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Tumor Size (tumor + size)
Kinds of Tumor Size Selected AbstractsLongitudinal Diminution of Tumor Size for Basal Cell Carcinoma Suggests Shifting Referral Patterns for Mohs SurgeryDERMATOLOGIC SURGERY, Issue 1 2008ANDREW L. KAPLAN MD BACKGROUND The Mohs technique for removal of cutaneous malignancies offers tissue-sparing benefits compared with other treatment methods. With wider acceptance and availability of Mohs surgery, referral patterns may be shifting toward the treatment of smaller, lower-risk tumors. OBJECTIVE The objective was to examine whether referral patterns for basal cell carcinoma (BCC) at an academic Mohs surgery practice have shifted over recent years toward referral for smaller, lower risk tumors. METHODS A retrospective longitudinal comparison of tumor characteristics was performed for BCCs treated at our institution from a recent year (2004) and a past year (1996). Statistical analyses were used to identify differences in tumor size, distribution by anatomic site, and primary versus recurrent status. RESULTS Complete data were available for 603 BCCs treated in 1996 and 1,514 BCCs treated in 2004. A 24% decrease in preoperative tumor surface area was observed from 1996 (1.25 cm2) to 2004 (0.95 cm2). Tumors were twice as likely to be recurrent in 1996 (15.1%) than in 2004 (7.4%). There were no significant differences in the anatomic distribution of lesions in the years compared. CONCLUSIONS Findings at our institution suggest that in recent years, referral patterns have shifted toward a preference for Mohs surgery for the treatment of smaller, primary BCCs. This may be a result of increased awareness by the dermatologic and medical community of the numerous advantages of Mohs surgery and a greater appreciation of its tissue-sparing properties, which may result in less complex and more successful aesthetic reconstructions. [source] A Decision Tool for Predicting Sentinel Node Accuracy from Breast Tumor Size and GradeTHE BREAST JOURNAL, Issue 6 2007FRCS (Gen. Surg.), Nathan Coombs BSc Abstract:, The ability to predict axillary lymph node involvement in breast cancer patients in the preoperative setting is invaluable. This study provides a simple set of formulae to enable clinicians to make informed decisions in the management of screen-detected breast cancer. The tumor pathology reports were obtained of all 4,585 women identified between 1996 and 1999 in New South Wales (NSW) with T1 or T2 breast cancer by the statewide co-ordinated breast screening service (BreastScreen NSW). Equations predicting node positivity were calculated by linear regression analysis and, from published sentinel node false-negative rates, the probability of retrieval of a false-negative axillary lymph node by sentinel node biopsy was calculated for tumors of different size and grade. Node involvement was identified in 1,089 (23.8%) of women. A linear relationship for tumor size, grade, and nodal involvement was predicted by: frequency (%) = 1.5 × tumor size (mm) + 2 (or 6 or 10) for grade I (or II or III) tumors. Assuming a 7.5% false-negative rate, the probability of retrieving a false-negative sentinel node ranged from 0.8% for a patient with a 5 mm, grade I carcinoma to 6.0% for a 50 mm, grade III tumor. These simple formulae are easy to use in a clinical setting. The reference table enables breast surgeons to inform a patient about the absolute probability of false-negative sentinel biopsy rates for patients with screen-detected carcinomas when size can be estimated from preoperative imaging and when tumor grade is often available from preoperative core biopsy. Patients with large, T2 breast tumors may be best treated with axillary dissection rather than sentinel node biopsy alone due to the risk of under-staging the woman's disease and also the high probability of finding a positive sentinel node. [source] Ultrasound for Accurate Measurement of Invasive Breast Cancer Tumor SizeTHE BREAST JOURNAL, Issue 3 2006Ashraf Shoma FRCS Abstract: Accurate presurgical assessment of tumor size is important for choosing appropriate treatment, especially with the increasing use of neoadjuvant and minimally invasive therapy. Breast sonography is increasingly used by breast surgeons as a part of their basic clinical evaluation. We undertook this study to compare clinical evaluation, mammography, and breast sonography for evaluating breast tumor size. A prospective analysis of 124 consecutive patients with palpable breast cancer was performed. Tumor masses belonging to T1 and small T2 were selectively selected. All women had clinical, mammographic, and sonographic assessment of tumor size. Measurements were compared to the pathologic tumor size of the surgical specimen. Both mammographic and sonographic measurements tend to underestimate tumor size, while clinical assessment tends to overestimate it. Ultrasound was significantly more accurate in determining tumor size. The maximal tumor diameter measured was within 2 mm of the pathologic tumor size in 45.2% of cases measured by breast ultrasound, 28.2% of cases measured by mammography, and 14.5% of cases measured clinically. These data suggest that ultrasound is more accurate than clinical breast examination and mammography in assessing breast cancer size. Ultrasound assessment should be used by surgeons as an accurate adjunct to clinical examination in outpatient breast clinics. [source] Nerve of Origin, Tumor Size, Hearing Preservation, and Facial Nerve Outcomes in 359 Vestibular Schwannoma Resections at a Tertiary Care Academic CenterTHE LARYNGOSCOPE, Issue 12 2007Abraham Jacob MD Abstract Objective: To determine nerve of origin, tumor size, hearing preservation rates, and facial nerve outcomes in a retrospective cohort study of patients undergoing translabyrinthine (TL), middle cranial fossa (MCF), and retrosigmoid/suboccipital (SO) approaches to vestibular schwannomas (VS). Study Design: Retrospective. Methods: Chart review. Results: Patient charts from 231 TL, 70 MCF, 53 SO, and 5 combined TL/SO procedures for VS were evaluated in 356 patients. The inferior vestibular nerve (IVN) was the nerve of origin in 84 of 359 cases (23.3%), while the superior vestibular nerve (SVN) was the nerve of origin in 36 patients (10%). In 239 of 359 cases (66.6%), the nerve of origin was not identified. Forty patients undergoing hearing preservation surgery had hearing results and nerve of origin data available for review. Functional hearing (<50dB PTA and >50% speech discrimination) was preserved in 10 of 15 patients (75%) with SVN tumors, while only 7 of 25 patients (28%) with IVN tumors retained functional hearing. Facial nerve outcomes and nerve of origin were recorded simultaneously in 109 patients. Seventy-one of 74 patients (95%) patients with IVN tumors achieved a House-Brackmann (HB) grade I,III, while 35 