Risk Of Understaging Research Articles

Primary Complete Transurethral Resection of Bladder Tumor Using Photodynamic Diagnosis for High-Risk Nonmuscle Invasive Bladder Cancer: Is a Restaging Photodynamic Transurethral Resection Really Necessary?

Objectives: To evaluate the risk of residual tumor and tumor upstaging during a second resection after primary complete transurethral resection of bladder tumor (TURBT) using photodynamic diagnosis (PDD) for high-risk nonmuscle invasive bladder cancer (NMIBC). Patients and Methods: From January 2014 to March 2020, a single-institutional study was conducted including consecutive patients with high-risk NMIBC (T1 and/or cis and/or high grade) who underwent a restaging transurethral resection (reTUR) within 12 weeks after a primary complete resection. Each TURBT was performed using blue light after intravesical instillation of hexaminolevulinate. The primary endpoint was detection of residual tumor at reTUR, proved with positive pathology report. Results: A total of 109 consecutive patients with high-risk NMIBC underwent reTUR after a primary complete blue light resection. Pathologic evaluation of the surgical specimens of the primary TURBT revealed stage T1 and high-grade tumors in 69 (68.3%) and 108 (99%) patients, respectively, and concomitant carcinoma in situ was found in 45 patients (41.3%). The median time to reTUR was 8 (6-10) weeks. Residual tumor was detected histopathologically in 64 of 109 patients (58.7%) at the second TURBT with PDD. In five of these patients (4.5%), initial T1 tumors were upstaged to T2 tumors. Conclusions: We examined a contemporary series of patients undergoing reTUR with PDD as management of high-risk NMIBC proven at the first blue light resection. We reported a 54.2% risk of disease persistence and a 4.5% risk of understaging in T1 tumors. These findings support that reTUR is still necessary after initial complete TURBT with PDD. Further studies are needed to assess the long-term oncologic outcomes of reTUR with PDD.

Interobserver, intraobserver, and interlaboratory variability in reporting pT4a colon cancer

Clinical significance of the pT4 category in colon cancer is increasing with several therapeutic implications. The aim of this study was to evaluate variability in diagnosing pT4a colon cancer. Twelve pathologists classified 66 preselected scanned Hematoxylin/Eosin-stained slides with tumor cells at a distance of 25–1500 μm (n = 22), 0–25 μm (n = 22), or on (n = 22) the peritoneal surface. Inter- and intraobserver variability were calculated using Kappa statistics. For interlaboratory variability, pathology reports of pT3 and pT4a colon cancer were extracted from the Dutch Pathology Registry between 2012 and 2015. The proportion of pT4a (pT4a/(pT3+pT4a)) was compared between 33 laboratories. Potential risk of understaging was assessed by determining the average number of blocks taken from pT3 and pT4a N0-2M0 tumors with metachronous peritoneal metastasis. Interobserver variability among 12 pathologists was 0.50 (95%CI 0.41–0.60; moderate agreement). Intraobserver variability (8 pathologists) was 0.71 (substantial agreement). A total of 7745 reports with pT3 or pT4aN0-2M0 colon cancer from 33 laboratories were included for interlaboratory analysis. Median percentage of pT4a was 15.5% (range 3.2–24.6%). After adjustment for case mix, 8 labs diagnosed pT4a significantly less or more frequently than the median lab. Metachronous peritoneal metastases were histologically verified in 170 of 6629 pT3 and in 129 of 1116 pT4a tumors, with a mean number of blocks of 4.03(SD 1.51) and 4.78 (SD 1.76) taken from the primary tumors, respectively (p < 0.001). A substantial variability in diagnosing pT4a colon cancer exists, both at pathologist and laboratory level. Diagnosis of pT4a stage appears to be challenging and there is a need for standardizing assessment of this pathological entity.

High cytoplasmic HuR expression is associated with advanced pT stage, high grade and increased microvessel density in urothelial bladder carcinoma.

