-
[show abstract]
[hide abstract]
ABSTRACT: To evaluate the feasibility of performing sentinel node detection in patients with renal cell carcinoma (RCC).
An open series of 13 arbitrarily selected patients with T1b-T3b RCC scheduled for radical nephrectomy at a single Tertiary Academic Centre were examined with different modalities of sentinel node detection. Preoperative ultrasonography-guided injection of radioactive isotope, lymphoscintigram and single photon emission computed tomography/computed tomography, followed by intraoperative gamma-probe detection and Patent Blue detection, as well as postoperative scintigram of the main specimen were the planned interventions. These investigations were performed in conjunction with intended open radical nephrectomy.
In 10 of the 13 patients sentinel node detection was achieved with 32 sentinel nodes displayed. Radio-guided surgery using an intraoperative gamma-probe resulted in the highest realtive detection rate with detection of sentinel nodes in nine patients. In total, nine metastatic sentinel nodes were detected in three patients. One patient, preoperatively staged as N+, was restaged after sentinel node detection and histopathology as pN0.
Sentinel node detection in renal tumours is feasible although evaluation of different modes of detection needs further refinement and standardization. All nodes preoperatively detected by routine computed tomography as suspicious metastatic lesions were confirmed as sentinel nodes, including two nodes considered as metastatic by preoperative routine imaging but ultimately staged as non-metastatic sentinel nodes.
BJU International 08/2011; 109(8):1134-9. · 2.84 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Despite optimal surgical treatment and modern adjuvant therapies, 50% of patients diagnosed with colorectal cancer die within 5 years. Immunotherapy offers an appealing complement to traditional chemotherapy, with possible long-term protection against tumor recurrences through immunological memory. We have conducted a pilot study of a novel adoptive immunotherapy, using autologous, in vitro expanded lymphocytes isolated from the tumor-draining sentinel lymph node.
Sentinel nodes were recovered from 16 patients with disseminated or locally advanced, high-risk colorectal cancer. Single-cell suspensions of sentinel-node-acquired lymphocytes were clonally expanded in vitro in the presence of autologous tumor extract and returned as a transfusion. Patients were followed with clinical and radiological evaluations. Long-term survival was compared with traditionally treated controls.
Sentinel-node-acquired CD4(+) Th1-lymphocytes could be clonally expanded in vitro and safely administered to all 16 patients without side-effects. In four out of nine stage IV patients, complete tumor regression occurred. Median survival time in the stage IV patients (n = 9) was 2.6 years, as compared with 0.8 years in conventionally treated controls. A dose-dependent effect with regards to reduced tumor burden and long-term survival was observed.
Sentinel-node-based adoptive immunotherapy is feasible; the method has shown no apparent side-effects and appears to convey therapeutic antitumor effects. Further studies are justified to determine its efficacy and precise role in the treatment of colorectal cancer.
Annals of Surgical Oncology 07/2010; 17(7):1747-57. · 4.17 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Expected 2-yr survival for patients with urothelial urinary bladder cancer (UBC) with lymph node involvement (pN2) is 20%, regardless of standard neoadjuvant/adjuvant oncologic treatment. Tumor-reactive lymphocytes are present in sentinel nodes (SNs) draining human bladder cancer and display immunologic function on restimulation in vitro. Metinel nodes (MNs) drain secondarily from metastatic tumors and also possess tumor-reactive lymphocytes, which might be a source for adoptive T-cell immunotherapy.
To determine if MN detection and subsequent expansion of autologous T-helper cells with subsequent reinfusion was feasible and safe to perform in patients with metastatic UBC.
In an open trial, the first 12 included patients are described. Patients were prospectively selected from a single tertiary academic center and had metastatic UBC. All 12 patients were preoperatively staged as T2-T4b N1-2 and/or M0-M1 or MX.
MNs were excised in conjunction with intended cystectomy. T lymphocytes were extracted with enhancement and expansion of tumor specific T-helper cells, followed by reinfusion of expanded T cells.