of 35 patients (100%) with SVN tumors retained HB I,III facial function. Looking at tumor size versus hearing preservation, functional hearing was preserved in 22 of 49 patients (45%) with <1-cm tumors, and 4 of 20 patients (20%) with 1- to 1.5-cm tumors. For all cases with documented facial nerve function, HB I,III were achieved in 96% of SO, 94% of MCF, and 88% of TL procedures. Conclusions: Our retrospective data indicated that IVN tumors were twice as common as SVN tumors. The nerve of origin did not affect facial nerve outcomes but did impact hearing preservation rates. Patients with tumors <1 cm in size had the best chance for hearing preservation. Overall facial nerve preservation was excellent with >90% achieving HB 1 to 3 function at final follow-up. [source] Extensive Sampling Changes T-Staging of Infiltrating Lobular Carcinoma of Breast: A Comparative Study of Gross versus Microscopic Tumor SizesTHE BREAST JOURNAL, Issue 6 2006Neda A. Moatamed MD Abstract:, Infiltrating lobular carcinoma represents 7,10% of all invasive breast cancers. The greatest diameter of the tumors in the surgical specimens is required for an accurate T-staging. Tumors with dimension of zero cm, >0 to ,2 cm, >2 to ,5 cm, and >5 cm are staged as T0, T1, T2, and T3, respectively. A retrospective study on the specimens was performed on the specimens of 74 cases with infiltrating lobular carcinoma at the UCLA Medical Center from 2003 to 2005. The patients' ages ranged from 38 to 95 years. Specimens were from lumpectomy and mastectomy procedures on 36 and 38 patients, respectively. The specimens were divided in four groups according to the gross T-stages. Microscopic measurement of the tumors was carried out within each of the four groups for restaging purposes. Resizing of tumors was performed by marking the microscopic tumor extensions and compiling the measurements. In group 1, all 26 gross T0 tumors changed to T1 (69%), T2 (19%), and T3 (12%) after microscopic restaging. In group 2, 50% of the 26 gross T1 tumors became T2 (35%) and T3 (15%). In group 3, 9 (50%) of the T2 tumors changed to T3 microscopically. All 7 specimens (100%) in group 4 remained as T3. The results show that the gross measurements alone may underestimate 40,50% of the tumor T-stages. Therefore, the T-stages of the tumors with a gross size of 5 cm or less may change by microscopic resizing after an extensive sampling of the specimen. [source] Retrospective Review of Reconstructive Methods of Conchal Bowl Defects Following Mohs Micrographic SurgeryDERMATOLOGIC SURGERY, Issue 5 2001Nina Wines BSc Background. Mohs micrographic surgery has consistently been demonstrated to be the most effective method for excision of potentially aggressive lesions of the conchal bowl. A variety of techniques are employed to reconstruct the conchal bowl following surgery. Objective. To explore the type and frequency of reconstruction techniques used and the factors influencing the surgeons choice of reconstruction method. Method. Retrospective analysis of 272 patients with conchal bowl tumors. Results. Split thickness skin grafting was the preferred method of reconstruction. The histopathology of the lesions and the size of the post-Mohs defect did not influence the choice of technique, except for lesions less than 1 cm in which healing by secondary intention was favored. Conclusion. Tumor size, type, and aggressiveness did not influence repair technique choice. Surgeon preference was therefore the principle factor dictating method of reconstructive technique following Mohs micrographic surgery. [source] Dynamic T1-weighted monitoring of vascularization in human carcinoma heterotransplants by magnetic resonance imaging,INTERNATIONAL JOURNAL OF CANCER, Issue 1 2003Fabian Kiessling Abstract Studies on tumor angiogenesis and antiangiogenic therapies are commonly performed with tumor heterotransplants in nude mice. To monitor therapeutic effects, improved noninvasive analyses of functional data are required, in addition to the assessment of tumor volume and histology. Here, we report on sequential monitoring of vascularization of human squamous cell carcinomas growing as heterotransplants in nude mice using MRI. Using a custom-developed animal coil in a conventional whole-body 1.5 T MRI scanner, dynamic T1w sequences were recorded after i.v. injection of Gd-DTPA in tumors grown for 17, 21, 25, 29 and 33 days. Amplitude and the exchange rate constant (kep) were calculated according to a 2-compartment model, discriminating intravascular and interstitial spaces, and correlated with tumor size and histology. High-resolution imaging of small heterotransplants from 100 to 1,000 mm3 was achieved, clearly discriminating vital and necrotic areas. Preceding the development of necroses, which were hyperintense in T2w images and confirmed with histology, a local decrease of amplitude and kep values was observed. Significantly higher amplitudes were found in tumor periphery than in central parts, correlating well with the vascular pattern obtained by immunocytochemistry. Tumor size correlated negatively with amplitude, probably as a result of increasing necrotic areas, whereas the reason for the observed increase of kep value with tumor size remains unclear. These data demonstrate that dynamic MRI is an excellent method for noninvasive assessment of tumor vascularization in small animals using a clinical whole-body scanner with little technical modifications. This technique provides functional data characterizing essential features of tumor biology and is thus appropriate for monitoring antiangiogenic therapies. © 2002 Wiley-Liss, Inc. [source] Super giant basal cell carcinoma of the abdominal wall: still possible in the 21st centuryINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 7 2010Eelco De Bree MD Basal cell carcinoma (BCC) is very common and usually encountered when it is small in size. Giant BCC (i.e. greater than 5 cm in diameter) is quite rare and comprises 0.5 percent of all BCC. Extremely rarely, tumors larger than 20 cm have been reported. Herein, a case with an enormous, vegetating BCC of the abdominal wall, 30 x 20 cm in size, is described. This report demonstrates that such a case can still be observed in the civilized world of the 21st century, which remains profoundly astonishing. A literature survey was performed and revealed only 7 cases with such super giant BCC (i.e. larger than 20 cm in diameter). Generally, this tumor attains these enormous proportions due to neglect on the patient's part, and is usually located at sites covered by clothes. Treatment is mainly surgical and generally curative, resulting also in an improved quality of life. Tumor size of more than 10 cm in diameter is associated with increased risk for metastatic disease, severe morbidity and consequently impaired prognosis. [source] Renal cell carcinoma in dialysis patients: A single center experienceINTERNATIONAL JOURNAL OF UROLOGY, Issue 8 2006YASUYUKI KOJIMA Aim: Renal cell carcinoma (RCC) is a life-threatening complication of end-stage renal disease with an unclear pathogenesis. We evaluated RCC developing in patients undergoing dialysis. Methods: In 2624 patients undergoing hemodialysis or continuous ambulatory peritoneal dialysis at our hospital between July 1993 and March 2004, we performed annual screening for RCC using abdominal computed tomography and ultrasonography. Patients diagnosed with RCC underwent radical nephrectomy as well as clinical and pathologic evaluation. Results: RCC was detected in 44 patients (1.68%; 31 males and 13 females). The age of RCC patients was 55.5 ± 11.1 years. Dialysis duration before RCC diagnosis was 11.2 ± 7.2 years. Most RCC were early stage and low stage by TNM classification, 43 patients had N0M0 RCC, whereas one had N1M0. Tumor size was 2.9 ± 1.9 cm. The predominant histological type of RCC was common or conventional cell-type carcinoma (clear cell carcinoma and granular cell carcinoma). Of patients, 5(11.4%) had bilateral RCC, and satellite tumor lesions in RCC were detected in 13 (29.5%). In 36 patients (81.8%) RCC was accompanied by acquired cystic disease of the kidney. These patients had longer dialysis durations (P = 0.01) and smaller tumors (P = 0.048). RCC metastasized postoperatively in 4 patients (9.1%), while one (2.3%) died of cancer. Conclusions: Our dialysis patients showed a higher incidence of RCC than the general population. Prognosis was favorable because tumors were detected by screening when they were small. Therefore, periodical screening for RCC seems very important in dialysis patients. [source] Proliferative activity and genetic changes in adrenal cortical tumors examined by flow cytometry, fluorescence in situ hybridization and immunohistochemistryINTERNATIONAL JOURNAL OF UROLOGY, Issue 2 2005KOUSUKE TAKEHARA Abstract Background: To determine differences in biological features among different adrenal tumors, we investigated the DNA ploidy, numerical chromosomal aberration and proliferative activity in human adrenal cortical neoplasms. Methods: Our study included six adrenal cortical adenomas with Cushing syndrome, 12 adenomas with hyperaldosteronism, three non-functioning adenomas and three adrenal cortical carcinomas. Isolated nuclei from frozen samples were used for fluorescence in situ hybridization (FISH) analysis, and formalin-fixed, paraffin-embedded tissues from the same materials were analyzed using flow cytometry (FCM) for DNA ploidy. Sections from paraffin blocks were stained immunohistochemically with antibodies against Ki-67 and p53. For FISH analysis, we used an ,-centromeric enumeration probe for chromosome 17. Results: The mean Ki-67 labeling index (LI) of adrenal cortical carcinomas was markedly higher than that of adrenal cortical adenomas (209.4 vs 8.7). In functional adrenal cortical adenomas, the LI was significantly lower in adenomas with hyperaldosteronism than in those with Cushing syndrome (P = 0.004), although FCM results indicated that tetraploid patterns were more frequently observed in the former type. Tumor size was significantly smaller in adenomas with hyperaldosteronism than in those with Cushing syndrome (P = 0.004). Chromosome 17 showed disomy in all adrenal cortical adenomas, whereas chromosome 17 abnormalities were found in two of three adrenal cortical carcinomas. Only the latter two cases strongly expressed p53 protein. Conclusions: Our study characterized various biological features of benign and malignant adrenal cortical tumors. The use of a combination of markers might provide additional information to assist our understanding of the clinical behavior of an individual adrenal cortical tumor. [source] Localized lymphedema (elephantiasis): a case series and review of the literatureJOURNAL OF CUTANEOUS PATHOLOGY, Issue 1 2009Song Lu Background:, Lymphedema typically affects a whole limb. Rarely, lymphedema can present as a circumscribed plaque or an isolated skin tumor. Objective:, To describe the clinical and pathologic characteristics and etiologic factors of localized lymphedema. Methods:, Case,control study of skin biopsy and excision specimens histologically diagnosed with lymphedema and presenting as a localized skin tumor identified during a 4-year period. Results:, We identified 24 cases of localized lymphedema presenting as solitary large polyps (11), solid or papillomatous plaques (7), pendulous swellings (4), or tumors mimicking sarcoma (2). Patients were 18 females and 6 males with a mean age of 41 years (range 16,74). Anogenital involvement was most frequent (75%) , mostly vulva (58%), followed by eyelid (13%), thigh (8%) and breast (4%). Causative factors included injury due to trauma, surgery or childbirth (54%), chronic inflammatory disease (rosacea, Crohn's disease) (8%), and bacterial cellulitis (12%). Eighty-five percent of these patients were either overweight (50%) or obese (35%). Compared with a series of 80 patients with diffuse lymphedema, localized lymphedema patients were significantly younger (41 vs. 62 years old, p = 0.0001), had no history of cancer treatment (0% vs. 18%, p = 0.03), and had an injury to the affected site (54% vs. 6%, p = 0.0001). Histologically, all cases exhibited dermal edema, fibroplasia, dilated lymphatic vessels, uniformly distributed stromal cells and varying degrees of papillated epidermal hyperplasia, inflammatory infiltrates and hyperkeratosis. Tumor size significantly and positively correlated with history of cellulitis, obesity, dense inflammatory infiltrates containing abundant plasma cells, and lymphoid follicles (p < 0.05). A history of cellulitis, morbid obesity, lymphoid follicles and follicular cysts predicted recurrent or progressive swelling despite excision (p < 0.05). Conclusions:, Localized lymphedema should be considered in the etiology of skin tumors when assessing a polyp, plaque, swelling or mass showing dermal edema, fibrosis and dilated lymphatics on biopsy. A combination of lymph stasis promoting factors (trauma, obesity, infection and/or inflammatory disorders) produces localized elephantiasis. [source] Diffusion-weighted MRI for monitoring tumor response to photodynamic therapyJOURNAL OF MAGNETIC RESONANCE IMAGING, Issue 2 2010Hesheng Wang MS Abstract Purpose: To examine diffusion-weighted MRI (DW-MRI) for assessing the early tumor response to photodynamic therapy (PDT). Materials and Methods: Subcutaneous tumor xenografts of human prostate cancer cells (CWR22) were initiated in athymic nude mice. A second-generation photosensitizer, Pc 4, was delivered to each animal by a tail vein injection 48 h before laser illumination. A dedicated high-field (9.4 Tesla) small animal MR scanner was used to acquire diffusion-weighted MR images pre-PDT and 24 h after the