American Joint Committee On Cancer/Union For International Cancer Control Research Articles

Most Siewert type II esophagogastric junction adenocarcinomas in Chinese patients lack a Barrett esophagus background

The histological origins and classification of Siewert II esophageal gastric junction (EGJ) adenocarcinomas are controversial. While the American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) staging system suggests that they be classified as esophageal cancer, some scholars insist that these cancers include a Barrett esophageal (BE) adenocarcinoma form and a gastric adenocarcinoma form. To obtain data relevant to this debate, in this study, a multi-center sample of 25 cases of Siewert II EGJ adenocarcinoma spanning a 6-year period were analyzed. The endoscopic characteristics of the tumor lesions and pathology characteristics of peritumoral mucosal background in biopsies were determined. Cases were classified as esophageal adenocarcinoma if the tumor center was located on the oral side of the EGJ and accompanied by BE. They were classified as gastric adenocarcinoma if the tumor center was located on the anal side of the EGJ and accompanied by atrophic gastritis. Of the 25 cases examined, 20 had evaluable background mucosal data, including 14 (56 %) classified as gastric adenocarcinoma and 3 (12 %) classified as BE adenocarcinoma. The remaining 3 cases (12 %) did not have signs of BE or atrophic gastritis, and thus were not classified. Siewert type II EGJ adenocarcinoma cases in China were found to be heterogeneous, with most cases being consistent with gastric adenocarcinoma. Thus, it would not be reasonable to classify all Siewert type II EGJ adenocarcinomas as esophageal cancer.

Innovative Fudan rT staging in endoscopic surgery for recurrent nasopharyngeal carcinoma.

American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) rT staging have great clinical impracticality. The aim of the present study was to establish a new rT staging to guide endoscopic surgery for the treatment of recurrent nasopharyngeal carcinoma (rNPC). This surgical rT staging (named Fudan rT staging) was constructed using two significant risk factors: the distance from the tumor margin to the internal carotid artery, and dural invasion. Log-rank and receiver operating characteristic (ROC) curve analyses were used to evaluate its effectiveness. Fudan rT staging can effectively separate the overall survival (OS) and progression-free survival (PFS) of patients with rNPC according to the different rT stages (p < 0.05). In addition, ROC analysis showed that the Fudan rT staging exhibited enhanced prognostic value for OS and PFS compared with the AJCC/UICC rT staging. The innovative Fudan rT staging has a better predictive value for the survival of patients with rNPC than AJCC/UICC rT staging.

Concepts of Pathological Staging and Prognosis in Papillary Thyroid Carcinoma.

American Joint Committee on Cancer (AJCC)/Union for International Cancer Control (AJCC/UICC) staging and American Thyroid Association (ATA) risk predication system are the best predicators of mortality and cancer recurrence, respectively, in patients with differentiated thyroid carcinoma, including papillary thyroid carcinoma. In ATA risk stratification of differentiated thyroid carcinomas, clinical features, nodal features, and pathological features are assessed. Many of the features are also assessed in pathological staging. The prognostic stage grouping of papillary thyroid carcinoma in AJCC/UICC depends on the age of the patients as well as the standard parameters-extent of tumor (T), lymph node status (N), and presence of distant metastasis (M). Major changes noted in the current pathological staging protocol include the cut-off age from 45-year to 55-year in grouping of patients, use of gross invasion of strap muscles instead of minimal microscopic extrathyroidal extensions as T3b and downstage of many prognostic groups such as those with lymph node metastases (without distant metastases) from Stage III to Stage II. The staging protocol have moved many patients with papillary thyroid carcinoma into good prognostic groups for better predication of patients' survival rates and to avoid unnecessary treatment. This new approach has been verified by different groups globally, although modifications could be expected in the future for better prognostic assessment in patients with papillary thyroid carcinoma.

Comparison of the abilities of staging and risk stratification systems to predict the long-term structural recurrence in patients with differentiated thyroid carcinoma after total thyroidectomy and radioactive iodine remnant ablation.

