lesions that clinically appeared to be pyoderma gangrenosum (PG). However, histological and immunohistochemical examination revealed MF. This case illustrates that PG-like ulcers may be atypical cutaneous manifestations of MF and exceptionally the presenting sign of this disease. [source]

Discovery of myopodin methylation in bladder cancer,

V Cebrian
Abstract Myopodin is an actin-binding protein that shuttles between the nucleus and the cytoplasm. After identifying an enriched CpG island encompassing the transcription site of myopodin, we aimed at evaluating the potential relevance of myopodin methylation in bladder cancer. The epigenetic silencing of myopodin by hypermethylation was tested in bladder cancer cells (n = 12) before and after azacytidine treatment. Myopodin hypermethylation was associated with gene expression, being increased in vitro by this demethylating agent. The methylation status of myopodin promoter was then evaluated by methylation-specific polymerase chain reaction (MS-PCR) analyses. Myopodin was revealed to be frequently methylated in a large series of 466 bladder tumours (68.7%). Myopodin methylation was significantly associated with tumour stage (p < 0.0005) and tumour grade (p = 0.037). Myopodin expression patterns were analysed by immunohistochemistry on tissue arrays containing bladder tumours for which myopodin methylation was assessed (n = 177). The presence of low nuclear myopodin expression alone (p = 0.031) or combined with myopodin methylation (p = 0.008) was associated with poor survival. Moreover, myopodin methylation in 164 urinary specimens distinguished patients with bladder cancer from controls with a sensitivity of 65.0%, a specificity of 79.8%, and a global accuracy of 75.3%. Thus, myopodin was identified to be epigenetically modified in bladder cancer. The association of myopodin methylation and nuclear expression patterns with cancer progression and clinical outcome, together with its ability to detect bladder cancer patients using urinary specimens, suggests the utility of incorporating myopodin methylation assessment in the clinical management of patients affected by uroepithelial neoplasias. Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [source]

FGFR3 protein expression and its relationship to mutation status and prognostic variables in bladder cancer,

DC Tomlinson
Abstract FGFR3 is frequently activated by mutation in urothelial carcinoma (UC) and represents a potential target for therapy. In multiple myeloma, both over-expression and mutation of FGFR3 contribute to tumour development. To define the population of UC patients who may benefit from FGFR-targeted therapy, we assessed both mutation and receptor over-expression in primary UCs from a population of new patients. Manual or laser capture microdissection was used to isolate pure tumour cell populations. Where present, non-invasive and invasive components in the same section were microdissected. A screen of the region of the highest tumour stage in each sample yielded a mutation frequency of 42%. Mutations comprised 61 single and five double mutations, all in hotspot codons previously identified in UC. There was a significant association of mutation with low tumour grade and stage. Subsequently, non-invasive areas from the 43 tumours with both non-invasive and invasive components were analysed separately; 18 of these had mutation in at least one region, including nine with mutation in all regions examined, eight with mutation in only the non-invasive component and one with different mutations in different regions. Of the eight with mutation in only the non-invasive component, six were predicted to represent a single tumour and two showed morphological dissimilarity of fragments within the block, indicating the possible presence of distinct tumour clones. Immunohistochemistry showed over-expression of FGFR3 protein in many tumours compared to normal bladder and ureteric controls. Increased expression was associated with mutation (85% of mutant tumours showed high-level expression). Overall, 42% of tumours with no detectable mutation showed over-expression, including many muscle-invasive tumours. This may represent a non-mutant subset of tumours in which FGFR3 signalling contributes to the transformed phenotype and which may benefit from FGFR-targeted therapies. Copyright © 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [source]