All patients were preoperatively staged with transurethral resection of the bladder and routine computed tomography scan. Intended detection of MNs was performed intraoperatively with intended cystectomy. Harvested T cells were evaluated and cell cultures were established. Assessment of reinfusion of expanded, autologous, tumor-specific T-helper cells to six of the patients was performed, focusing on adverse effects.
In six patients, it was feasible to administer the treatment. Reinfusion of these T cells was performed without any major adverse effects. In six other patients, we encountered technical failures.
A novel adoptive immunotherapy based on T cells from tumor-draining lymph nodes is feasible in advanced UBC. Infusion of expanded, autologous, tumor-specific T-helper cells might be a future treatment option in metastasized UBC. Long-term overall survival remains to be determined.
European urology 09/2009; 58(1):105-11. · 7.67 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: In spite of newly developed chemothera-peutic regiments, surgery, radiotherapy and the introduction of anti-angiogenic drugs
the prognosis in disseminated colorectal cancer is poor. Recent investigations correlating expression markers with clinical
outcome in patients with colon ancer indicate that tumor infiltrating lymphocytes are prognostically favourable, suggesting
an important role for immune cells in the defense against cancer. Hitherto undertaken adoptive immunotherapy programs have
focused on using tumor infiltrating lymphocytes with some success, but these cells are frequently suppressed by immune escape
mechanisms induced by the tumor. However, recent advances in surgery and basic immunology have allowed the identification
of the natural immune response, harbored in tumor draining lymph nodes, sentinel nodes. The sentinel node offers a promising
new source, rich in tumor recognizing T lymphocytes that seem to be useful for immunotherapy. This chapter discusses relative
immunology and rationale for using sentinel node acquired lymphocytes for adaptive immunotherapy of colon cancer.
12/2008: pages 291-312;
-
[show abstract]
[hide abstract]
ABSTRACT: Mesenteric lymph nodes may play a crucial role in the pathogenesis of human inflammatory bowel disease. We have used the sentinel node technique to analyze mesenteric lymph nodes draining inflammatory lesions sentinel nodes and corresponding site of inflamed bowel in patients with ulcerative colitis or Crohn's disease.
Thirty-two patients undergoing surgical treatment of inflammatory bowel disease were included. Sentinel nodes were identified intraoperatively. The T cells were harvested from the mesenteric lymph nodes and characterized by flow cytometry.
The distribution of CD4CD62L (homing-marked) and CD4CD69 (activated) T cells was studied in mesenteric lymph nodes draining inflammation, nodes draining normal intestine, blood, and mucosa. The turnover of T cells was markedly increased in the lymph nodes connected to inflammatory segments. The immunologic activity of the sentinel lymph nodes correlated with the degree of intestinal inflammation.
Mesenteric sentinel nodes provide important information about locoregional immunology and pathogenesis in inflammatory bowel disease.
European journal of gastroenterology & hepatology 11/2008; 20(10):985-8. · 1.66 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The execution of appropriate gene expression patterns during immune responses is of eminent importance where CpG methylation has emerged as an essential mechanism for gene silencing. We have charted the methylation status of regulatory elements in the human IFNG gene encoding the signature cytokine of the Th1 response. Surprisingly, human naive CD4(+) T lymphocytes displayed hypermethylation at the IFNG promoter region, which is in sharp contrast to the completely demethylated status of this region in mice. Th1 differentiation induced demethylation of the IFNG promoter and the upstream conserved nucleotide sequence 1 enhancer region, whereas Th2-differentiated lymphocytes remained hypermethylated. Furthermore, CD19(+) B lymphocytes displayed hypomethylation at the IFNG promoter region with a similar pattern to Th1 effector cells. When investigating the methylation status among tumor-infiltrating CD4(+) T lymphocytes from patients with colon cancer, we found that tumor-infiltrating lymphocytes cells are inappropriately hypermethylated, and thus not confined to the Th1 lineage. In contrast, CD4(+) T cells from the tumor draining lymph node were significantly more demethylated than tumor-infiltrating lymphocytes. We conclude that there are obvious interspecies differences in the methylation status of the IFNG gene in naive CD4(+) T lymphocytes, where Th1 commitment in human lymphocytes involves demethylation before IFNG expression. Finally, investigations of tumor-infiltrating lymphocytes and CD4(+) cells from tumor draining lymph node demonstrate methylation of regulatory regions within key effector genes as an epigenetic mechanism of tumor-induced immunosuppression.
