Pathologic Stage Classification Research Articles

Dos and don’ts in designing a computerized oral and lip squamous cell cancer registry

BackgroundIn the last ten years, many countries have started to develop constructive systems for registering common diseases and cancers. In this research, we intended to determine and identify the minimum data set (MDS) required for the design of the oral and lip squamous cell cancer registration system in Iran.Methods and materialAt first, primary information elements related to disease registries were extracted using scientific papers published in reliable databases. After reviewing the books, related main guidelines, and 42 valid articles, the initial draft of a researcher-made questionnaire was compiled. To validate the questionnaire, two focus group meetings were held with 29 expert panel members. The final version of this questionnaire was prepared by extracting different questions and categories and receiving numerous pieces of feedback from specialists. Lastly, a final survey was conducted by the experts who were present at the previous stage.ResultsOut of 29 experts participating in the study, 17 (58.62%) were men and 12 (40.37%) were women. The age range of experts varies from 34 to 58 years. One hundred-fourteen items, which are divided into ten main parts, were considered the main information elements of the registry design. The main minimum data sets have pertained to the demographic and clinical information of the patient, information related to the consumed drugs, initial diagnostic evaluations of the patient, biopsy, tumor staging at the time of diagnosis, clinical characteristics of the tumor, surgery, histopathological characteristics of the tumor, pathologic stage classification, radiotherapy details, follow-up information, and disease registry capabilities. The distinctive characteristics of the oral and lip squamous cell cancer registry systems, such as the title of the disease registration programme, the population being studied, the geographic extent of the registration, its primary goals, the definition of the condition, the technique of diagnosis, and the kind of registration, are all included in a model.ConclusionThe benefits of designing and implementing disease registries can include timely access to medical records, registration of information related to patient care and follow-up of patients, the existence of standard forms and the existence of standard information elements, and the existence of an integrated information system at the country level.

Surgical and functional outcomes of Retzius-sparing robotic-assisted radical prostatectomy versus conventional robotic-assisted radical prostatectomy in patients with biopsy-confirmed prostate cancer. Are outcomes worth it? Systematic review and meta-analysis.

Radical prostatectomy is the standard of care for prostate cancer. Retzius-sparing robotic-assisted radical prostatectomy (RS-RARP) is being widely adopted due to positive functional outcomes compared to conventional robotic-assisted radical prostatectomy (c-RARP). Concerns regarding potency, oncological outcomes, and learning curve are still a matter of debate. Following Preferred Instrument for Systematic Reviews and Meta-Analysis guidelines and PROSPERO registration CRD42023398724, a systematic review was performed in February 2023 on RS-RARP compared to conventional c-RARP. Outcomes of interest were continence recovery, potency, positive surgical margins (PSM), biochemical recurrence (BCR), estimated blood loss (EBL), length of stay (LOS), operation time and complications. Data were analyzed using R version 4.2.2. A total of 17 studies were included, totaling 2751 patients, out of which 1221 underwent RS-RARP and 1530 underwent c-RARP. Continence was analyzed using two definitions: zero pad and one safety pad. Cumulative analysis showed with both definitions statistical difference in terms of continence recovery at 1 month (0 pad odds ratio [OR] = 4.57; 95% confidence interval [CI] = [1.32-15.77]; Safety pad OR = 13.19; 95% CI = [8.92-19.49]), as well as at 3 months (0 pad OR, 2.93; 95% CI = [1.57-5.46]; Safety pad OR = 5.31; 95% CI = [1.33-21.13]). Continence recovery at 12 months was higher in the one safety pad group after RS-RARP (OR = 4.37; 95% CI = [1.97-9.73]). The meta-analysis revealed that overall PSM rates without pathologic stage classification were not different following RS-RARP (OR = 1.13; 95% CI = [0.96-1.33]. Analysis according to the tumor stage revealed PSM rates in pT2 and pT3 tumors are not different following RS-RARP compared to c-RARP (OR = 1.46; 95% CI = [0.84-2.55]) and (OR = 1.41; 95% CI = [0.93-2.13]), respectively. No difference in potency at 12 months (OR = 0.98; 95% CI = [0.69-1.41], BCR at 12 months (OR = 0.99; 95% CI = [0.46-2.16]), EBL (standardized mean difference [SMD] = -0.01; 95% CI = [-0.31 to 0.29]), LOS (SMD = -0.01; 95% CI = [-0.48 to 0.45]), operation time (SMD = -0.14; 95% CI = [-0.41 to 0.12]) or complications (OR = 0.9; 95% CI = [0.62-1.29]) were observed. Our analysis suggests that RS-RARP is safe and feasible. Faster continence recovery rate is seen after RS-RARP. Potency outcomes appear to be similar. PSM rates are not different following RS-RARP regardless of pathologic stage. Further quality studies are needed to confirm these findings.