Morphological features of TMPRSS2,ERG gene fusion prostate cancer,

J-M Mosquera
Abstract The TMPRSS2,ETS fusion prostate cancers comprise 50,70% of the prostate-specific antigen (PSA)-screened hospital-based prostate cancers examined to date, making it perhaps the most common genetic rearrangement in human cancer. The most common variant involves androgen-regulated TMPRSS2 and ERG, both located on chromosome 21. Emerging data from our group and others suggests that TMPRSS2,ERG fusion prostate cancer is associated with higher tumour stage and prostate cancer-specific death. The goal of this study was to determine if this common somatic alteration is associated with a morphological phenotype. We assessed 253 prostate cancer cases for TMPRSS2,ERG fusion status using an ERG break-apart FISH assay. Blinded to gene fusion status, two reviewers assessed each tumour for presence or absence of eight morphological features. Statistical analysis was performed to look for significant associations between morphological features and TMPRSS2,ERG fusion status. Five morphological features were associated with TMPRSS2,ERG fusion prostate cancer: blue-tinged mucin, cribriform growth pattern, macronucleoli, intraductal tumour spread, and signet-ring cell features, all with p -values < 0.05. Only 24% (n = 30/125) of tumours without any of these features displayed the TMPRSS2,ERG fusion. By comparison, 55% (n = 38/69) of cases with one feature (RR = 3.88), 86% (n = 38/44) of cases with two features (RR = 20.06), and 93% (n = 14/15) of cases with three or more features (RR = 44.33) were fusion positive (p < 0.001). To our knowledge, this is the first study that demonstrates a significant link between a molecular alteration in prostate cancer and distinct phenotypic features. The strength of these findings is similar to microsatellite unstable colon cancer and breast cancer involving BRCA1 and BRCA2 mutations. The biological effect of TMPRSS2,ERG overexpression may drive pathways that favour these common morphological features that pathologists observe daily. These features may also be helpful in diagnosing TMPRSS2,ERG fusion prostate cancer, which may have both prognostic and therapeutic implications. Copyright © 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [source]

Expression of the nm23 homologues nm23-H4, nm23-H6, and nm23-H7 in human gastric and colon cancer

M Seifert
Abstract Eight members of the nm23-gene family have been described. The involvement of nm23-H1 and nm23-H2 in tumour progression and metastasis, as well as in gene regulation and apoptosis, has been shown in numerous studies. Whether nm23-H4, -H6, and -H7 play a role in tumours is, however, largely unknown. This study describes data on the expression of these three nm23 homologues in human colon and gastric cancer by real-time RT-PCR and immunohistochemistry. Increased expression of these genes, most strikingly nm23-H4 and -H7, was observed in the majority of tumours analysed. No correlation with tumour stage according to the TNM classification was found. In contrast, by immunohistochemical analysis, nm23-H4 and -H6 overexpression correlated with the intestinal tumour type in gastric cancer tissues, whereas no increased immunoreactivity for the three nm23 proteins was noted in the diffuse type tumour specimens. These findings indicate that nm23-H6, and particularly nm23-H4 and -H7, may be involved in the development of colon and gastric carcinoma, the latter possibly in a type-specific manner. A contribution to tumour progression or metastasis could not, however, be proven. Elucidation of the specific mechanisms by which the nm23 homologues nm23-H4, -H6, and -H7 are involved in tumour development requires further studies. Copyright © 2005 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [source]

Pancreaticoduodenectomy , outcomes from an Australian institution

Kelvin H.K. Kwok
Abstract Background:, Operative morbidity and mortality rates have improved markedly since the first single-stage pancreaticoduodenectomy (PD) was performed by A. O. Whipple in 1940. There is a lack of published data regarding outcomes of PD from Australian centres. The aim of this study was primarily to establish post-operative morbidity and mortality rates of an Australian unit, and secondly, to investigate the value of preoperative investigation with endoscopic ultrasound and laparoscopy upon tumour stage and survival following PD. Method:, A retrospective analysis was conducted on consecutive patients undergoing PD at St Vincent's Hospital from 1990 to 2006. Data were collected with particular reference to preoperative investigations, including endoscopic ultrasonography (EUS) and staging laparoscopy, and post-operative complications. Patient survival was determined from the hospital and consultant surgeons' records and telephone interviews with the patients' general practitioners. Results:, Eighty-one patients underwent PD, of which 58 were Whipple's procedures and 23 were pylorus-preserving pancreaticoduodenectomies (PPPD). Twenty-six patients had EUS, and 22 had a staging laparoscopy before PD. The post-operative morbidity rate was 55% and included intra-abdominal collections (17%), major haemorrhage (10.7%), pancreatic anastomotic leakage (9%) and delayed gastric emptying (22%). The operative (30-day) mortality rate was 1.6%. There was no survival advantage in the EUS or the laparoscopy group. Conclusion:, EUS and laparoscopy are useful modalities in the preoperative investigation and staging of patients being considered for PD. PD is a safe procedure with acceptable complication rates when carried out in a specialist unit experienced in this operation. [source]