The Journal of Immunology 09/2008; 181(4):2878-86. · 5.79 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: We previously identified tumor-reactive lymphocytes in the first lymph nodes that drain the primary tumor. In this study, we performed lymphatic mapping to investigate the possibility of finding the first lymph nodes that drain metastases, and of learning whether these lymph nodes contained tumor-reactive lymphocytes suitable for adoptive immunotherapy.
Nineteen patients were studied. The primary tumor site was colorectal cancer in seven patients, malignant melanoma in four, ovarian cancer and breast cancer in two, and one each with pancreatic cancer, cholangiocarcinoma, leiomyosarcoma, and squamous cellular cancer of the tongue. By injection of Patent blue dye or radioactive tracers around the metastases, we identified draining lymph nodes from liver metastases (n = 9), intra-abdominal local recurrences (n = 3), and regional lymph node metastases (n = 7). In six patients, a preoperative lymphoscintigraphy was performed.
We located the first draining lymph node or nodes from metastases or local recurrences; we named them "metinel nodes." Lymphocytes from the metinel nodes proliferated, showed clonal expansion, and produced interferon gamma (via in vitro expansions on stimulation with tumor homogenate) and interleukins, all of which demonstrate the characteristics of tumor-reactive lymphocytes. Eight of the nineteen patients received immunotherapy on the basis of tumor-reactive T cells derived from the metinel nodes.
We demonstrate that it is possible to locate the first lymph nodes draining subcutaneous, lymphatic, and visceral metastases, the so-called metinel nodes. Metinel node-derived lymphocytes may be used to treat disseminated solid cancer, and clinical trials should evaluate the effect of such treatment.
Annals of Surgical Oncology 06/2008; 15(5):1454-63. · 4.17 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: In colon cancer the presence of metastases in the regional lymph nodes is an important prognostic factor. Currently, examination is based on histological and immunohistochemical evaluations of lymph node sections. However, these methods are time-consuming, labour intensive and micro-metastases might be missed. The sentinel node technique may be used to identify the direct tumour draining lymph node. In this study the possible use of flow cytometry for detection of sentinel node metastases in patients with colon cancer has been investigated. Peripheral blood mononuclear cells (PBMC) with the addition of DLD-1 colon cancer cells were stained intracellularly for cytokeratin 20 (CK20), and for the cell surface markers epithelial cell adhesion molecule (EpCAM) and carbohydrate antigen 19-9 (CA19-9). CK20 positive colon cancer cells were reliably detected with as few as 0.037% events. However, PBMCs from both colon cancer patients and from healthy individuals contained CK20 positive cells. Staining for EpCAM resulted in an almost complete recovery of tumour cells, and as few as 0.037% added cells were detected. Low intra-assay variability was determined for EpCAM (CV 8.8) and CA19-9 (CV 9.7) stainings. The results from staining for CK20 or for EpCAM and CA19-9 concorded, but the degree to which respective antigens were expressed varied. The use of flow cytometry for detection of metastatic colon cancer cells was verified in fourteen sentinel nodes specimens from patients with colon cancer. Herein we have explored the potential of flow cytometry to become a fast, sensitive and reliable method for detection of lymphatic metastases in patients with colon cancer using direct fluorophore-conjugated antibodies against multiple surface antigens. The method seems feasible and further testing is warranted.