MON-436 Cribriform-morular Variant of Papillary Thyroid Carcinoma: A Case Report

Background:Cribriform - morular variant is a rare variant of papillary cancer with 1–2 % prevalence. There are no established guidelines to screen for thyroid cancer in patients with APC gene mutations and FAP. We present a case of a young female with APC gene mutation and thyroid cancer.Case:Female, 25 years-old, without anemia, underwent colonoscopy at age 22 and multiple polyps were seen. One polyp showed intramucosal carcinoma with high-grade dysplasia. She was diagnosed with FAP. She was found to have APC gene mutation on genetic analysis. No family history of FAP was reported.Chest and abdominal CT showed multiple thyroid nodules.Thyroid ultrasound showed 3 nodules. The largest is in the mid R lobe, measuring 1 cm, and is isoechoic to hypoechoic, containing some small central cystic areas. The nodules in the left lobe measure 0.6 and 0.7 cm.FNA of the right thyroid nodule showed follicular neoplasm. Afirma was suspicious.She underwent total thyroidectomy.Pathology report showed multifocal tumor in both right (0.8 cm) and left lobe (0.5 cm). Histologic type was Papillary carcinoma, cribriform - morular variant. All surgical margins were negative. No angio-lymphatic invasion or extra thyroidal extension was identified.Pathologic stage classification was m pT1a pN0 pM0.Patient did not receive RAI ablation.Patient doing well and no further recurrence of thyroid cancer is noted.Discussion:Patients with FAP have a greatly increased risk for colorectal cancer and also have an elevated risk for other cancers including thyroid cancer (1%-2% compared to 1% in general population). According to ACG guidelines of 2015, annual thyroid screening by ultrasound should be recommended to individuals affected with FAP. Additionally, thyroid cancer found in unscreened patients with FAP was more advanced as compared to patients screened for cancer requiring less aggressive approaches. On ultrasonography, most nodules had benign-looking features (well-defined, hypoechoic, oval to round shapes without calcification), but some nodules had capsular invasion and larger height: width shape. In preoperative FNA, they were diagnosed as CMV-PTC/PTC but could also present as follicular neoplasm or PTC-follicular variant. Compared to conventional PTC, CMV-PTC had a lower frequency of lymph node metastases at presentation (12%) and distant metastases (3%) as well as lower recurrence rates (8.5%) and patient mortality rates (2%). Physical exam and clinical history is not sufficient to screen for cancer.In patients with APC gene mutations and FAP, there should be high suspicion for diagnosing thyroid cancer as the nodules are usually benign looking and small in size. As noted in the case, nodules were found incidentally, and tumor size was small with benign looking nodules. Additionally, screening should be focused more on young females below the age of 35 because of the high prevalence of cancer.

The 8th edition American Joint Committee on gastric cancer pathological staging classification performs well in a population with high proportion of locally advanced disease