In patients with differentiated thyroid carcinoma (DTC), various staging and risk stratification systems have been applied to estimate long-term recurrence, which is a major issue during the postoperative follow-up period. However, the efficacy of these systems remains unclear in this context. The present historical cohort study included 510 patients with DTC who underwent a total thyroidectomy followed by radioactive iodine (RAI) remnant ablation. Enrolled patients were categorized according to the 8th edition of American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) Tumor Node Metastasis (TNM) staging system, the 2015 American Thyroid Association (ATA) initial risk stratification system, and the dynamic risk stratification (DRS) system. The ability of each system to predict long-term structural recurrence was compared using proportion of variance explained (PVE) by logistic regression models. The median follow-up period was 108 months. Structural recurrence occurred in 7.6% of the patients (n=39/510). Disease-free survival (DFS) curves of the patients within each category in the TNM staging system, the ATA initial risk stratification system, and the DRS system were significantly different (P<0.001). The PVE of the DRS system (20.7%) was higher than those of the TNM staging system and the ATA initial risk estimates. The DRS system may effectively predict long-term structural recurrence and guide long-term management and follow-up strategies in patients with DTC undergoing total thyroidectomy and RAI remnant ablation.

Comparing the 7th and 8th editions of UICC/AJCC staging system for nasopharyngeal carcinoma in the IMRT era

BackgroundTo compare the prognostic value of 7th and 8th editions of the Union for International Cancer Control/American Joint Committee on Cancer (UICC/AJCC) staging system for patients with nonmetastatic nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiotherapy and simultaneous integrated boost– intensity-modulated radiation therapy (SIB-IMRT).MethodsPatients with NPC (n = 300) who received SIB-IMRT were included. Survival by T-classification, N-classification, and stage group of each staging system was assessed.ResultsFor T-classification, nonsignificant difference was observed between T1 and T3 and between T2 and T3 disease (P = 0.066 and 0.106, respectively) for overall survival (OS) in the 7th staging system, whereas all these differences were significant in the 8th staging system (all P < 0.05). The survival curves for disease-free survival (DFS) and locoregional recurrence-free survival (LRRFS) in both staging systems were similar, except for the comparison of T2 and T4 disease for LRRFS (P = 0.070 for 7th edition; P = 0.011 for 8th edition). For N-classification, significant differences were observed between N2 and N3 diseases after revision (P = 0.046 and P = 0.043 for OS and DFS, respectively). For staging system, no significant difference was observed between IVA and IVB of 7th edition.ConclusionThe 8th AJCC staging system appeared to have superior prognosis value in the SIB-IMRT era compared with the 7th edition.

The Predictive Value of the Eighth Edition of the Clinical TNM Staging System for the Likelihood of Eye Salvage for Intraocular Retinoblastoma by Systemic Chemotherapy and Focal Therapy.

The American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) cTNM staging is emerging as a universal staging for all cancers, including retinoblastoma. Here we evaluated the predictive value of the eighth edition AJCC/UICC cTNM staging in comparison with the International Intraocular Retinoblastoma Classification for eye globe salvage by primary systemic chemotherapy and focal therapy (CRD) using logistic regression model for the probability of treatment failure. The eye salvage rate for 565 treated eyes was 95% (n=139/147) for T1 tumors (98% for T1a and 93% for T1b), 56% (n=230/410) for T2 (81% for T2a and 53% for T2b), and 0% for T3 tumors, and was 98%, 93%, 76%, and 44% for group A, B, C, and D tumors, respectively. As estimated by odds ratios, T2 were 13.6-fold more likely to fail treatment than T1, and T1b, T2a, and T2b were 2.8-, 9.4-, and 35.1-fold more likely to fail treatment than T1a, respectively. Group B, C, and D tumors were 2.8-, 12.7-, and 50.1-fold more likely to fail treatment than group A tumors, respectively. Eye salvage rate was 62% for eyes with focal seeds (3 mm close to the tumor), and 42% for eyes with diffuse seeds (clouds more than 3 mm from tumor edge) (P<0.0001). Both, the eighth edition cTNM classification and the International Intraocular Retinoblastoma Classification systems, can effectively predict eye salvage rates for retinoblastoma by CRD. Eyes with higher cT stages are more likely to experience treatment failure. Because the cT2b group is very heterogeneous, our findings suggest further division of this group based on the severity of vitreous/subretinal seeds, this should be revised in the next edition of cTNM system.