Journal of Immunological Methods 06/2008; 334(1-2):122-33. · 2.20 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Naturally occurring thymus derived regulatory T cells (Tregs) are central in the maintenance of self-tolerance. The transcription factor FOXP3 is crucial for the suppressive activity of Tregs and is considered the most specific marker for this population. However, human non regulatory T cells upregulate FOXP3 transiently upon activation which calls for other means to identify the Treg population. Since epigenetic mechanisms are involved in the establishment of stable gene expression patterns during cell differentiation, we hypothesized that the methylation profile of the FOXP3 promoter would allow the distinction of truly committed Tregs.
Human CD4(+)CD25(hi) Tregs displayed a demethylated FOXP3 promoter (1.4%+/-0.95% SEM methylated) in contrast to CD4(+)CD25(lo) T cells which were partially methylated (27.9%+/-7.1%). Furthermore, stimulated CD4(+)CD25(lo) T cells transiently expressed FOXP3 but remained partially methylated, suggesting promoter methylation as a mechanism for regulation of stable FOXP3 expression and Treg commitment. In addition, transient FOXP3 expressing cells exhibited suppressive abilities that correlate to the methylation status of the FOXP3 promoter. As an alternative to bisulphite sequencing, we present a restriction enzyme based screening method for the identification of committed Tregs and apply this method to evaluate the effect of various culturing conditions. We show that a partial demethylation occurs in long-term cultures after activation, whereas the addition of TGF-beta and/or IL-10 does not induce any additional change in methylation level.
The unique FOXP3 promoter methylation profile in Tregs suggests that a demethylated pattern is a prerequisite for stable FOXP3 expression and suppressive phenotype. Presently, FOXP3 is used to identify Tregs in several human diseases and there are future implications for adoptive Treg transfer in immunotherapy. In these settings there is a need to distinguish true Tregs from transiently FOXP3(+) activated T cells. The screening method we present allows this distinction and enables the identification of cells suitable for in vitro expansions and clinical use.
PLoS ONE 02/2008; 3(2):e1612. · 4.09 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To study the effect of oral steroids upon clinical response and rectal mucosa secretion of eosinophil cationic protein (ECP), myeloperoxidase (MPO), basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF) and albumin in patients with collagenous colitis (CC).
A segmental perfusion technique was used to collect perfusates from rectum of CC patients once before and twice (one and four weeks) after the start of steroid treatment. Clinical data was monitored and ECP, MPO, bFGF, VEGF and albumin concentrations were analyzed by immunochemical methods in perfusates and in serum.
Steroids reduced the number of bowel movements by more than five times within one week and all patients reported improved subjective well-being at wk 1 and 4. At the same time, the median concentrations of ECP, bFGF, VEGF and albumin in rectal perfusates decreased significantly. MPO values were above the detection limit in only 3 patients before treatment and in none during treatment. VEGF, bFGF, ECP and albumin concentrations correlated with each other with the exception of ECP and albumin. A decrease of serum ECP and VEGF concentrations was also seen even if the overtime reduction was not significant.
Oral steroid treatment in CC patients induced a simultaneous reduction of bowel movements and rectal release of ECP, bFGF, VEGF and albumin, suggesting that these polypeptides and increased mucosal permeability are important components of the pathophysiology in collagenous colitis.
World Journal of Gastroenterology 12/2006; 12(43):7012-8. · 2.47 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To explore the feasibility of performing lymphoscintigraphy combined with computed tomography (CT) for preoperative detection of sentinel lymph nodes in patients with invasive bladder cancer.