The impact of volume on outcomes after oesophageal cancer surgery

Ioannis Rouvelas
Abstract Oesophageal cancer is an aggressive disease with a poor prognosis. Oesophagectomy is an established, potentially curative treatment, for patients with resectable oesophageal cancer. The anatomical location of the oesophagus explains why this type of operation is one of the most demanding and traumatic surgical procedures undertaken in general surgery. Unfortunately, the risk for severe post-operative complications is high and the chance for cure remains low. It is, however, encouraging that the post-operative morbidity has been decreasing and the survival has been improving during recent years. Several factors might have contributed to this improvement, including the centralization of oesophageal cancer surgery to high volume centres. This review focuses on the impact of hospital and surgeon volume on various outcomes after oesophagectomy for oesophageal cancer. Most available research indicates that, as far as post-operative complications, early post-operative mortality and health economics after oesophagectomy are concerned, high surgery volume is to be recommended, while the few studies evaluating long-term survival and health-related quality of life adjusted for tumour stage found no evidence of a role for volume. In conclusion, the available literature supports the centralization of oesophagectomy for cancer to dedicated centres with a multidisciplinary approach and a good track record of valid clinical research. [source]

Impact of laparoscopic surgery on the long-term outcomes for patients with rectal cancer

Jun-Gi Kim
Abstract Background:, This 20-year retrospective study compared the results of laparoscopic surgery with open surgery for patients with rectal cancer to evaluate the impact of laparoscopic surgery on long-term oncological outcomes for rectal cancer. Methods:, We analysed survival data collected over 20 years for patients with rectal cancer (n= 407) according to surgical methods and tumour stage between those treated with laparoscopic surgery (n= 272) and those with open surgery (n= 135). Clinical factors were analysed to ascertain possible risk factors that might have been associated with survival from and recurrence of rectal cancer. A multivariate analysis was applied by using Cox's regression model to determine the impact of laparoscopic surgery on long-term oncological outcomes. Results:, Overall survival, disease-specific survival and disease-free survival rates were statistically higher in the laparoscopic group than in the open-surgery group. The incidence of local recurrence in the laparoscopic group (7.9%; 95% confidence intervals (CI), 4.2,11.5) was significantly lower than that for the open-surgery group (30.2%; 95% CI, 21.0,39.3; P < 0.001). By using a multivariate analysis, laparoscopic surgery for rectal cancer appeared not to be an independent factor for disease-specific survival or disease-free survival. However, the laparoscopic surgery was an independent factor associated with reduced local recurrence (Hazard ratio (HR), 3.408; 95% CI, 1.890,6.149; P < 0.001). Conclusion:, Laparoscopic surgery did not adversely affect the long-term oncological outcome for patients with rectal cancer. [source]

Model for collecting colorectal cancer staging information in Western Australia

Padabphet Boutard
Background: There is recognition that to improve the management of patients with cancer we need to monitor outcomes, especially survival outcomes based on tumour stage. Unfortunately, there are few centres in Australia that can provide stage stratified survival information, despite the large investments that have been made in data collection. The aim of this study was to collect staging information for all colorectal cancers diagnosed in Western Australia over a 12-month period. This information could then serve as a basis for more meaningful analysis. Methods: A project officer was appointed to coordinate a programme through the Western Australian Cancer Registry. A consensus was reached among pathologists on the standardized reporting of colorectal cancers to the registry. Clinicians were asked to provide, on pathology request forms, information on tumour location, the presence of metastatic disease (on X-ray or at laparotomy), and type of surgery. Use was also made of existing hospital and unit based databases to acquire and crosscheck information. Results: Over a 12-month study period, 1008 patients with colorectal cancers were notified to the Cancer Registry. Their mean age was 69.1 years (range 23,100 years), 56% were men and 44% women. The rectum was the most common site for disease location (32.5%). At cessation of the project, 743 patients (74%) were fully staged, with a further 221 patients (22%) having completed data on tumour depth of penetration and nodal status, but insufficient information on the presence of metastases. The stage distributions were: stage I , 20.5%; stage II , 29.9%; stage III , 26.2%; stage IV , 23.4%. Conclusions: It is feasible to collect staging information on colorectal cancers notified to a population based cancer registry. This information will be invaluable for stage stratified survival analysis and research. [source]