Exploration of the immune cell infiltration-related gene signature in the prognosis of melanoma.

Melanoma is a life-threatening form of skin cancer with an elevated risk of metastasis and high mortality rates. The prognosis and clinical outcomes of cancer immunotherapy in melanoma patients are influenced by immune cell infiltration in the tumor microenvironment (TME) and the expression of genetic factors. Despite reports suggesting that immune-classification may have a better prediction of prognosis compared to the American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) TNM-classification, the definition of Immunoscore in melanoma is becoming a difficult challenge. In this study, we established and verified a 7-gene prognostic signature. Melanoma patients from the Cancer Genome Atlas (TCGA) were separated into a low-risk group and a high-risk group using the median risk score. Receiver operating characteristic (ROC) analysis for overall survival (OS) showed that the area under the curve (AUC) was 0.701 for 1 year, 0.726 for 3 years, and 0.745 for 5 years, respectively. Moreover, a nomogram was constructed as a practical prognostic tool, and the AUC was 0.829 for 3 years, and 0.803 for 5 years, respectively. Furthermore, we validated the above results in two datasets from the Gene Expression Omnibus (GEO) database and the relationship between 7-gene prognostic signature and immune infiltration estimated.

The evolution of the nasopharyngeal carcinoma staging system over a 10-year period: implications for future revisions.

BackgroundThe classification criteria and staging groups for nasopharyngeal carcinoma described in the Union for International Cancer Control/American Joint Committee on Cancer (UICC/AJCC) staging system have been revised over time. This study assessed the proportion of patients whose staging and treatment strategy have changed due to revisions of the UICC/AJCC staging system over the past 10 years (ie, from the sixth edition to the eighth edition), to provide information for further refinement.MethodsWe retrospectively reviewed 1901 patients with non-metastatic nasopharyngeal carcinoma treated in our cancer center between November 2009 and June 2012. The Akaike information criterion and Harrell concordance index were applied to evaluate the performance of the staging system.ResultsIn total, 25 (1.3%) of the 1901 patients who were staged as T2a according to the sixth edition system were downgraded to T1 in the eighth edition; 430 (22.6%) staged as N0 in the sixth edition were upgraded to N1 in the eighth edition; 106 (5.6%) staged as N1/2 in the sixth edition were upgraded to N3 in the eighth edition. In addition, 51 (2.7%) and 25 (1.3%) of the study population were upstaged from stage I to stage II and stage II to stage IVa, respectively; 10 (0.5%) was downgraded from stage II to stage I. The survival curves of adjacent N categories and staging groups defined by eighth classification system were well-separated. However, there was no significant difference in the locoregional failure-free survival (P = 0.730) and disease-free survival (P = 0.690) rates between the T2 and T3 categories in the eighth edition classification system.ConclusionsModifications to the tumor-node-metastasis staging system over the past 10 years have resulted in N classification changes in numerous cases. Although the eighth edition tumor-node-metastasis staging system better predicts survival outcomes, the T classification could be simplified in future revisions.

The immune contexture and Immunoscore in cancer prognosis and therapeutic efficacy.