BackgroundThe 8th edition of AJCC gastric cancer pathological staging system (AJCC8) derived from the IGCA database needs an external validated in cohorts with higher proportion of advanced disease. Patients and methodsA total of 5386 gastric cancer patients treated at Chang Gung Memorial Hospital (CGMH) and Veteran General Hospital in Taipei (TVGH) were enrolled. Clinicopathological data of the IGCA series and the CGMH/TVGH cohort were compared. Cumulative survival curves of the CGMH/TVGH cohort as stratified by the AJCC7 and the AJCC8 were compared. Lymph node ratio (LNR) was analyzed in patients with N3b disease. ResultsPatients in the CGMH/TVGH cohort were older and had more advanced tumor stage (stage III, 49% versus 26%, p < 0.001) than those in the IGCA cohort. The median survival of stages IIIA, IIIB, and IIIC as defined by the AJCC 8 were 49, 27 and 15 months, respectively, with narrower 95% confidence intervals, in comparison with 62, 30 and 18 months, respectively, as defined by the AJCC7. The AJCC8 exhibited better homogeneity within stages and discriminatory ability between stages, compared to the AJCC7. Six hundred and four patients with N3b disease were stratified by LNR into three subgroups, and their median survival were 31, 17, and 11 months, respectively (p < 0.001). LNR further appeared as a powerful outcome predictor of N3b disease (HR, 3.1). ConclusionThe AJCC8 performs well in patients with high proportion of advanced gastric cancer. We recommend that LNR is a supplementary prognostic indicator for N3b disease.

Improved Fat Clearance Techniques for the Examination of Breast Cancer Lymph Nodes

Introduction: The isolation of lymph nodes less than 4.0 mm in diameter from the fatty tissue of surgical breast cancer specimens through the traditional method of tactile perception is difficult, time consuming and failed the identification of smaller lymph nodes. The reported numbers of lymph nodes detected through this technique vary widely in the literature demonstrating its inappropriateness. The use of fat clearance techniques however may contribute to the isolation of additional nodes, allowing for appropriate pathological staging of the disease. Objective: To evaluate the impact of the use of fat clearance machinery and solutions in the dissection and identification of lymph nodes from axillary dissections of patients with breast cancer. Materials and methods: Fat clearance techniques (cooker, electric spiral, modified Koren clearing solution and formaldehyde-acetic alcohol solution) were applied to 100 breast cancer axillary dissections from males and females with no age restriction over a period of two years (2009-2011). Results: Through the use of fat clearance methods, additional 174 metastases in 564 lymph nodes were found, more than the classical method, from which 449 metastases in 1426 lymph nodes were identified. There was no statistical difference between the fat clearance methods; however the cooker method demonstrated greater efficiency than the modified Koren clearing solution method. Conclusion: The fat clearance methods described here have various advantages over the classical method. These methods are viable, rapid, practical, inexpensive and do not alter the quality of histological analysis or immunohistochemical reactions. The findings show that examination of a minimum of 20 isolated lymph nodes is necessary for optimal identification and diagnosis of lymph node metastases. The main outcome from this study were the immediate benefits generated by adopting new technical procedures resulting in a change in pathological staging classification in 14% of the patients.

Correlation of elevated ALCAM shedding with patient outcome in colorectal cancer.

46 Background: ALCAM (Activated Leukocyte Cell Adhesion Molecule) is a cell-cell adhesion protein that has been highlighted as a putative biomarker for the progression of many cancers, including colorectal cancer (CRC). Current prognosis for CRC patients predominantly rely on pathologic staging classification. Although TNM staging successfully stratifies high-risk patients, there is significant variability in the rate of disease progression within each stage. Previous studies evaluating ALCAM as a biomarker for predicting colorectal cancer patient survival have published conflicting and inconclusive results. The aim of this present study was to investigate the prognostic value of ALCAM shedding, quantified using a dual stain that detects both the extracellular and the intracellular domains in formalin-fixed tissue, in colorectal patients. Methods: A novel dual-immunohistological detection of ALCAM shedding was performed on tissue microarrays constructed from 75 colorectal primary tumors and 9 healthy control specimens. Tissue was assessed by CellProfiler image analysis to obtain quantitative estimates of ALCAM shedding, defined as the detection of the intracellular domain the absence of the extracellular domain of ALCAM. Two tailed p values ≤ 0.05 were considered to be statistically significant. Results: ALCAM shedding was elevated in 33/79 (41.8%) of tissue from CRC patients compared to healthy controls (p=0.0239). Univariate analysis of CRC patients, stages I-IV, revealed a statistical significance correlating high ALCAM shedding with worse overall survival (p=0.0401). Moreover, ALCAM shedding is a predictor of overall survival (p=0.432) and more notably, disease-specific survival in stage II patients (p=0.0098). Conclusions: Detection of ALCAM shedding allows for stratification of patients according to their risk for poor long-term outcome. Considering that ALCAM is altered in a number of malignancies, the clinical correlation of ALCAM shedding to patient outcome is likely to extend beyond CRC to other cancers.