treatment. DW-MRI and apparent diffusion coefficients (ADC) were analyzed for 24 treated and 5 control mice with photosensitizer only or laser light only. Tumor size, prostate specific antigen (PSA) level, and tumor histology were obtained at different time points to examine the treatment effect. Results: Treated mice showed significant tumor size shrinkage and decrease of PSA level within 7 days after the treatment. The average ADC of the 24 treated tumors increased 24 h after PDT (P < 0.001) comparing with pre-PDT. The average ADC was 0.511 ± 0.119 × 10,3 mm2/s pre-PDT and 0.754 ± 0.181 × 10,3 mm2/s 24 h after the PDT. There is no significant difference in ADC values pre-PDT and 24 h after PDT in the control tumors (P = 0.20). Conclusion: The change of tumor ADC values measured by DW-MRI may provide a noninvasive imaging marker for monitoring tumor response to Pc 4-PDT as early as 24 h. J. Magn. Reson. Imaging 2010;32:409,417. © 2010 Wiley-Liss, Inc. [source] Prognostic indicators in node-negative advanced gastric cancer patientsJOURNAL OF SURGICAL ONCOLOGY, Issue 7 2010Hiroaki Saito MD Abstract Background and Objectives Despite carrying better overall prognoses, some node-negative gastric cancer patients die from recurrent malignancies. Identifying factors associated with disease-specific survival in adequately staged node-negative gastric cancer is important, as these patients are presumably free of microscopic regional metastases and may derive significant benefit from existing or future adjuvant strategies. Methods To investigate significant prognostic indicators in node-negative advanced gastric cancer patients, we reviewed 777 advanced gastric cancer patients who had undergone curative gastrectomies. Results The 5-year survival rate of node-negative advanced gastric cancer patients is 84.9%, which is significantly better than that of patients with lymph node metastasis. Multivariate analysis indicated that tumor size, histology, and depth of invasion are independent prognostic factors. The 5-year survival rate of patients with larger tumors (,7,cm), poorly differentiated adenocarcinoma, and serosal invasion was 49.1%, which was significantly worse that of patients with fewer or none of these factors. Conclusions Tumor size, histology, and the presence of serosal invasion are strong indicators of poor prognosis in node-negative advanced gastric cancer patients. J. Surg. Oncol. 2010; 101:622,625. © 2010 Wiley-Liss, Inc. [source] Estimating breast cancer-specific and other-cause mortality in clinical trial and population-based cancer registry cohortsCANCER, Issue 22 2009James J. Dignam PhD Abstract BACKGROUND: To compute net cancer-specific survival rates using population data sources (eg, the National Cancer Institute's Surveillance, Epidemiology, and End Results [SEER] Program), 2 approaches primarily are used: relative survival (observed survival adjusted for life expectancy) and cause-specific survival based on death certificates. The authors of this report evaluated the performance of these estimates relative to a third approach based on detailed clinical follow-up history. METHODS: By using data from Cancer Cooperative Group clinical trials in breast cancer, the authors estimated 1) relative survival, 2) breast cancer-specific survival (BCSS) determined from death certificates, and 3) BCSS obtained by attributing cause according to clinical events after diagnosis, which, for this analysis was considered the benchmark "true" estimate. Noncancer life expectancy also was compared between trial participants, SEER registry patients, and the general population. RESULTS: Among trial patients, relative survival overestimated true BCSS in patients with lymph node-negative breast cancer; whereas, in patients with lymph node-positive breast cancer, the 2 estimates were similar. For higher risk patients (younger age, larger tumors), relative survival accurately estimated true BCSS. In lower risk patients, death certificate BCSS was more accurate than relative survival. Noncancer life expectancy was more favorable among trial participants than in the general population and among SEER patients. Tumor size at diagnosis, which is a potential surrogate for screening use, partially accounted for this difference. CONCLUSIONS: In the clinical trials, relative survival accurately estimated BCSS in patients who had higher risk disease despite more favorable other-cause mortality than the population at large. In patients with lower risk disease, the estimate using death certificate information was more accurate. For SEER data and other data sources where detailed postdiagnosis clinical history was unavailable, death certificate-based estimates of cause-specific survival may be a superior choice. Cancer 2009. © 2009 American Cancer Society. [source] Trends in the incidence and treatment of parathyroid cancer in the United StatesCANCER, Issue 9 2007Peter K. Lee MD Abstract BACKGROUND. Parathyroid cancer is a rare cause of hyperparathyroidism. The objectives of this study were to determine the patterns of disease, treatment trends, and outcomes among patients with parathyroid cancer by using a population-based data source. METHODS. Surveillance, Epidemiology, and End Results (SEER) cancer registry data were used to identify patients who were diagnosed with parathyroid cancer from 1988 through 2003. To assess whether the incidence rate, treatment, tumor size, and cancer stage changed over time, the Cochrane-Armitage trend test was used, and Cox proportional-hazards modeling was used to identify the factors associated with an improved overall survival rate. RESULTS. From 1988 through 2003, 224 patients with parathyroid cancer were reported in the SEER data. Over that 16-year study period, the incidence of parathyroid cancer increased by 60% (1988,1991, 3.58 per 10,000,000 population; 2000,2003, 5.73 per 10,000,000 population). Most patients (96%) underwent surgery (parathyroidectomy, 78.6% of patients; en bloc resection, 12.5% of patients; other, 4.9% of patients). The rate of surgical treatment increased significantly during the study period. The 10-year all-cause mortality rate was 33.2%, and the 10-year cancer-related mortality rate was 12.4%. Patient age (P < .0001), sex (P = .0106), the presence of distant metastases at diagnosis (P = .0004), and the year of diagnosis (P = .0287) were associated significantly with the overall survival rate. Tumor size, lymph node status, and type of surgery were not associated significantly with the overall survival rate. CONCLUSIONS. Although parathyroid cancer is rare, the incidence increased significantly in the United States from 1988 through 2003. Young age, female gender, recent year of diagnosis, and absence of distant metastases were associated significantly with an improved survival rate. Cancer 2007. © 2007 American Cancer Society. [source] Microsatellite