The international American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) tumour-node-metastasis (TNM) staging system provides the current guidelines for the classification of cancer. However, among patients within the same stage, the clinical outcome can be very different. More recently, a novel definition of cancer has emerged, implicating at all stages a complex and dynamic interaction between tumour cells and the immune system. This has enabled the definition of the immune contexture, representing the pre-existing immune parameters associated with patient survival. Even so, the role of distinct immune cell types in modulating cancer progression is increasingly emerging. An immune-based assay named the 'Immunoscore' was defined to quantify the in situ T cell infiltrate and was demonstrated to be superior to the AJCC/UICC TNM classification for patients with colorectal cancer. This Review provides a broad overview of the main immune parameters positively or negatively shaping cancer development, including the Immunoscore, and their prognostic and predictive value. The importance of the immune system in cancer control is demonstrated by the requirement for a pre-existing intratumour adaptive immune response for effective immunotherapies, such as checkpoint inhibitors. Finally, we discuss how the combination of multiple immune parameters, rather than individual ones, might increase prognostic and/or predictive power.

The impact of radioactive iodine treatment on survival among papillary thyroid cancer patients according to the 7th and 8th editions of the AJCC/TNM staging system: a SEER-based study.

Papillary thyroid cancer is a very common endocrine malignancy. The 8th American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) staging system introduced major changes. We conducted this retrospective cohort analysis to assess the benefits of radioactive iodine (RAI) according to different stratification of patients. The source of the data was the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database. From 2006 to 2015, patients with papillary thyroid cancer were included in our study. The interactions between different variables and RAI treatment were tested by multivariate Cox regression models to compare the survival differences according to RAI treatment between the patients assessed with the 7th and 8th edition of the AJCC/TNM staging system. The results of the interaction analysis and group comparisons indicated that the effects of RAI treatment on patients staged with the 7th and 8th editions were similar. Patients with early Stage, early T stage, N0 and subtotal or near total thyroidectomy benefited greatly from RAI treatment. Patients with Stage III according to the 8th edition benefited less from RAI than patients with Stage III according to the 7th edition. Patients with T1a benefited from RAI but benefited less than patients with other T stages. Patients with T3a benefited more from RAI than those with T3b. According to the 8th edition, Stage III/IV more accurately differentiates patients with advanced stage disease. These patients benefitted less from RAI treatment, which may be due to the relatively weaker iodine uptake by tumor cells. T1a patients benefitted less than patients with other T stages. The difference in RAI benefit between patients with T3a and T3b is a novel finding in our study.

Extracapsular extension of neck nodes and absence of human papillomavirus 16-DNA are predictors of impaired survival in p16-positive oropharyngeal squamous cell carcinoma.

Human papillomavirus (HPV)-driven oropharyngeal squamous cell carcinomas (OPSCCs) demonstrate superior outcome compared with HPV-negative OPSCCs. The eighth edition of the American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) tumor, lymph node, metastasis (TNM) classification (TNM 2017) modifies OPSCC staging based on p16 positivity as a surrogate for HPV-driven disease. In p16-negative OPSCCs, lymph node (N) categories include extracapsular/extranodal extension (ECE); and, in p16-positive OPSCCs, N categories are based on the number of positive neck lymph nodes omitting ECE status. The objective of the current study was to assess the prognostic impact of positive ECE status and the detection of HPV16 DNA in patients with p16-positive OPSCC. In a cohort of 92 patients with p16-positive, lymph node (N)-positive (stage III-IVB) OPSCC who underwent surgery and neck dissection, allowing for a pathologic examination of positive lymph nodes, 66 of 92 patients (71.4%) were p16-positive/HPV16 DNA-positive, 62 of 92 (67%) were ECE-positive, and 45 of 62 (72.6%) were ECE-positive, p16-positive, and HPV16 DNA-positive. Differences in outcome were assessed using Kaplan-Meier plots and Cox proportional hazard regression (CoxR) for tumor-specific survival and overall survival (OS). The mean numbers of positive lymph nodes in ECE-positive patients (5.0 positive lymph nodes; 95% CI, 3.8-6.4 positive lymph nodes) and ECE-negative patients (2.4 positive lymph nodes; 95% CI, 1.8-2.9 positive lymph nodes) were different (P=.0007). ECE affected OS and tumor-specific survival in p16-positive patients (P=.007 and P=.047, respectively) and in p16-positive/HPV16 DNA-positive patients (P=.013 and P=.026, respectively). Related to the unequal distributions of ECE-positive/HPV16 DNA-negative tumors, the TNM 2017 failed to discriminate OS in patients with UICC stage I, II, and III disease (mean OS, 54.5, 73.4, and 45months, respectively; median OS, 64.7months, not reached, and 41.1months, respectively). According to a univariate CoxR, the presence of ECE predicted impaired OS in patients with p16-positive OPSCC (hazard ratio, 3.40; 95% CI, 1.17-9.89; P=.025) and even greater impaired OS in those with p16-positive/HPV16 DNA-positive OPSCC (HR, 8.64; 95% CI, 1.12-66.40; P=.038). Multivariate CoxR confirmed ECE and HPV16 DNA detection as independent predictors. ECE and HPV16 DNA status should be included in the prognostic staging of patients with p16-positive OPSCC because several lines of evidence demonstrate their impact on survival.