HuR (human antigen R) protein is a RNA binding protein that stabilizes the mRNA and controls the translation of genes involved in cell proliferation, differentiation, and carcinogenesis. Overexpression of HuR was reported in a variety of cancers, however its clinical significance in urothelial bladder cancer (UBC) is still unknown. Our aim is to investigate the association between HuR expression and selected histopathological factors, such as tumor grade, pT stage, regional lymph nodes status and microvessel density (MVD). We studied expression of HuR protein in 119 patients with UBC in stages pTis and pTa-pT4 using immunohistochemistry (IHC). Tumor MVD was evaluated immunohistochemically using anti-CD31 antibody. We observed no association between nuclear HuR immunoreactivity and tumor grade, stage or MVD. We found a significant association between cytoplasmic HuR positivity and high tumor grade, pT stage and MVD (p<0,001). We also observed significantly higher MVD values in cases with positive cytoplasmic HuR expression (p<0,001). No association between HuR immunoreactivity and lymph nodes status was found. Our results may suggest that HuR is involved in the process of acquiring malignant histopathological features and ability to invade the muscularis propria by UBC cells. Considering frequent difficulties in diagnosing UBC in specimens obtained from transurethral tumor resection and the risk of understaging, cytoplasmic HuR expression would suggest an advanced disease and necessitate serial sectioning of the specimen in search of muscle invasion. Association between HuR expression and MVD could suggest HuR involvement in the process of angiogenesis in UBC.

Study on the Efficacy of Sentinel Lymph Node Identification by Radionuclide Method (Tc 99) Versus Combined Method (Radionuclide and Vital Stain) in the Staging of Breast Carcinoma

Abstract Introduction: Sentinel node biopsy is the gold standard for axillary assessment of patients with breast cancer without axillary metastases on clinical and radiological examination. Internationally accepted biopsy methods currently use a radioactive tracer (Te) or different variations of vital stain, or the combination of the two. Due to the high cost of technical and organizational difficulty related to the radioactive material, as well as the disadvantages of using the vital stain method, great effort is being made to find alternative solutions. The aim of this study was to determine the effectiveness of the exclusive use of vital stain versus the radioactive isotope, and the need to use the combined method. A second goal was the comparative analysis of the radioactive method and intraoperative assessment of suspicious (non-sentinel) lymph nodes. Materials and methods: This article is based on a prospective nonrandomized study conducted on 69 patients with early breast cancer in whom the combined method was used (injection of radionuclide and methylene blue vital stain). The comparatively monitored parameters were the following: the total and mean number of excised sentinel lymph nodes, the number of metastatic ganglia revealed by the 2 methods, and the risk of understaging in case only one technique was used. Results: We excised 153 sentinel nodes identified by the radioisotope method. Of these only 56 were stained with methylene blue (p &lt;0.0001). We could also identify a significantly higher number of metastatic nodes with the aid of the radioactive method (p = 0.0049). Most importantly, a significant number of patients (57.14%) who would have been declared node-negative using vital staining could only be properly staged using the radionuclide or the combined method. On microscopic examination of 35 non-sentinel lymph nodes, we found 3 lymph nodes with metastases, and in 1 case the metastases were found only in the non-sentinel lymph node. Conclusions: Given the risk of understaging, exclusive use of the vital stain method is not recommended, especially under the ASGO Z 00011 Protocol, since the more accurate determination of the number of metastatic sentinel lymph nodes in a patient influences the decision whether to perform lymphadenectomy or not. Using the combined method confers benefits only during the learning curve, in our database we found no stained nodes which were not radioactive. It is very important that the intraoperative stage uses the radioactive method and the intraoperative assessment of suspicious lymph nodes, because 35 non-sentinel lymph nodes were identified in our study, 3 of which had metastases, while in 1 case the metastases were in the non-sentinel lymph node.