distribution and indication for locoregional therapy in small hepatocellular carcinomaCANCER, Issue 2 2005Atsushi Sasaki M.D., Ph.D. Abstract BACKGROUND Intrahepatic disease recurrence is observed frequently after locoregional therapies for patients with hepatocellular carcinoma (HCC). However, the indication for locoregional therapy is still unclear. To clarify the indication for locoregional therapy for small HCC tumors, the authors measured the distance of microsatellites from the main tumor and analyzed the relation between this distance and clinicopathologic factors. METHODS The authors retrospectively analyzed 100 patients with small HCC tumors (, 5 cm in dimension) treated by curative hepatectomy. A microsatellite was defined as invasion into the portal vein or intrahepatic metastasis, and the distance from the main tumor to the most distant microsatellite was determined under light microscopy. The current study investigated the relation between microsatellite distance (0 mm if none present, , 5 mm, and > 5 mm) and clinicopathologic factors, as well as overall and disease-free survival rates after hepatectomy. RESULTS Of the 100 patients, 46 had microsatellites with a mean distance of 9.9 mm (median, 5.0 mm). Of the clinicopathologic factors investigated, tumor grade and preoperative ,-fetoprotein level significantly correlated with the presence of a microsatellite. Tumor size and distance to the microsatellite were significantly correlated. All but 1 tumor associated with a microsatellite distance > 5 mm was a high-grade tumor > 25 mm in greatest dimension. The overall survival rate of patients with a microsatellite distance of > 5 mm was lower than that of patients with a microsatellite distance < 5 mm. CONCLUSIONS Locoregional therapy, including limited resection and ablation therapies, was appropriate for patients with low-grade HCC tumors or with tumors < 25 mm in diameter. Cancer 2005. © 2004 American Cancer Society. [source] Increased mammography use and its impact on earlier breast cancer detection in Vermont, 1975,1999CANCER, Issue 8 2002Pamela M. Vacek Ph.D. Abstract BACKGROUND A trend toward earlier breast carcinoma detection in the United States has been attributed to screening mammography, although direct evidence linking this trend to the increased use of mammography in a general population is lacking. This study examined the effects of mammography on tumor size and axillary lymph node metastasis in Vermont over 25 years. METHODS Pathology and mammography data from 3499 Vermont women who were diagnosed with invasive breast carcinoma during 1975,1984, 1989,1990, and 1995,1999 were compared. Logistic regression analysis was used to estimate the effects of age, mammography use, and period on the odds of a tumor , 2 cm and the odds of negative lymph nodes. RESULTS The proportion of breast tumors that were detected by screening mammography increased from 2% during 1974,1984 to 36% during 1995,1999 (P < 0.001), and these tumors were more likely to measure , 2 cm than tumors that were detected by other methods. Among women age > 50 years, the odds ratio (OR) was 4.5, with a 95% confidence interval (95% CI) of 3.5,6.4. The effect was smaller in younger women (OR, 1.8; 95% CI, 1.1,3.0). Mammographic detection increased the odds of negative lymph nodes by a similar amount in both age groups, although women age > 50 years were more likely to have negative lymph nodes than younger women (OR, 1.3; 95% CI, 1.1,1.6). Tumor size and lymph node metastasis also were related to the number of mammograms and to the mammographic interval. CONCLUSIONS Most of the trend toward earlier detection in Vermont was due to mammography. Mammography had a lesser effect on tumor size among younger women, which may be related to less frequent screening, although its effect on lymph node metastasis was not age dependent. Women age < 50 years were more likely to have positive lymph nodes, independent of the method of detection or the frequency of mammography. Cancer 2002;94:2160,8. © 2002 American Cancer Society. DOI 10.1002/cncr.10459 [source] Fractional Cryosurgery for Skin CancerDERMATOLOGIC SURGERY, Issue 11 2009JOSE CARLOS ALMEIDA GONÇALVES MD BACKGROUND Cryosurgical treatment of facial skin cancers 10 mm or larger in diameter can originate retractile scars that may alter physiognomic features. OBJECTIVES To treat skin cancers 10 mm or larger in diameter on the face with a cryosurgical method that prevents retractile scars. Also, to clarify the differences between this method and Zacarian's segmental cryosurgery. METHODS AND MATERIALS Fractional cryosurgery is performed in stages. First, the center of the lesion is frozen, reducing its size, then this procedure is repeated as necessary until the tumor diameter is smaller than 10 mm, at which point the standard cryosurgical procedure is performed. Eighty-seven basal cell carcinomas (BCCs) and nine squamous cell carcinomas (SCCs) of the face (65 of which were orbital or periocular) measuring between 9 and 45 mm were treated. RESULTS The cure rate of BCCs was related to tumor size. All SCCs were cured without recurrence. Global mean follow-up was 4.5 years. CONCLUSION Fractional cryosurgery does not cause deformity, and the final scar has no relation to the mass of the original tumor but instead corresponds to the size of the lesion preceding the last cryosurgical procedure. [source] Longitudinal Diminution of Tumor Size for Basal Cell Carcinoma Suggests Shifting Referral Patterns for Mohs SurgeryDERMATOLOGIC SURGERY, Issue 1 2008ANDREW L. KAPLAN MD BACKGROUND The Mohs technique for removal of cutaneous malignancies offers tissue-sparing benefits compared with other treatment methods. With wider acceptance and availability of Mohs surgery, referral patterns may be shifting toward the treatment of smaller, lower-risk tumors. OBJECTIVE The objective was to examine whether referral patterns for basal cell carcinoma (BCC) at an academic Mohs surgery practice have shifted over recent years toward referral for smaller, lower risk tumors. METHODS A retrospective longitudinal comparison of tumor characteristics was performed for BCCs treated at our institution from a recent year (2004) and a past year (1996). Statistical analyses were used to identify differences in tumor size, distribution by anatomic site, and primary versus recurrent status. RESULTS Complete data were available for 603 BCCs treated in 1996 and 1,514 BCCs treated in 2004. A 24% decrease in preoperative tumor surface area was observed from 1996 (1.25 cm2) to 2004 (0.95 cm2). Tumors were twice as likely to be recurrent in 1996 (15.1%) than in 2004 (7.4%). There were no significant differences in the anatomic distribution of lesions in the years compared. CONCLUSIONS Findings at our institution suggest that in recent years, referral patterns have shifted toward a preference for Mohs surgery