Staging of breast cancer in the neoadjuvant setting.

The use of neoadjuvant chemotherapy has become more prevalent in the treatment of breast cancer patients. The finding of a pathologic complete response to neoadjuvant chemotherapy (no evidence of residual invasive cancer in the breast and lymph nodes at the time of surgical resection) has been shown to correlate with improved survival. The current version of the American Joint Committee on Cancer (AJCC) staging for breast cancer has a pretreatment clinical stage designation that is determined by clinical and radiographic examination of the patient and a postoperative pathologic stage classification based on the findings in the breast and regional lymph nodes removed at surgery. Pathologic staging has not been validated for patients receiving neoadjuvant chemotherapy; thus, prognosis is determined for these patients based on the pretreatment clinical stage. We hypothesized that clinical and pathologic staging variables could be combined with biological tumor markers to provide a novel means of determining prognosis for patients treated with neoadjuvant chemotherapy. Two scoring systems, based on summing binary indicators for clinical and pathologic substages, negative estrogen receptor status, and grade 3 tumor pathology, were devised to predict 5-year patient outcomes. These scoring systems facilitated separation of the study population into more refined subgroups by outcome than the current AJCC staging system for breast cancer, and provide a novel means for evaluating prognosis after neoadjuvant therapy.

Nodal Stage Classification for Breast Carcinoma: Improving Interobserver Reproducibility Through Standardized Histologic Criteria and Image-Based Training

Reliable pathologic stage classification of axillary lymph nodes is an important determinant of prognosis and therapeutic decision making for patients with invasive breast cancer. Pathologists' distinction between micrometastasis (pN1mi) and isolated tumor cells [ITC; pN0(i+)] is variable using the American Joint Committee on Cancer (AJCC) Staging Manual (Sixth Edition). We sought to determine whether a set of clearly defined histologic criteria could lead to reproducible nodal classification by pathologists. Digital images of sentinel lymph node biopsies from 56 patients with small-volume nodal metastases were examined by six experienced breast pathologists (MDs), first as a pre-test, and again as a post-test after studying a training program that outlined and illustrated the classification criteria. Post-test results, after study of the training program, were significantly improved. Compared with the reference MD, agreement improved from 76.2% (pre-test kappa = 0.575; standard deviation [SD], 0.25) to 97.3% (post-test kappa = 0.947; SD, 0.049). Multirater analysis of agreement among the six MDs improved from 71.5% (pre-test kappa = 0.487; ASE, 0.039) to 95.7% (post-test kappa = 0.915; ASE, 0.037). Agreement on lobular carcinoma metastasis classification improved from 55% (23 of 42; pre-test) to 100% (42 of 42; post-test) (P < .001), and agreement on ITC classification in nodal parenchyma improved from 67.6% (69 of 102; pre-test) to 98.0% (100 of 102; post-test; P < .001). Application of current definitions for classification of small-volume nodal metastases are inconsistent, leading to variable classification of ITC and micrometastases. Reproducibility of pathologic nodal stage classification is achievable through study of a training set to clarify the AJCC criteria.

Are We Undertreating Rectal Cancer in the Elderly?

To better understand the reasons for decreased survival rates in elderly patients with rectal cancer by performing an epidemiologic evaluation of age-related differences in treatment and survival. The incidence of rectal cancer increases with older age, and localized disease can be curatively treated with stage-appropriate radical surgery. However, older patients have been noted to experience decreased survival. Patients with localized rectal adenocarcinoma were identified in the Surveillance, Epidemiology, and End Results database (1991-2002). Cancer-specific survival by age, sex, surgery type, tumor grade, lymph node status, and use of radiation therapy was evaluated using univariate and multivariate regression analysis. We identified 21,390 patients who met the selection criteria. The median age was 68 years. Each half-decade increase in age > or =70 years was associated with a 37% increase in the relative risk (RR) for cancer-related mortality (RR = 1.37; 95% confidence interval [CI], 1.33-1.42); decreased receipt of cancer-directed surgery (odds ratio [OR] = 0.56; 95% CI, 0.36-0.63); more local excision and less radical surgery (OR = 0.76; 95% CI, 0.72-0.81); less radiotherapy (OR = 0.64; 95% CI, 0.61-0.67); and greater likelihood of N0 pathologic stage classification (OR = 1.10; 95% CI, 1.05-1.15) (P < 0.0001 for each factor). The effect of age on cancer-specific mortality persisted in multivariate analysis with each half-decade increase in age > or =70 years resulting in a 31% increase in cancer-specific mortality (RR = 1.31; 95% CI, 1.25-1.36; P < 0.0001). In elderly patients, rectal cancer is characterized by decreased cancer-related survival rates that are associated with less aggressive treatment overall and decreased disease stages at presentation. Investigation into the reasons for these treatment differences may help to define interventions to improve cancer outcomes.