Comparison of long-term prognosis for differentiated thyroid cancer according to the 7th and 8th editions of the AJCC/UICC TNM staging system.

Background:The 8th edition of the American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) tumor-node-metastasis (TNM) staging system was released with major revisions. The purpose of this retrospective study was to investigate differences between the 7th and 8th editions of the AJCC/UICC TNM staging system and to compare the predictability of prognosis between the two staging systems with patients who underwent thyroidectomy for differentiated thyroid cancer (DTC) at a single institution.Methods:A total of 3238 patients underwent thyroid operation from January 2002 to December 2006 at Yonsei University Hospital (Seoul, Korea), of which 2294 with complete clinical data and sustained follow up were enrolled. Clinicopathologic features and TNM staging by applying the 7th and 8th editions of the AJCC/UICC were analyzed retrospectively by the complete review of medical charts and pathology reports of patients. Mean follow-up duration was 132.9 ± 27.9 months.Results:A significant number of T3 patients were downstaged to T1 (838, 36.5%) and T2 (122, 5.3%). After applying the 8th edition of the AJCC/UICC TNM staging system, the number of stage I patients increased significantly from 1434 (62.5%) to 2058 (89.7%), whereas numbers of stage III and IV patients decreased significantly from 644 (28.1%) to 33 (1.4%) and from 199 (8.7%) to 17 (0.7%), respectively. According to Kaplan–Meier survival analyses and values of the Harrell’s c-index and integrated area under the curve (iAUC), the 8th edition has significantly better predictive performance for disease-free survival (DFS) and disease-specific survival (DSS) than the 7th edition.Conclusions:A significant population was downstaged after applying the 8th edition of the AJCC/UICC TNM staging system, and the 8th edition provided significantly better accuracy in predicting DFS and DSS in patients with DTC.

294P - Validation of the 8th edition of AJCC/UICC staging system for nasopharyngeal carcinoma: Results from a non-endemic cohort with long-term follow-up