for the treatment of smaller, primary BCCs. This may be a result of increased awareness by the dermatologic and medical community of the numerous advantages of Mohs surgery and a greater appreciation of its tissue-sparing properties, which may result in less complex and more successful aesthetic reconstructions. [source] Evaluation of the American Joint Committee on Cancer Staging System for Cutaneous Squamous Cell Carcinoma and Proposal of a New Staging SystemDERMATOLOGIC SURGERY, Issue 11 2005Scott M. Dinehart MD Purpose. To identify and propose corrections for deficiencies in the American Joint Committee on Cancer (AJCC) system for staging cutaneous squamous cell carcinoma (CSCC). Materials and Methods. Prognostic factors for CSCC were identified by retrospective analysis of the published literature. Limitations and deficiencies in the current AJCC staging system for CSCC were then determined using these prognostic factors. Results. Size, histologic differentiation, location, previous treatment, depth of invasion, tumor thickness, histologic subtype, perineural spread, and scar etiology are the most powerful tumor prognostic indicators in patients with localized disease. The most important prognostic factors for patients with nodal metastases are the location, number, and size of the positive lymph nodes. Proposed changes for the T classification include increased stratification of tumor size, identification of patients with perineural invasion, and the addition of tumor thickness or depth of invasion. The N classification has been expanded to include the number and size of nodal metastases. Conclusion. The current AJCC staging system for carcinoma of the skin has deficiencies that limit its use for CSCC. The proposed TMN staging system for CSCC more accurately reflects the prognosis and natural history of CSCC. SCOTT M. DINEHART, MD, AND STEVEN PETERSON, MD, HAVE INDICATED NO SIGNIFICANT INTEREST WITH COMMERCIAL SUPPORTERS. [source] Intraoperative evaluation of sentinel lymph nodes in breast carcinoma by imprint cytology, frozen section and rapid immunohistochemistryDIAGNOSTIC CYTOPATHOLOGY, Issue 12 2009Sharma Upender M.D. Abstract Sentinel lymph nodes (SLN) isolated in 40 patients of breast carcinoma (stage T1/T2) were evaluated intraoperatively by imprint cytology and frozen section. Rapid immunohistochemistry (IHC) was done in cases where both imprint smears and frozen sections were negative for any metastatic tumor deposits. The results of these different techniques were compared with postoperative paraffin sections taken as "Gold Standard." Nottingham modification of Bloom Richardson scoring system was used for grading the tumors. Further, the correlation of the SLN status with tumor size, grade, and lymphovascular invasion was studied. The sensitivity, specificity, and overall accuracy of imprint cytology were 91.7, 100, and 95% respectively, and those of the frozen section were 95.8, 100, and 97.5% respectively. Examination of multiple serial sections improved the sensitivity and overall accuracy of frozen section. Results of intraoperative rapid IHC were equivalent to final paraffin sections. Histological grade and lymphovascular invasion were in direct correlation with SLN metastasis (P < 0.05). The risk of lymphovascular invasion increased from 22.2% in grade I tumors to 85.7% in grade III tumors. SLN biopsy is a reliable method to evaluate the status of the axillary lymph nodes. Imprint cytology can be used reliably where the facility of frozen section is not available. Diagn. Cytopathol. 2009. © 2009 Wiley-Liss, Inc. [source] Fine-needle aspiration cytology of Hürthle cell carcinoma of the thyroidDIAGNOSTIC CYTOPATHOLOGY, Issue 3 2008Howard Her-Juing Wu M.D. Abstract Specific criteria for the diagnosis of fine-needle aspiration (FNA) of Hürthle Cell Carcinoma (HCC) have rarely been discussed in the literature. A retrospective review of 35 FNA cases with the diagnosis of Hürthle cell lesion or Hürthle cell neoplasm was performed. In each case, there was a subsequent surgical excision. The FNA specimens were divided according to histologic diagnoses as HCC (12 cases), Hürthle cell adenoma (HCA) (14 cases), and benign nonneoplastic Hürthle cell lesions (BNHCL) (9 cases). Each case was examined using a semiquantitative scoring system for the following 11 features: presence or absence of colloid, lymphocytes, and transgressed blood vessels (each scored 0 or 1); the percentage of nuclear enlargement, small cell dysplasia, large cell dysplasia, nuclear crowding, and cellular dyshesion (each scored 0,3); and age, gender, and size of lesion. When diagnosed by FNA as either Hürthle cell neoplasm or Hürthle cell lesion, males were much more likely to have malignant tumors than females. Statistically significant cytologic features that favored malignant (HCC) over benign lesions (HCA and BNHCL) included small cell dysplasia, large cell dysplasia, nuclear crowding, and cellular dyshesion. The presence of colloid and lymphocytes favored a benign lesion. Nuclear enlargement and large tumor size are significantly more common in neoplasms than BNHCL. Diagn. Cytopathol. 2008;36:149,154. © 2008 Wiley-Liss, Inc. [source] Predictive factors for esophageal stenosis after endoscopic submucosal dissection for superficial esophageal cancerDISEASES OF THE ESOPHAGUS, Issue 7 2009H. Mizuta SUMMARY Endoscopic submucosal dissection (ESD) has been utilized as an alternative treatment to endoscopic mucosal resection for superficial esophageal cancer. We aimed to evaluate the complications associated with esophageal ESD and elucidate predictive factors for post-ESD stenosis. The study enrolled a total of 42 lesions of superficial esophageal cancer in 33 consecutive patients who underwent ESD in our department. We retrospectively reviewed ESD-associated complications and comparatively analyzed regional and technical factors between cases with and without post-ESD stenosis. The regional factors included location, endoscopic appearance, longitudinal and circumferential tumor sizes, depth of invasion, and lymphatic and vessel invasion. The technical factors included longitudinal and circumferential sizes of mucosal defects, muscle disclosure and cleavage, perforation, and en bloc resection. Esophageal stenosis was defined when a standard endoscope (9.8 mm in diameter) failed to pass through the stenosis. The results showed no cases of delayed bleeding, three cases of insidious perforation (7.1%), two cases of endoscopically confirmed perforation followed by mediastinitis (4.8%), and seven cases of esophageal stenosis (16.7%). Monovalent analysis indicated that the longitudinal and circumferential sizes of the tumor and mucosal defect were significant predictive factors for post-ESD stenosis (P < 0.005). Receiver operating characteristic analysis showed the highest sensitivity and specificity for a