Assessment of the new postsurgical pathological staging classification in NSCLC

Assessment of the new postsurgical pathological staging classification in NSCLC

THE CURRENT TNM‐CLASSIFICATION OF BLADDER CARCINOMA‐IS IT AS GOOD AS WE NEED IT TO BE?

The TNM classification endorsed by the Inter- national Union Against Cancer (UICC) provides a dependable description and classification of the extent of malignant tumors. The aim of the TNM classifica- tion are as follows: to aid clinicians in the planning of treatment, to give some indication of prognosis, to assist in evaluation of the treatment results, to facili- tate the exchange of information between treatment centers, and to contribute to the continuing investiga- tion of human cancer.’ The TNM system consists of two distinct classifications, a pretreatment clinical staging classification and a postsurgical histo- pathological staging classification. Differences in the extent of disease between individual categories in the clinical staging classification and the histopathological staging classification are substantial. There is a con- siderable interest in improving accuracy of the clinical assessment of the extent of the disease which would minimize these differences. In a clinical staging of bladder cancer, improvements in imaging would be valued. A reliable clinical staging classification is para- mount to the planning of treatment and to indication of prognosis. Ideally, the staging system should be supported by an international consensus and require availability of simple and accurate diagnostic procedures. The TNM Groups of the last three International Consen- sus Meetings on Bladder Cancer have attempted to reach a consensus on the classification of bladder cancer using the TNM system, first in Antwerp in 1985,5 second in Hakone in 1987,6 and third in

Pathological stage grouping of patients with resected carcinoma of the lung

Data from a series of 569 patients with “curative” resection of non-oat cell tumors were analyzed by the life-table method to evaluate the validity of the postresection pathological staging classification suggested by the American Joint Committee. The cell types were as follows: squamous, 305; adenocarcinoma, 172; large cell, 73; and mixed, 19. Each patient was assigned a pathological TN classification on examination of the resected specimen (all patients were judged clinically to have no distant metastases—M0). There were 173 lesions classified as T1 N0, 37 as T1 N1, 212 as T2 N0, 115 as T2 N1, and 32 as either T3 with any N or N2 with any T. In analyzing the data, we identified a subset of lesions (25), initially staged as T2 N0, which were small central lesions, 3 cm or less, located distal to a lobar takeoff. Regardless of the presence of atelectasis or pneumonitis to the hilar area, patients with these lesions had a survival rate similar to that of patients with more peripherally located lesions of similar size. Three-year survival rates of 66.5% and 68.5% respectively, were noted in these two groups of patients, as compared to a 53.6% rate for the patients with lesions larger than 3 cm, which could be classified as T2 N0 regardless of their location. When lymph nodes were affected (N1), patients with small central lesions (20) had a better survival rate than the patients with either T1 N1 or other T2 N1 lesions. It is therefore suggested that all small central lesions, 3 cm or less, distal to a lobar takeoff be considered T1 lesions. Patients with T1 N1 lesions had a 3 year survival rate of only 36.7%, which is similar to the 39.8% 3-year survival rate of those with T2 N1 lesions. The other patients in Stage I had a much better survival rate: Patients with T1 NO lesions had 3 and 5 year survival rates of 68.5% and 54.4%, and those with T2 N0 lesions, 53.6% and 40.0%, respectively. Therefore, it would appear more appropriate to classify these patients as having Stage II rather than Stage I disease.