Six consecutive patients scheduled for radical cystectomy underwent lymphoscintigraphy after transurethral injection of Albures-technetium 99m in the detrusor muscle peritumourally both with planar imaging and with single-photon emission computed tomography/CT (SPECT/CT). CT for anatomic fusion was performed directly after the SPECT/CT and both investigations were combined to a fused image. Radical cystectomy started with extended lymphadenectomy and intraoperative detection of sentinel nodes with both Geiger probe and dye marker. The conventional planar lymphoscintigraphies and the fused SPECT/CT were compared with each other and with the outcome of intraoperative sentinel node detection and final histopathologic analyses.
The method allowed anatomically detailed preoperative visualisation of 21 sentinel nodes in five of the six patients, whereas planar pictures only visualised two sentinel nodes in two of six patients. Two patients had lymph node metastases and in the other four the nodes were negative. The combined method visualised all metastatic sentinel nodes, whereas planar lymphoscintigraphy detected only one of six node metastases.
The combination of lymphoscintigraphy with CT enhanced preoperative anatomic localisation of sentinel nodes in bladder cancer and aided in the identification of sentinel nodes during surgery. The yield of detected sentinel nodes, both metastatic and nonmetastatic, was markedly increased using the combined method compared to conventional planar lymphoscintigraphy.
European Urology 08/2006; 50(1):83-91. · 8.49 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The lymphatic drainage from a tumour is received in the sentinel node where the immune system encounters tumour derived antigens. We investigated anti-tumoural lymphocyte function in sentinel nodes from patients with urinary bladder cancer.
In 14 patients undergoing cystectomy due to bladder cancer, radioactive tracer and blue dye were used to identify the sentinel node. Cell suspensions from the tumour, sentinel- and non-sentinel nodes and peripheral blood were analyzed by flow cytometry with antibodies against lymphocyte surface antigens and against the tumour cell marker cytokeratin-20. Reactivity against autologous tumour extract and the mitogen Concanavalin A was tested in proliferation assays with 3H-Thymidine incorporation. Lymphocytes were put in long-term culture with IL-2 and autologous tumour extract.
Sentinel nodes were detected in 12 of the 14 patients. Antigen dependent proliferation in response to autologous tumour extract was detected in 6 patients, in 5 cases in sentinel nodes, in the remaining case in a non-sentinel node. Proliferation against Concanavalin A was vigorous in lymph nodes from all patients, whereas tumour infiltrating lymphocytes were unresponsive. Lymphocytes from sentinel nodes could be expanded in vitro.
Tumour reactive lymphocytes are present in sentinel nodes draining human bladder cancers. These cells display immunologic function upon restimulation in vitro, and provide a promising source for expansion and subsequent adoptive T cell immunotherapy.
European Urology 02/2006; 49(1):59-70. · 8.49 Impact Factor
-
The Journal of Urology 08/2004; 172(1):386; author reply 386. · 3.75 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Patients with collagenous colitis have watery diarrhea and histopathologically thickened collagen layer with discrete signs of mucosal inflammation. Vascular endothelial growth factor (VEGF) is a potent angiogenic, mitogenic, permeability, and fibrosis enhancing peptide and it was studied by segmental perfusion and immunohistochemistry in patients and controls. The concentrations of VEGF were significantly increased in perfusates from both the descending colon and the rectum in patients compared to controls but this difference was not found in serum. Immunohistochemical staining showed expression of VEGF within colon epithelial cells, inflammatory cells, and fibroblasts in the lamina propria. The intensity of staining in the surface epithelium was not different between patients and controls but in the lamina propria the intensity was significantly higher among controls. Patients with collagenous colitis have increased colorectal mucosal secretion of VEGF, which may lead to albumin leakage and promote fibrosis with deposition of collagen.
Digestive Diseases and Sciences 02/2004; 49(1):109-15. · 2.12 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Collagenous colitis (CC), a condition of unknown ethiology and pathophysiology, is characterized by watery diarrhea and increased amounts of collagen in the colonic mucosa. Basic fibroblast growth factor (bFGF) is a potent multifunctional growth factor that stimulates proliferation and differentiation of fibroblasts that was recently detected in high intraluminal concentrations in patients with ulcerative colitis. In this study we examined the secretion and expression of bFGF in the colorectal mucosa of patients with CC.