Accurate Determination of the Pathological Stage with Gross Dissection Protocol for Radical Cystectomy

The current protocol for reporting urinary bladder cancer in radical cystectomies may exhibit limitations in the diagnostic accuracy, such as a risk of understaging, especially in cases with prostatic involvement. Difficulty can arise in the verification of stage pT0, and the assessment of surgical margins is suboptimal. We have developed a daily gross dissection protocol practice where radical cystectomies are totally embedded and evaluated histologically in whole-mount sections. We report here on the first 138 consecutive specimens from 2008 to the first quarter of 2012 inclusive. The incidence of the cancer stages was compared with data on 15,586 radical cystectomies from the literature. The differences were analyzed with the one-sample z-test (p < 0.05). The following emerged from and our series and the literature data: pT0 8.7 % and 6.1 %; pTa 0.7 % and 2.9 %; pTis 2.9 % and 6 %; pT1 15.2 % and 15.5 %; pT2 21 % and 23.3 %; pT3 34.8 % and 34.3 %; and pT4 16.7 % and 11 %, respectively. Our findings closely reflected the means of the published statistical data based on a large number of cases. The differences were due to the more detailed processing: the case numbers in groups from pTis to pT2 were comparatively low, while those in groups pT3 and pT4 were higher. The difference in group pT4 was significant (p = 0.0494). With this method, only those samples were regarded as pT0 in which the granulomatous area and the hemosiderin deposition indicative of the earlier intervention were observable and the entire preparation was tumor-free.

Abstract P6-02-01: Meta-Analysis of Ductal Carcinoma In Situ (DCIS) on Core Needle Biopsy — Underestimation and Predictors of Invasion

Abstract Background: A diagnosis of ductal carcinoma in situ (DCIS) on core needle biopsy (CNB) may represent an underestimate (or understaging) of invasive breast cancer (IBC). This is identified on excision histology in 4%-35% of CNB diagnoses of DCIS. It is of clinical significance as it may prevent informed discussion about management options for IBC and may mean that more than one surgical procedure is required. We systematically review the literature on CNB to report pooled estimates for underestimation of IBC following CNB diagnosis of DCIS and identify preoperative predictors of invasion. Methods: Studies were identified by searching MEDLINE and were evaluated against predetermined inclusion criteria: data were extracted independently by 2 authors. We calculated study-specific proportions for DCIS underestimates. Using meta-regression (random effects logistic models) we investigated the association between study-level preoperative variables and understaged IBC. Results: 47 studies met eligibility criteria reporting 6,213 cases of DCIS on CNB with excision histology as the reference standard. Table 1: Pooled underestimation rates for There were 1,482 underestimates (DCIS on CNB and IBC on excision); pooled estimate 25.9%(95% CI 22.2, 29.9). Preoperative variables associated with underestimation included ultrasound-guidance (vs stereotaxis), 14Gautomated (vs 11GVAB), high grade CNB lesion (vs nonhigh grade), size &amp;gt;20mm, BIRADS 4/5 (vs BIRADS3), mammographic mass (vs calc only) and palpability. Conclusion: Using available evidence we estimate that around 26% of CNB DCIS diagnoses represent understaged IBC. We identified preoperative variables associated with higher risk of understaging. This information can be used for preoperative discussion of management options, including possible sentinel node biopsy at the time of excision. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P6-02-01.

Does the Expression of Fascin-1 and Tumor Subclassification Help to Assess the Risk of Recurrence and Progression in T1 Urothelial Urinary Bladder Carcinoma?

Introduction: To evaluate the prognostic value of T1 subclassification and fascin-1 expression in T1 human urothelial cell carcinoma of the bladder. Materials and Methods: In a prospective study with 105 consecutive patients, T1 tumors were subclassified into 2 groups according to the depth of tumor invasion. The tunica muscularis mucosae was used as a landmark. The expression of fascin-1 was examined by using an anti-fascin-1 mouse monoclonal antibody and was evaluated semiquantitatively for both intensity and distribution. The patients were followed up for 27.3 ± 13.7 months. Results: The T1 tumor subclassification was feasible in 99 patients (94%). T1a tumor was detected in 77 patients (73%), T1b tumor in 22 patients (21%). An invasive tumor was found in 5 patients (4.8%) during the restaging transurethral resection of the bladder. The risk of understaging in patients with T1b tumor was 18%. There was not a significant difference in time to the recurrence in the T1a and the T1b group. The progression-free survival rates were significantly different between both groups (p = 0.0034). No correlation was found between fascin-1 positivity and the depth of tumor invasion. Fascin-1 positivity did not correlate with recurrence or the progression-free intervals. In the multivariate analysis, only the extent of lamina propria invasion was an independent predictor of the tumor progression. The fascin positivity was not an independent prognostic factor relating to the risk of recurrence or progression. Conclusion: The finding of T1b tumor was connected with a significantly higher risk of progression and understaging. The fascin-1 expression did not correlate with the depth of tumor invasion or with the tumor recurrence or progression.