circumferential mucosal defect size of more than 71% (100 and 97.1%, respectively), followed by a circumferential tumor size of more than 59% (85.7 and 97.1%, respectively). It is of note that the success rate of en bloc resection was 95.2%, and balloon dilatation was effective for clinical symptoms in all seven patients with post-ESD stenosis. In conclusion, the most frequent complication with ESD was esophageal stenosis, for which the sizes of the tumor and mucosal defect were significant predictive factors. Although ESD enables large en bloc resection of esophageal cancer, practically, in cases with a lesion more than half of the circumference, great care must be taken because of the high risk of post-ESD stenosis. [source] Thoracoscopic enucleation of esophageal leiomyoma: a retrospective study on 40 casesDISEASES OF THE ESOPHAGUS, Issue 3 2009G. Jiang SUMMARY Esophageal leiomyoma is the most common benign esophageal tumor. Thoracoscopic enucleation is currently a preferred approach to most of these lesions. We present our experiences of enucleation of these tumors using thoracoscopic approach. A retrospective review of 40 patients who underwent enucleation of esophageal leiomyoma from 1997 to 2007 in our institute was conducted. Presenting symptoms, operative approach, tumor size, tumor shape, outcomes, and indication for this approach were analyzed. Forty patients were identified. Postoperative histopathology confirmed the leiomyoma in all patients. The thoracoscopic enucleation was completed in 34 cases, and the operation was converted to open procedure in six cases. Reasons for conversion included too small tumors to be visualized in two cases, thoracic cavity adhesion in one case, and the too large tumors in three cases. The median operating time was 70 min (50 to 210 min). Mean tumor size was 3.7 cm (0.5,10 cm). There were no major postoperative complications. Symptoms especially dysphasia were relieved postoperatively. Short- and long-term follow-up was satisfactory with none of the patients having tumor recurrences or other problems. Thoracoscopic enucleation of esophageal leiomyoma is technically safe and effective. It is currently the best choice for management of esophageal leiomyoma 1 to 5 cm in diameter. It can also be tried on a tumor larger than 5 cm, although the possibility of conversion to thoracotomy increases along with tumor growing and surrounding the esophagus. [source] Surgical treatment of esophageal leiomyoma located near or at the esophagogastric junction via a thoracoscopic approachDISEASES OF THE ESOPHAGUS, Issue 2 2009Z. G. Li SUMMARY Esophageal leiomyoma can be enucleated safely and effectively by minimally invasive surgery. The laparoscopic approach has been a conventional option for this kind of tumor located near or at the esophagogastric (EG) junction. The aims of this study were to evaluate the surgical outcome of thoracoscopic resection of leiomyoma at the EG junction, and discuss factors affecting the incidence of postoperative gastroesophageal reflux. Fourteen patients who underwent thoracoscopic resection of esophageal leiomyoma located near or at the EG junction (<4 cm above the esophageal hiatus) from January 2002 to August 2007 were reviewed retrospectively. Tumor characteristics, surgical methods, and postoperative outcomes were evaluated. A left approach of video-assisted thoracoscopy was used in 13 patients; a right approach was used for the other patient, whose multiple tumors were located in the EG junction and mid-esophagus. Postoperative recovery was uneventful in all patients, with no mucosa leakage or other significant complications. Mean tumor size was 3.2 cm (1.2,6.0 cm). Of the 14 patients, two had serpiginous leiomyoma, two had multiple tumors, and the others had solitary tumors. Mean postoperative stay in hospital was 7 days (4,11 days). Postoperative dysphagia was not reported, although gastroesophageal reflux was noted in one patient. Thoracoscopic resection of esophageal leiomyomas near or at the EG junction is feasible, with a low prevalence of postoperative gastroesophageal reflux. [source] Impact of hemoglobin level on survival in definitive chemoradiotherapy for T4/M1 lymph node esophageal cancerDISEASES OF THE ESOPHAGUS, Issue 3 2008S. Zenda SUMMARY., We retrospectively investigated the impact of the pre-chemoradiotherapy hemoglobin level (pre-CRT Hb level) for T4 and/or M1 lymph node (LYM) squamous cell carcinoma of the esophagus. Chemotherapy consisted of protracted infusion with 5-fluorouracil (5-FU) at 400 mg/m2/day on days 1,5 and 8,12, combined with cisplatin at 40 mg/m2/day on days 1 and 8, repeated twice at a 5-week interval. Concurrent radiation therapy was started on day 1 and delivered at 2 Gy/day for five days a week for a total radiation dose of 60 Gy, with a two-week break after a cumulative dose of 30 Gy. Several factors considered to be related with treatment outcome were evaluated by univariate and multivariate analysis. A total of 48 patients with T4/M1 LYM (lymphocyte) esophageal cancer treated with chemoradiotherapy (CRT) between September 2002 and April 2005 were enrolled. The complete response rate to this regimen was 44% and median survival time was 13.6 months, with a median follow-up period of 26.8 months. Median pre-CRT Hb level was 13.5 (10.4,15.3) g/dL. The CR rate in patients with a pre-CRT Hb level of 13 g/dL or less was only 24% but it was 60% in those with a level that was more than 13 g/dL (P=0.01). As for survival, anovarevealed that a pre-CRT Hb of 13 g/dL or less was a significant prognostic factor with a hazard ratio of 0.45 (95% confidence interval [CI]); 0.21,0.97, P=0.04), while on manova, including performance status, tumor size, TNM stage and pre-CRT Hb level, a pre-CRT Hb level of 13 g/dL or less was the only significant prognostic factor, with a hazard ratio of 0.35 (95% CI; 0.13,0.90, P=0.03). In conclusion, the pre-CRT Hb level may be an important determinant of outcome in patients with T4/M1 LYM squamous cell carcinoma of the esophagus. [source] Tumor budding as a useful prognostic marker in esophageal squamous cell carcinomaDISEASES OF THE ESOPHAGUS, Issue 4 2004M. S. Roh SUMMARY, We examined the prognostic significance of tumor budding in patients with esophageal squamous cell carcinoma, particularly in comparison to other routine pathological findings. Fifty-six cases who underwent an esophagectomy were reviewed. We defined tumor budding as an isolated single cancer cell or a cluster composed of fewer than five cancer cells and divided these into two grades; low-grade (< 5 budding foci) and high-grade (, 5 budding foci) within a microscopic field of ×200. There were 22 (39.3%) and 34 (60.7%) cases with low- and high-grade budding, respectively. There were significant differences in the patients with low- and high-grade budding in relation to tumor size, pT stage, lymphovascular