D. Mccombe
Background: Squamous cell carcinoma (SCC) of the lower lip is a common malignancy in Australia. Surgical excision and/or radiotherapy are used in treatment, and are regarded as equally effective. Methods: A retrospective review of 323 patients treated at the Peter MacCallum Cancer Institute with either surgical excision and/or radiotherapy, evaluated disease recurrence, cause-specific mortality, and the incidence of metachronous lesions. Results: Recurrence-free survival at 10 years was estimated to be 92.5%, and cause-specific survival at 10 years was estimated to be 98.0%. Equivalent rates of local control were obtained with surgery and radiotherapy. Recurrence was related to tumour stage and differentiation. A high incidence of metachronous lesions was noted, 25 patients had a lesion prior to presentation and 33 patients developed second lip lesions during the study period. Conclusions: Squamous cell carcinoma of the lower lip is well treated with surgery or radiotherapy. The preferred treatment for most patients with SCC of the lower lip in the Australian population is surgical excision. This study has shown a significant incidence of metachronous lip neoplasia, except in those patients whose whole lip had been resurfaced. [source]

Laparoscopic restaging of borderline ovarian tumours: results of 30 cases initially presumed as stage IA borderline ovarian tumours

D. Querleu
Objectives To review our experience with the laparoscopic restaging procedure of presumed early stage borderline ovarian tumours. Design Retrospective study. Setting Cancer centre. Population Thirty patients with presumed stage I borderline ovarian tumours after limited initial surgery Methods From April 1991 to May 2001, the patients were laparoscopically reassessed. The procedure involved peritoneal cytology, exploration of the peritoneal cavity, infracolic omentectomy, directed or random peritoneal biopsies, and when appropriate, contralateral oophorectomy and hysterectomy and appendectomy. Medical records were reviewed for patients' age, interval time between procedures, tumour stage, histological type, operative time, hospital stay, peri-operative complications and follow up. Main outcome measures Seroperative and postoperative data, pathology and clinical follow up. Results Laparoscopic restaging was completed in all 30 (100%) identified patients. The mean age was 34.8 (10.5) years; the delay between initial operation and restaging laparoscopy averaged 9.8 (6.6) weeks. The mean operative time was 165.4 (53.8) minutes, and the mean hospital stay was 2.7 (1.3) days. There were two (7.0%) major complications related directly to the procedure. Eight (26.6%) patients were upstaged. Mean follow up was 29.1 (6.6) months, all patients are alive and one (3.2%) recurrence was observed. Conclusions Laparoscopic approach of restaging for borderline ovarian tumours is an accurate safe procedure. It is associated with an acceptable rate of minor complications, it has similar morbidity associated with laparotomy and it minimises the incidence of infertility in the young patients. Whenever staging of borderline ovarian tumours is to be considered in an individual patient, laparoscopy provides a suitable alternative approach. [source]

The number of negative pelvic lymph nodes removed does not affect the risk of biochemical failure after radical prostatectomy

Alana M. Murphy
Study Type , Therapy (case series) Level of Evidence 4 OBJECTIVES To assess patients who had radical prostatectomy (RP) and pelvic lymph node dissection (PLND) for pT2,4 N0M0 prostate cancer, to determine if LN yield affects the risk of biochemical failure (BCF), as the extent of PLND at the time of RP has become increasingly uncertain with the decreasing trend in tumour stage. PATIENTS AND METHODS We reviewed the Columbia University Urologic Oncology Database for patients with pT2,4 N0M0 prostate cancer treated with RP from 1990 to 2005. Exclusion criteria included <12 months of follow-up, incomplete clinical and pathological data, and neoadjuvant androgen-deprivation therapy (ADT) or immediate adjuvant ADT or external beam radiotherapy. Unadjusted and adjusted models were used to determine the ability of clinical and pathological variables to predict BCF. RESULTS The final dataset included 964 patients, with a mean age of 60.5 years and median preoperative prostate-specific antigen (PSA) level of 6.2 ng/mL. The median (range) LN yield was 7 (1,42) and the median follow-up 59 (12,190) months. In the unadjusted and adjusted models, preoperative PSA, pathological Gleason score, pathological stage, surgical margin status and year of surgery were significant predictors of BCF. The LN group was not a significant predictor of BCF in both the unadjusted and adjusted model (P = 0.759 and 0.408, respectively). When patients were stratified into high- and low-risk groups, LN yield remained an insignificant predictor of BCF. CONCLUSION A higher LN yield at the time of RP does not increase the chance of cure for patients with pT2,4N0M0 prostate cancer. This lack of a survival advantage holds true for patients with high-risk disease. [source]

Oncological control after radical prostatectomy in men with clinical T3 prostate cancer: a single-centre experience