The Role of the Surgeon and Transurethral Resection in the Treatment of Superficial Bladder Cancer

Non-muscle invasive bladder cancers are a heterogeneous group of cancers whose spectrum includes low grade Ta lesions and high-grade T1 lesions. Accurate staging and grading during initial evaluation and TUR ensures appropriate treatment and prevents the risk of understaging. TUR should be ideally performed under spinal anesthesia, with a continuous flow video resectoscope to maintain a stable bladder capacity, and a video monitor. The entire bladder must be visualized, with both 30- and 70-degree lenses, and all abnormal areas must be resected, with separate biopsies from each tumor's base. Repeat TUR is recommended for all high grade tumors and T1 tumors, especially if muscle was not present in the initial specimen. Immediate instillation of single dose chemotherapy agents following TUR is highly recommended to reduce the risk of tumor recurrences.

Lymph node recovery from colorectal tumor specimens: recommendation for a minimum number of lymph nodes to be examined.

Lymph node involvement is the most important prognostic factor for patients who have undergone radical surgery for colorectal carcinoma. An accurate examination of the surgical specimens is mandatory for the correct assessment of the lymph node status of the tumor. The risk of understaging is particularly high for patients with tumors classified as Dukes B (TNM stage II). The aim of this study was to determine if a specified minimum number of lymph nodes examined per surgical specimen could have any effect on the prognosis of patients who had undergone radical surgery for Dukes B colorectal cancer. Between 1988 and 1995 a total of 140 patients underwent radical resection of Dukes B colorectal cancer by the same surgeon (C.C.). The relation between clinicopathologic variables and survival was estimated using the Kaplan-Meier method. The Cox proportional hazard regression model was used to identify the variables that can independently influence survival. A median of 12 lymph nodes (range 3-38) was examined per tumor specimen. The 5-year survival rate of Dukes B patients who had had eight or fewer lymph nodes examined after surgery was 54.9%, whereas the survival rate for those who had had nine or more lymph nodes examined was 79.9% (p < 0.001). Cox regression analysis identified the number of lymph nodes as the only independent prognostic factor (p = 0.01). Seventy patients with one to four metastatic lymph nodes (Dukes C patients) who had been operated on during the same period were included in the survival analysis for comparison. The 5-year survival rate of the Dukes B patients with eight or fewer lymph nodes examined was similar to that of the 70 Dukes C patients (54.9% and 51.8%, respectively). Examination of eight or fewer lymph nodes in Dukes B colorectal patients may be considered a high risk factor for missing positive lymph nodes in the surgical specimens. Our results suggest that harvesting and examining a minimum of nine lymph nodes per surgical specimen may be sufficient for reliable staging of lymph node-negative tumors.

The value of endosonography in preoperative staging of rectal cancer.

Sixty-three patients with mobile rectal cancer were examined preoperatively with endorectal ultrasonography (EUS). The depth of infiltration and the presence of mesorectal lymph node metastases could be assessed in 53 patients. Doppler ultrasonography was performed in 16 cases with suspected lymph node enlargement in order to discriminate between lymph nodes and blood vessels. Tumour growth in the bowel wall was correctly estimated in 43 (81%) patients. The degree of spread was overestimated in five patients and underestimated in five. The evaluation of the mesorectal lymph node status was also accurate in 43 (81%) patients. Nine patients had one or several regional lymph node metastases, but the EUS revealed only some of the metastatic lymph nodes in each case. In the other 34, no lymph node metastases were found. In two patients the EUS was falsely positive since no lymph nodes could be demonstrated in the operative specimens. In eight patients the examination was falsely negative. EUS is considered to be an accurate method for preoperative assessment of tumour infiltration in the bowel wall as the risk of understaging was under 10%. Preoperative irradiation and surgery may be chosen based on the EUS-determined tumour extension into the rectal wall.