Ten CC patients and 10 control patients underwent colonoscope-based segmental perfusion of the descending colon and rectum. The concentrations of bFGF in perfusate and serum were determined by immunochemical methods, and the expression of bFGF was analyzed immunohistochemically in biopsy samples from colonic mucosa.
The median concentrations of bFGF in perfusates from the descending colon and rectum were increased 4-fold in CC patients compared with control patients. The median concentration of bFGF in serum was not significantly different in patients and controls. Immunohistochemical staining of bFGF was located in the colorectal epithelial cells and in exsudate on the luminal side of these cells. In the lamina propria, inflammatory cells and fibroblasts contained bFGF. There were no differences in the intensity of bFGF staining in surface epithelium or lamina propria between patients and controls.
Local investigation of the colorectal mucosa seems to be crucial when studying the pathophysiology of CC. Increased colorectal mucosal secretion of bFGF in patients with CC may promote differentiation of fibroblasts and thereby lead to increased subepithelial collagen deposition.
The American Journal of Gastroenterology 10/2003; 98(9):2011-7. · 7.28 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: We characterized early metastatic progression of bladder carcinoma from the primary tumor, separated in the central part and invasive front, to the first lymphatic metastasis.
Included in this study were 8 patients undergoing sentinel lymph node detection for invasive bladder cancer, of whom 4 had metastasis in the sentinel lymph node and 4 were randomly chosen without metastases. After microdissection p53 genomic structure and immunohistochemical expression of p53, pRB, Ki67 and E-cadherin were analyzed. Microvessel density and apoptosis were also assessed.
In 5 patients there were p53 gene mutations in the primary tumor, while 3 had the wild-type gene. The genotypes were identical in the central part and invasive front. All sentinel lymph node metastases harbored p53 mutations, in contrast to all nonmetastatic sentinel lymph nodes. Two patients had the same mutation as the primary tumor and 1 had an additional mutation. In a patient with a wild-type gene in each compartment of the primary tumor a mutation appeared in the corresponding sentinel lymph node metastasis. There was poor concordance of p53 mutation with protein status. The expression of p53, pRB, Ki67, E-cadherin, and the evaluation of apoptosis and angiogenesis showed in most cases only slight variations in tumor compartments and the sentinel lymph node.
In this study invasive bladder carcinoma involved monoclonal proliferations with a mainly homogenous biomarker profile. The first metastases in sentinel lymph nodes had a similar molecular profile but in half of the cases signs of clonal evolution appeared.
The Journal of Urology 12/2002; 168(5):2240-4. · 3.75 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The local release of human neutrophil lipocalin, considered to be highly specific for neutrophil granulocyte activation, and interleukin-8 and tumor necrosis factor-alpha were studied in 11 patients with distal ulcerative colitis and proctitis before and during treatment with steroid enemas. A rectal perfusion technique for sampling and specific immunoassays for analysis were used. In responders (N = 8) the concentrations of all proteins decreased during the study. There was a close correlation between human neutrophil lipocalin concentrations and treatment response. Tumor necrosis factor-alpha showed an initial decline in concentrations irrespective of treatment outcome and preceded the decline of human neutrophil lipocalin and interleukin-8. We conclude that decreased neutrophil degranulation is correlated with treatment outcome. Furthermore, an important role of tumor necrosis factor-alpha in the process of stimulating neutrophil activation and degranulation in ulcerative colitis is suggested.
Digestive Diseases and Sciences 10/2002; 47(9):2064-9. · 2.12 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Functional results after elective colonic resection in patients with diverticular disease have seldom been studied.
Seventy-five consecutive patients were reviewed and sent a questionnaire about abdominal symptoms and functional results. Possible associations between patients' characteristics and postoperative complications or functional outcome were analyzed.