Evanguelos Xylinas
OBJECTIVE To determine the effectiveness of cancer control afforded by radical prostatectomy (RP) in patients with clinical stage T3 prostate cancer. PATIENTS AND METHODS We retrospectively reviewed data for patients treated by RP for clinical stage T3 prostate cancer between 1995 and 2005. The following case characteristics were analysed: patient age, clinical presentation, preoperative prostate-specific antigen (PSA) level, Gleason score, tumour stage (2002 Tumour-Node-Metastasis), surgical procedure, pathological data, margin and lymph node status, and recurrence. Biochemical recurrence was defined as an increase in PSA level of >0.2 ng/mL after surgery. Kaplan-Meier survival curves were generated, and prognostic factors were evaluated. RESULTS Overall, 100 patients were included; only 79% of them had pT3 disease based on the pathological specimen. The median follow-up after RP was 69 months. The RP was open in 77 and laparoscopic in 23, with no significant difference between these approaches (P = 0.38). The 5-year PSA-free survival after surgery was 45%, and 5-year cancer-specific survival was 90%. On univariable analysis, Gleason score >7 (P = 0.01), pathological stage (pT2-T3a vs T3b) (P < 0.001), positive lymph node (P < 0.001), and positive margin (P < 0.001) were associated with recurrence. On multivariable analysis, lymph node, margin status and Gleason score were also significant (P < 0.05). CONCLUSIONS RP can be recommended as an alternative primary treatment that results in acceptable cancer control for clinical stage T3 prostate cancer in selected cases. However, the patient should be warned that surgery alone might not be sufficient to control the cancer, and that adjuvant therapy might be needed during the course of the disease. [source]

Does the current World Health Organization classification predict the outcome better in patients with noninvasive bladder cancer of early or regular onset?

Maximilian Burger
OBJECTIVE To compare the clinical outcome and prognostic power of the former and current World Health Organization (WHO) grading system in patients with early vs regular onset of noninvasive urothelial bladder cancer (UBC), as little is known of the natural history of early onset UBC and in how far it is reflected by histopathological grading and staging in guiding clinical decisions. PATIENTS AND METHODS The medical records of 69 consecutive patients presenting with initial UBC of early onset (,45 years old, EO) and of 100 randomly chosen patients with regular onset (RO) were reviewed. There were no significant differences in gender distribution, risk factors or tumour stage. All histopathological specimens were re-staged and re-graded according to the former and current WHO grading. RESULTS In all, 51 EO and 63 RO patients with tumours staged pTa and complete follow-up information were analysed. Recurrence-free survival (RFS) was prolonged in patients with EO. In EO neither the former nor the current WHO grading system was significantly related to RFS or to progression to muscle-invasive disease. In RO, while both WHO grading systems were significantly related to RFS, only the current WHO grading system was related to progression. CONCLUSION While larger studies are needed, UBC in patients with EO and RO do not seem to differ in risk factors and oncological outcome. The current WHO classification reflects the outcome more accurately than the former classification in patients with RO. However, for EO no grading system has sufficient prognostic power and novel methods, i.e. molecular markers, need to be evaluated for clinical use. [source]

Relation of microvessel density with microvascular invasion, metastasis and prognosis in renal cell carcinoma