BackgroundThis study aimed to validate the 8th edition of American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) TNM staging system for nasopharyngeal carcinoma (NPC) in a non-endemic region. MethodsWe recruited 614 patients with histology-proven, previously untreated, non-metastatic NPC treated by intensity-modulated radiotherapy (IMRT) at our center. Harrell’s concordance index (c-index) and time-dependent receiver operating characteristic (TD-ROC) analysis were applied to compare the prognostic discrimination between the 7th and 8th edition staging system. ResultsFor T category, the local recurrence-free survival (LRFS) Kaplan-Meier curves of T1, T2 and T3 were well separated in the 8th edition; however, LRFS did not significantly differ between T3 and T4 (P = 0.15). Moreover, the 7th edition achieved higher c-index (0.703 [95% CI, 0.618-0.788] vs. 0.686 [95% CI, 0.604-0.768]) and area under curve ([AUC], 5-year: 0.681 vs. 0.672; 10-year: 0.645 vs. 0.615) than 8th edition for LRFS. With regard to N category, the 8th edition achieved higher c-index (0.800 [95% CI, 0.755-0.847] vs. 0.757 [95% CI,.0.704-0.811]) and AUC (5-year 0.728 vs. 0.685; 10-year: 0.748 vs. 0.680) for distant metastasis-free survival. In terms of overall stage, the 8th edition also had higher c-index (0.800 [95% CI, 0.755-0.845] vs. 0.724 [95% CI, 0.676-0.773]) and AUC (5-year: 0.730 vs. 0.713; 10-year: 0.734 vs. 0.677) compared with 7th edition for overall survival. ConclusionsThe 8th edition of AJCC/UICC TNM staging system achieved significantly better prognostic discrimination than the 7th edition with regard to N category and overall stage but not T category. Legal entity responsible for the studyDepartment of Radiation Oncology, Jiangsu Cancer Hospital, Nanjing Medical University Affiliated Cancer Hospital, Jiangsu Institute of Cancer Research. FundingThe National Natural Science Foundation of China (No. 81672989; No. 81872192). DisclosureAll authors have declared no conflicts of interest.

Validation of the 8th edition of AJCC/UICC staging system for nasopharyngeal carcinoma: Results from a non-endemic cohort with 10-year follow-up

ObjectivesThis study aimed to validate the 8th edition of American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) TNM staging system for nasopharyngeal carcinoma (NPC) in non-endemic region. Materials and methodsWe recruited 607 patients with histology-proven, previously untreated, non-metastatic NPC treated by intensity-modulated radiotherapy (IMRT) at our center. Harrell’s concordance index (c-index) and Akaike information criterion (AIC) were applied to compare the prognostic discrimination between the 7th and 8th edition staging system. ResultsFor T category, the local recurrence-free survival (LRFS) Kaplan-Meier curves of T1, T2 and T3 were well separated in the 8th edition; however, LRFS did not significantly differ between T3 and T4 (P = 0.166). Moreover, the 7th edition achieved higher c-index (0.702 [95% CI, 0.618–0.787] vs. 0.685 [95% CI, 0.604–0.767]) and lower AIC (766.1 vs. 770.8) than 8th edition for LRFS. With regard to N category, the 8th edition achieved higher c-index (0.796 [95% CI, 0.749–0.843] vs. 0.751 [95% CI, 0.696–0.805]) and lower AIC (1439.4 vs. 1471.9) for distant metastasis-free survival. In terms of overall stage, the 8th edition also had higher c-index (0.798 [95% CI, 0.753–0.844] vs. 0.721 [95% CI, 0.672–0.770]) and lower AIC (1963.9 vs. 2007.2) compared with the 7th edition for overall survival. Furthermore, interval validation by bootstrapping the sample randomly for ~100–1000 times also validated above findings. ConclusionThe 8th edition of AJCC/UICC TNM staging system achieved significantly better prognostic discrimination than the 7th edition with regard to N category and overall stage but not T category.

Clinical Value of Lymph Node Ratio Integration with the 8th Edition of the UICC TNM Classification and 2015 ATA Risk Stratification Systems for Recurrence Prediction in Papillary Thyroid Cancer

Recently, the 2015 American Thyroid Association (ATA) risk stratification and the 8th edition of the American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) TNM staging system were released. This study was conducted to assess the clinical value of the lymph node ratio (LNR) as a predictor of recurrence when integrated with these newly released stratification systems, and to compare the predictive accuracy of the modified systems with that of the newly released systems. The optimal LNR threshold value for predicting papillary thyroid cancer (PTC) recurrence was 0.17857 using the Contal and O’Quigley method. The 8th edition of the AJCC/UICC TNM staging system with the LNR and the 2015 ATA risk stratification system with the LNR were significant predictors of recurrence. Furthermore, calculation of the proportion of variance explained (PVE), the Akaike information criterion (AIC), Harrell’s c index, and the incremental area under the curve (iAUC) revealed that the 8th edition of the TNM staging system with the LNR, and the 2015 ATA risk stratification system with the LNR, showed the best predictive performance. Integration of the LNR with the TNM staging and the ATA risk stratification systems should improve prediction of recurrence in patients with PTC.