Major complications including anastomotic leakage, bleeding, and bowel obstruction occurred in 10 patients (13%). Six patients (8%) had recurrent diverticulitis. No significant associations were found between clinical characteristics and postoperative complications or recurrent disease. Fifty patients classified their final result as excellent or good. Functional symptoms or symptoms suggestive of irritable bowel syndrome before the operation predicted a less successful result (P <0.05).
Elective surgery in patients with diverticular disease was hampered by postoperative complications but resulted in most cases in good functional outcome and a low rate of recurrent disease. Those with functional bowel symptoms before surgery had significantly worse results.
The American Journal of Surgery 02/2002; 183(1):7-11. · 2.78 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: We studied second primary cancer among 25,947 patients diagnosed with squamous cell carcinoma of the skin (SCC) in Sweden between 1958 and 1992. In total, 5,706 patients developed a second primary cancer at any site, compared with an expected number of 2,651 [standardized incidence ratio (SIR) = 2.15; 95% confidence interval (CI) = 2.10–2.21]. Men below 60 years of age at diagnosis of SCC had higher SIR (2.5; CI = 2.2–2.8) with the highest risk during the first year of follow-up (SIR = 9.2; CI = 6.9–12.2). If second primary SCC was excluded, the SIR was reduced to 1.30 (CI = 1.25–1.34); the relationships by sex, age and time since diagnosis remained similar. For skin cancer, the SIR for second SCC was markedly elevated (SIR = 15.6) and the risk of malignant melanoma was elevated 3-fold. Significantly increased risks were found for most second cancers in squamous cell epithelium: lip (SIR = 5.2), respiratory organs (SIR = 1.7), esophagus (SIR = 1.5), cervix uteri (SIR = 2.2), and vulva including vagina (SIR = 2.3). There was a generally increased risk of almost 2-fold for second cancer in hematopoietic or lymphoproliferative tissues. Slightly increased rates (SIR = 1.0–1.5) were seen for second tumors in digestive tissues. Finally, a high SIR (SIR = 5.5) was observed for second primary cancer in salivary glands. In conclusion, patients with SCC are at increased risk to develop new primary cancer, especially in skin, squamous cell epithelial and tobacco-related tissues. Common risk factors among the tumor types might explain our findings, however, an intrinsic susceptibility among SCC patients to develop cancer is also possible. Int. J. Cancer 80:511–515, 1999. © 1999 Wiley-Liss, Inc.
International Journal of Cancer 02/1999; 80(4):511 - 515. · 5.44 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: This study investigates the incidence trends of urinary bladdercancer in Sweden from 1960 through 1993 (a total of 46,211 cases).Age-standardized incidence rates increased among men from 14.6 per 10 5 in1960 to 33.5 in 1993 and among women from4.8 to 8.8, corresponding to anaverage annual increase of 2.4 percent (95 percent confidence interval [CI])= 2.0-2.7 percent) and 1.1 percent (CI = 0.9-1.4 percent), respectively. Thelargest increase occurred in the oldest age-groups. The proportion ofpatients with transitional cell carcinoma increased in menfrom66.0 percent in1960-64 to 93.6 percent in 1990-93 and in women from 61.0 percent to 89.4percent. The proportion of patients with papillomas decreased, whereas thosewith adenocarcinoma and squamous cell carcinoma were stable. Regressionmodeling (based on the period 1960-89) showed a strong linear effect due toeither period and/or cohort. Among men, additional non-linear effects by bothperiod and cohort were obtained. T he cohort effects were more important.Cohort data on having smoked daily showed considerable similarities with theestimated cohort-effects. Our findings suggest that the increase of tobaccosmoking in successive generations can explain the increase in incidence ratesof bladder cancer in Sweden, whereas improved diagnostic activities andregistration are less likely to explain fully the changes in incidence rates.
Cancer Causes and Control 06/1997; 8(4):560-567. · 2.88 Impact Factor