Esin Yildiz
OBJECTIVE To clarify the significance of microvessel density (MVD) in a retrospective investigation the relationship between the pattern of MVD (reflecting angiogenesis), and tumour stage, grade, size, and occurrence of microvessel invasion (MVI), metastasis, and cancer-specific survival (CSS) in patients who had surgery for renal cell carcinoma (RCC). PATIENTS AND METHODS Vessels were labelled in sections of formalin-fixed, paraffin-embedded tissues from 54 RCCs by CD34 immunohistochemistry. The mean MVD, expressed as the number of vessels per 10 high-power fields (HPF, ×400) were measured for each case. In addition, all pathological slides were reviewed for the presence and absence of MVI. The prognostic value of MVD and MVI was then evaluated, and correlated with the usual prognostic variables, tumour metastasis and CSS. RESULTS In a univariate analysis of CSS, the MDV tended to be lower as stage increased from pT1 to pT3, and as grade increased from G1 to G4, although it was statistically significant only for stage (P < 0.001 and 0.050, respectively). The mean MVD was higher in 42 nonmetastatic than in 12 metastatic tumours, and in 33 tumours associated with MVI than in 21 with no MVI (P < 0.001). The mean MVD was also lower and significantly different for 28 large than 26 small tumours (P = 0.005). The survival rate of patients with tumours that were small, low-stage, of higher MVD, with no MVI and metastasis was significantly higher than that of patients with large, high-stage, low MVD, with MVI and metastatic tumours (all P < 0.001). MVI was significantly more common with a decreasing trend in MVD and the presence of metastasis (Spearman rank correlation rs = ,0.68, P = 0.01, and rs = 0.39, P = 0.01, respectively). Independent prognostic factors in a multivariate analysis were: in all patients with RCC, tumour stage (P = 0.013) and metastasis (P = 0.028); in those with low MVD, MVI (P = 0.004) and metastases (P = 0.016); in those with no MVI, stage (P = 0.020); in those with MVI, MVD (P = 0.001); in those with no metastases, stage (P = 0.045); and in those with metastases, MVD (P < 0.001). No independent predictor was identified in patients with high MVD. In patients with no metastases there was a significantly shorter median CSS time in RCCs with low MVD and with MVI (P = 0.004 for both). Similarly, patients who had grade 3,4 tumours, vs those with lower MVD and with MVI, had a significantly shorter median CSS (P = 0.020 for MVD, and 0.01 for MVI). CONCLUSIONS This study suggested that MVD in RCC was inversely associated with MVI, tumour metastasis, patient survival and tumour diameter and stage, from the usual prognostic variables, but MVD was not an independent prognostic factor in multivariate analysis for all patients with RCC. Low MVD and the presence of MVI appears to be a marker for identifying patients with an adverse prognosis. [source]

Predicting outcome in minimally invasive (T1a and T1b) urothelial bladder carcinoma using a panel of biomarkers: a high throughput tissue microarray analysis

Paulette Mhawech-Fauceglia
OBJECTIVE To evaluate the protein expression of fibroblast growth factor receptor-3 (FGFR3), hamartin, 14-3-3,, Aurora-A, and E-cadherin using immunohistochemistry (IHC) in a series of human bladder carcinomas and to evaluate their value in distinguishing T1a from T1b tumours and in predicting their behaviour, as T1 urothelial bladder tumours present great diagnostic and therapeutic challenges to pathologists and clinicians. PATIENTS, MATERIALS AND METHODS Tissue microarrays were constructed from 94 patients (Ta 20, T1a 31, T1b 14, and T2 29 patients) using tissue obtained at first disease presentation. RESULTS FGFR3 and 14-3-3, were the only markers that were significantly associated with tumour grade and 14-3-3, was significantly associated with tumour stage. Furthermore, none of these markers could help in distinguishing T1a from T1b tumours. After adjusting for the E-cadherin expression, FGFR3 expression was a significant factor in predicting the time to recurrence in T1a/T1b. Furthermore, among all the clinical variables, grade and depth of invasion were the only ones that had a significant value in predicting T1a/T1b tumour progression. CONCLUSIONS Even though the staging of T1 to T1a/T1b is not a common practice and it is not included in the Tumour-Node-Metastasis classification, our data clearly confirmed the importance of a proper sub-staging of T1 tumours whenever feasible. [source]

Different vascular endothelial growth factor (VEGF), VEGF-receptor 1 and -2 mRNA expression profiles between clear cell and papillary renal cell carcinoma

OBJECTIVES To examine vascular endothelial growth factor (VEGF), VEGF-receptor-(R)1, and R2 mRNA levels in renal cell carcinoma (RCC), a tumour generally refractory to most medical therapy, but for which a potentially useful therapeutic alternative is inhibition of angiogenesis. PATIENTS AND METHODS VEGF, VEGF-R1 and -R2 mRNA levels were analysed using the quantitative reverse transcription-polymerase chain reaction. RNA was extracted from 84 conventional (clear cell) RCCs (cRCC), 20 papillary (pRCC), six chromophobe (chRCC), and 27 corresponding kidney cortex tissues, obtained from 110 patients in whom high-quality RNA was available from the tumours (53 women and 57 men, mean age 64.7 years, range 25,85). RESULTS The VEGF, VEGF-R1, and -R2 mRNA levels were higher in tumour than in kidney cortex tissues. Among the RCC types, cRCC had higher VEGF levels than pRCC. In cRCC, VEGF-R2 levels were higher in stage I,II than in more advanced stages. In pRCC, VEGF and VEGF-R2 levels were higher in stage III than in stage I,II tumours. In cRCC, patients with VEGF levels below the median had a significantly shorter survival time than those with higher levels. By contrast, in pRCC, VEGF, VEGF-R1 and -R2 RNA levels above the median were related to adverse survival. Using multivariate analysis in cRCCs, VEGF-R1 mRNA level was the last factor to be omitted after stepwise elimination analysis. CONCLUSION VEGF and its receptors were associated with tumour stage and survival, but were not independent prognostic factors. Different RCC types had different expression patterns of VEGF and receptor mRNA levels. We conclude that different pathways might be involved in regulating angiogenesis in the specific RCC types. Detailed knowledge of angiogenesis in RCC is essential when designing new treatment trials where angiogenesis inhibition is used. [source]