invasion, perineural invasion, circumferential resection margin involvement, and AJCC stage (P < 0.05). The 3-year survival rates of the patients with low- and high-grade budding were 72.3% and 30.7%, respectively (P = 0.04). We propose that tumor budding may be a pathological marker suggesting high malignancy potential and decreased postoperative survival in patients with esophageal squamous cell carcinoma. [source] Evaluation of mutant frequencies of chemically induced tumors and normal tissues in ,/cII transgenic miceENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 1 2005Jon C. Mirsalis Abstract Genomic instability has been implicated as an important component in tumor progression. Evaluation of mutant frequencies (MFs) in tumors of transgenic mice containing nontranscribed marker genes should be useful for quantitating mutation rates in tumors as the physiologically inactive transgene provides neither a positive nor a negative selective pressure on the tumor. We have conducted long-term carcinogenicity studies in ,/cII transgenic B6C3F1 mice using a variety of genotoxic and nongenotoxic test agents and have evaluated the mutant frequencies in both tumors and normal tissues from these animals. Mice were administered diethylnitrosamine (DEN) as three intraperitoneal injections of 15 mg/kg; phenobarbital (PB) or oxazepam (OXP) provided ad libitum at 0.1% or 0.25% in the diet, respectively; DEN initiation plus PB in the diet; or urethane (UTH) provided ad libitum at 0.2% in the drinking water. Normal tissues and tumors were isolated at various times over a 2-year period and half of each tissue/tumor was evaluated histopathologically and the other half was evaluated for MF in the cII transgene. Approximately 20 mutants from each of 166 individual tissues (tumor and nontumor) were sequenced to determine whether increases in MF represented unique mutations or were due to clonal expansion. UTH produced significant increases in MF in normal liver and lung. DEN either with or without PB promotion produced significant increases in MF in liver and correction of MF for clonality produced little change in the overall MF in these groups. PB produced a twofold increase in liver MF over controls after 27 weeks of treatment, but a similar increase was not observed with longer dosing times; at later time points, the MF in the PB groups was lower than that of the control group, suggesting that PB is not producing direct DNA damage in the liver. OXP failed to produce an increase in MF over controls, even after 78 weeks of treatment. Selected cases of genomic instability were observed in tumors from all treatments except OXP, with individual liver tumors showing very high MF values even after clonal correction. One rare and interesting finding was noted in a single mouse treated with UTH, where a mammary metastasis had an MF approximately 10-fold greater than the parent tumor, with 75% of the mutations independent, providing strong evidence of genomic instability. There was no clear correlation between tumor phenotype and MF except that pulmonary adenomas generally had higher MFs than normal lung in both genotoxic and nongenotoxic treatment groups. Likewise, there was no correlation between tumor size and MF after correction for clonality. The results presented here demonstrate that individual tumors can show significant genomic instability, with very significant increases in MF that are not attributed to clonal expansion of a single mutant cell. Environ. Mol. Mutagen., 2005. © 2004 Wiley-Liss, Inc. [source] Glutathione S-transferase P1 and alpha gene variants; role in susceptibility and tumor size development of oral cancerHEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 8 2010Mu-Kuan Chen MD Abstract Background. The aim of this study was to estimate the relationship of glutathione S-transferases (GST)P1, GSTA1, GSTM1, and GSTT1 gene polymorphisms to oral cancer risk. Methods. Polymerase chain reaction,restriction fragment length polymorphism (PCR-RFLP) was used to measure these 4 gene polymorphisms in 274 controls and 164 oral cancer patients. Results. Individuals with at least 1 varied G allele of GSTP1 had a 1.53-fold risk (95% confidence interval [CI] = 1.01,2.31) of developing oral cancer compared with patients with wild-type A/A homozygotes. Oral cancer patients with at least 1 varied T allele of GSTA1 gene had a 0.42-fold risk (95% CI = 0.18,0.95) of having a tumor size >2 cm compared with patients with C/C homozygotes. Conclusions. The varied G allele of GSTP1 may be considered as a factor contributing to increased susceptibility, whereas the T allele of GSTA1 could be a protective factor for tumor size progression in Taiwanese with oral cancer. © 2009 Wiley Periodicals, Inc. Head Neck, 2010 [source] The value of frozen section in intraoperative surgical management of thyroid follicular carcinoma,HEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 7 2003Danijel Do, en MD Abstract Background. Preoperative and intraoperative diagnosis of follicular carcinoma (FC), resulting in one-stage surgical treatment of follicular thyroid tumors, is an important issue in thyroid surgery. Methods. In the 10-year period there were 4158 operations performed on thyroid gland. There were 1559 patients with follicular tumors, 70 (4.4%) of them having FC. We analyzed the groups of patients with FC determined on frozen section (FS) and permanent section (PS) according to duration of clinical symptoms, ultrasound (US) examination, tumor size, patient gender and age, intensity of invasion, localization, and multiple or solitary occurrence of tumor. Results. FC was diagnosed in 39 (55.7%) patients on frozen section (FS). Among the encapsulated (minimal invasion) carcinomas, the FS was accurate in 19 of 33 (57.6%) FC and in 5 of 15 (27.8%) Hürthle cell carcinomas (HCC); among extensively invasive carcinoma in 11 of 14 (78.6%) FC and in 4 of 5 (80.0%) HCC. FC was significantly more common in men (p < .001) and in the right lobe (p < .05). We did not find statistically significant differences concerning duration of symptoms, US examination, tumor size, patient age, and multiple or solitary occurrence of the tumor between the patients with FC diagnosed on FS and the patients with FC diagnosed on PS. Conclusions. The intraoperative diagnosis of FC is difficult. Although the percentage of false-negative results was relatively high (44.3%), there were no false-positive results. This means that the second operation was avoided in 55.7% of the patients, and no unnecessary thyroidectomies were performed. FS biopsy is an important method in surgery of follicular tumors. Improved technical support and the ability to analyze a greater number of slides will increase the accuracy of the method. © 2003 Wiley Periodicals, Inc. Head Neck 25: 521,528, 2003 [source] | ||||||||||||||||||||||||||||||||||||||||