Retrieved lymph nodes from different anatomic groups in gastric cancer: a proposed optimal number, comparison with other nodal classification strategies and its impact on prognosis

BackgroundThe optimal number of retrieved lymph nodes (LNs) in gastric cancer (GC) is still debatable and previous studies proposing new classification alternatives mostly focused on the number of retrieved LNs without proper consideration on the anatomic nodal groups’ location. Here, we assessed the impact of retrieved LNs from different nodal location groups on the survival of GC patients.MethodsStage I–III gastric cancer patients who had radical gastrectomy were investigated. LN grouping was determined according to the 13th edition of the JCGC. The optimal cut-off values of retrieved LNs in different LN groups (Group 1 and 2) were calculated, based on which a proposed nodal classification (rN) simultaneously accounting the optimal number and location of retrieved LNs was proposed. The performance of rN was then compared to that of LN ratio, log-odds of metastatic LNs (LODDs) and the 8th edition of the Union for International Cancer Control/American Joint Committee on Cancer (UICC/AJCC) N classification.ResultsThe optimal cut-off values for Group 1 and 2 were 13 and 9, respectively. The 5-year overall survival (OS) was higher for patients in retrieved Group 1 LNs > 13 (vs. Group 1 LNs ≤ 13, 63.2% vs. 57.9%, P = 0.005) and retrieved Group 2 LNs > 9 (vs. Group 2 LNs ≤ 9, 72.5% vs. 60.7%, P = 0.009). Patients staged as pN0–3b were sub classified using this Group 1 and 2 nodal analogy. The OS of pN0–N2 patients in retrieved Group 1 LNs > 13 or Group 2 LNs > 9 were superior to those in retrieved Group 1 LNs ≤ 13 and Group 2 LNs ≤ 9 (All P < 0.05); except for pN3 patients. The rN classification was formulated and demonstrated better 5-year OS prognostication performance as compared to the LNR, LODDs, and the 8th UICC/AJCC N staging system.ConclusionsThe retrieval of > 13 and > 9 LNs for Group 1 and Group 2, respectively, could represent an alternative lymph node retrieval approach in radical gastrectomy for more precise survival prognostication and minimizing staging migration, especially if > 16 LNs is found to be difficult.

Essential updates 2017/2018: Recent topics in the treatment and research of gastric cancer in Japan.

Recent developments in diagnostic technology, accumulated clinical effort and established evidence have boosted early detection and drastically improved early and long‐term outcomes of gastric cancer. However, gastric cancer continues to be one of the most aggressive and life‐threatening malignancies among all cancers and is a global health problem. Between January 2017 and December 2018, various fascinating reports of managements and research were published, including the new 15th Japanese Classification of Gastric Carcinoma reflecting the 8th American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) tumor, node and metastasis (TNM) classification (October 2017) and the new Gastric Cancer Treatment Guidelines version 5 (January 2018). Moreover, pivotal molecular features of gastric cancer were clarified by the worldwide cancer genome project, and various treatment targets and biomarkers such as circulating DNAs and microRNAs were detected. Novel treatment options using programmed cell death protein 1 immune checkpoint inhibitors have been started. In this review, we summarize the recent topics of classification, guidelines, and clinical and basic research in order to bring new insights to gastric cancer treatment.

Unlocking the Potential of Saliva-Based Test to Detect HPV-16-Driven Oropharyngeal Cancer.