Telomerase activity in disseminated prostate cancer cells

OBJECTIVE To analyse telomerase activity in disseminated prostate cancer cells isolated from bone marrow aspirates taken from men with localized prostate cancer before radical prostatectomy (RP). PATIENTS AND METHODS Disseminated epithelial prostate cancer cells were isolated from bone marrow aspirates from 69 men with localized prostate cancer before RP, by magnetic column-chromatography enrichment, followed by isolation of fluorescently labelled epithelial cells by micropipetting. We used pools of 10 non-epithelial bone marrow cells after tumour cell enrichment as control samples. These pure cell pools were tested for the presence of telomerase activity. RESULTS In all, 49 of the patient samples contained disseminated prostate cancer cells. Homogeneous pools of 10 cells were obtained from 35 of these; 49% of the 35 specimens showed telomerase activity, whereas all five control samples did not. Telomerase activity in the 35 samples was not significantly associated with Gleason score, preoperative prostate-specific antigen level, tumour stage, or surgical margin status. Follow-up is continuing to assess an association with disease recurrence. CONCLUSION This work shows the feasibility of isolating disseminated cancer cells for analysing individual or pooled cells. Compared to tissue staining, where telomerase is detected in 80,90% of samples, we found lower rates of telomerase activity in the disseminated tumour cells (49%). Telomerase-negative cells might provide information about cell dormancy, as telomerase is a marker of cell proliferation in immortal and cancer cells. Telomerase-positive cells might predict early disease recurrence, but a longer follow-up is needed to test this possibility. [source]

A single-nucleotide polymorphism in the XPG gene, and tumour stage, grade, and clinical course in patients with nonmuscle-invasive neoplasms of the urinary bladder

OBJECTIVE To evaluate whether the single nucleotide polymorphism (SNP), Asp1104His (G3507C), in the XPG gene affects malignant phenotypes of nonmuscle-invasive urinary bladder neoplasms (NIBN), by investigating associations between the SNP and clinicopathological variables in patients with NIBN. PATIENTS AND METHODS The 233 patients constituted newly diagnosed cases of primary NIBN in the Stockholm area. The Asp1104His polymorphism in the XPG gene was genotyped using a polymerase chain reaction-restriction fragment length polymorphism technique. RESULTS The GC + CC genotypes were more frequent in stage pT1 tumours at initial diagnosis than pTa (odds ratio 1.9, 95% confidence interval 1.0,3.5, P = 0.048). The difference was larger in the young group (4.6, 1.9,11.8, P = 0.001). In the young group, the GC + CC genotypes were significantly more frequent in high-grade than in low-grade tumours (3.1, 1.5,6.8, P = 0.004) whereas in the older group the genotypes were less frequent in high-grade tumours (0.3, 0.1,0.7, P = 0.007). The XPG genotypes were not associated with tumour recurrence, stage progression or survival. CONCLUSION These results suggest that the SNP in the XPG gene might be related to tumour invasiveness in NIBN. [source]

Plasma osteopontin levels are predictive of disease stage in patients with transitional cell carcinoma of the bladder

Celina Ang
OBJECTIVE To measure plasma levels of osteopontin in patients with transitional cell carcinoma (TCC) of the bladder, and to determine if osteopontin levels relate to disease stage. PATIENTS AND METHODS Blood samples were collected from 72 consecutive patients with TCC. Clinical data were obtained from medical record reviews. Patients were divided into subgroups based on disease status (active vs inactive) and clinical and pathological stage of TCC (tumour, nodes and metastases staging system). Osteopontin levels were measured using an enzyme-linked immunosorbent assay. RESULTS Plasma osteopontin levels were higher in patients with active TCC than in controls (P = 0.035). Plasma osteopontin levels were not significantly different between patients with active and inactive TCC, but were higher in patients with metastases than in patients with active, clinically organ-confined TCC (P = 0.021). CONCLUSIONS Plasma osteopontin levels increase with tumour stage in TCC of the bladder. These findings suggest that larger, more extended studies on plasma osteopontin levels in patients with TCC are warranted. [source]

A clinicopathological study of the expression of extracellular matrix components in urothelial carcinoma

Elli Ioachim
OBJECTIVE To measure the immunohistochemical expression of the extracellular matrix (ECM) components tenascin, fibronectin, collagen type IV and laminin in urothelial carcinomas, and to correlate their expression with clinicopathological features to clarify the prognostic value of these molecules and their role in tumour progression. MATERIALS AND METHODS Tumour specimens obtained during transurethral resection of bladder tumour (TURBT) from 103 patients (82 men and 2 1 women, mean age 66.7 years, range 27,89) were studied retrospectively. The expression of tenascin, fibronectin, collagen type IV and laminin was correlated with clinicopathological features (tumour grade and stage, multiplicity, simultaneous in situ component, the proliferative activity as estimated by the two proliferation associated indices, Ki-67 and proliferating cell nuclear antigen, the recurrence rate, and the progression of invading tumour). Specimens investigated for tenascin expression from patients with superficial bladder cancers were categorized into 28 treated by TURBT only and 53 who had TURBT followed by intravesical instillations of interferon. RESULTS Cytoplasmic tenascin expression was detected in tumour cells in 20% of specimens. Tenascin was expressed in the tumour stroma in 76% of specimens, and was positively correlated with tumour grade and stage. Stromal tenascin expression was positively correlated with proliferative activity, and with the expression of fibronectin and collagen type IV. Fibronectin was expressed in the tumour stroma in 89% of specimens and was positively correlated with tumour stage, proliferative activity, and expression of collagen type IV and laminin. Collagen type IV was expressed in 93% of specimens, and was positively correlated with tumour grade and stage. Laminin was expressed in 78% of specimens and had no significant correlation with the clinicopathological features. Patients treated with TURBT alone and who had low levels of tenascin had a longer tumour-free interval than those with high levels of tenascin. CONCLUSION Levels of tenascin might be valuable for predicting the risk of early recurrence. The expression of tenascin, fibronectin and collagen type IV seems to be correlated with more aggressive tumour behaviour. Furthermore, their interrelationships could indicate that they are involved in the remodelling of bladder cancer tissue, probably influencing tumour progression. [source]

Prognostic value of the expression of Ki-67, CD44 and vascular endothelial growth factor, and microvessel invasion, in renal cell carcinoma

E. Yildiz
OBJECTIVE To determine if use of cell proliferation, cell adhesion, level of angiogenesis-related factors and presence of microscopic vascular invasion (MVI) could better predict the biological behaviour of renal cell carcinoma (RCC), which has a widely variable clinical outcome despite the use of conventional prognostic factors (staging and grading). MATERIALS AND METHODS The expression of Ki-67, CD44H and vascular endothelial growth factor (VEGF) were assessed immunohistochemically in formalin-fixed, paraffin-embedded tissues from 48 RCCs, using a Ki-67 labelling index (LI), CD44 LI and level of VEGF expression, respectively. In addition all the pathological slides were reviewed retrospectively for the presence and absence of MVI. The prognostic value of all the variables assessed was then evaluated, and correlated with the usual prognostic variables and cancer-specific survival. RESULTS Univariate analysis of cancer-specific survival showed that tumour stage (P < 0.001), tumour size (P = 0.005), metastasis, MVI, Ki-67 LI, CD44H LI and VEGF expression (all P < 0.001) were predictors of tumour-related death. There was a statistical correlation between CD44H LI and each of Ki-67 LI (r = 0.61), expression level of VEGF (r = 0.72) and presence of MVI (r = 0.71). Independent predictors of cancer-specific survival in a multivariate analysis were: in all patients with RCC, the MVI (P = 0.003) and VEGF expression (P = 0.01); in those with no metastases, MVI (P = 0.01); in patients with no MVI, VEGF (P = 0.04); and in patients with MVI, Ki-67 LI (P = 0.003). No independent predictor was identified in patient with metastases. CONCLUSION This study suggests that cell proliferation, cell adhesion, the level of VEGF expression and the presence of MVI represent a complex tumour-host interaction that may favour the progression of RCC. Cell proliferation, CD44H and VEGF expression appear to be powerful markers for identifying patients with an adverse prognosis. [source]