The incidence of human papillomavirus (HPV)-positive oropharyngeal cancer (OPC) is rising in high-income countries, including Australia. Increasing evidence suggests that accurate HPV testing is pivotal for clinical decision making and treatment planning in these patients. Recently, the eighth edition of the American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) tumor–node–metastasis (TNM) staging system for OPC (based on the p16INK4a (p16) status) was proposed and has been implemented. However, the applicability of this new staging system is still far from clear. In our study, n = 127 OPC patients from Queensland, Australia were recruited, and the tumor p16 expression in these patients was examined using immunohistochemical (IHC) analysis. HPV-16 genotyping, viral load, and physical status (episomal versus integrated) in the saliva samples of OPC patients were determined using the qPCR method. A good inter-rater agreement (k = 0.612) was found between tumor p16 expression and oral HPV-16 infection in OPC. Importantly, according to the eighth edition staging system, HPV-16 DNA viral load (>10 copies/50 ng) was significantly associated with the advanced stages of OPC. In concordance with previous studies, a mixed HPV-16 form (partially or fully integrated) was predominately found in OPC patients. Taken together, our data support HPV-16 detection in saliva as a screening biomarker to identify people within the community who are at risk of developing OPC.

A simplified T classification based on the 8th edition of the UICC/AJCC staging system for nasopharyngeal carcinoma.

Objective: This study aimed to establish a simplified T classification based on the 8th edition of the Union for International Cancer Control/American Joint Committee on Cancer (UICC/AJCC) staging system for nasopharyngeal carcinoma (NPC).Methods: In total, 325 patients with NPC were included in this study. All patients underwent magnetic resonance imaging, and the staging criteria were recorded. These patients were subjected to staging with the 8th edition of the UICC/AJCC staging system for NPC.Results: Involvement of the oropharynx, nasal cavity, adjacent soft tissue (medial pterygoid, lateral pterygoid, and prevertebral muscles), cervical vertebra, orbit, and hypopharynx were always accompanied by other equivalently or more advanced T-stage classifications. All cases with involvement of the paranasal sinuses showed skull base erosion. The majority of cases with involvement of the pterygoid structure showed skull base erosion.Conclusion: According to the simplification principle, the following new T classification based on the 8th edition of the UICC/AJCC staging system was established: T1, tumor confined to nasopharynx, or beyond the nasopharynx without parapharyngeal involvement; T2, tumor with extension to the parapharyngeal space; T3, tumor with infiltration to bony structures at the skull base; T4, tumor with intracranial extension, involvement of the cranial nerves or parotid gland, and/or extensive soft tissue infiltration beyond the lateral surface of the lateral pterygoid muscle. Validation with a large series of patients is needed.

Laparoscopic liver resection for intrahepatic cholangiocarcinoma

Background: Cholangiocarcinoma is the most common biliary tract malignancy, and the second most common type of primary liver cancer. It is more common in Asia but its incidence in North America is increasing. CCA can be categorized as intrahepatic (iCCA) or extrahepatic (perihilar – pCCA/distal – dCCA). There are three main staging systems: American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC); Liver Cancer Study Group of Japan (LCSGJ); and National Cancer Center of Japan (NCCN). Its clinical presentation is unspecific, and it varies depending on tumor location and stage disease. Combined interpretation with different diagnostic modalities is necessary. Methods: A 73-year-old female presented with mild abdominal discomfort and back pain to her primary care physician. Laboratorial exams were requested, and elevated liver enzymes were noted. Abdominal ultrasound was performed that showed left-sided bile duct dilation. Patient underwent an abdominal MRI that identified tortuous and markedly dilated left intrahepatic bile ducts with lobular enhancing intraductal mass with restricted diffusion in the left main hepatic duct measuring approximately 2.3 x 0.9 x 0.8 cm. ERCP with biopsy was made, and a polypoid lesion in the left bile duct was seen. The papillary epithelium was consistent with high-grade dysplasia with possible intraductal papillary neoplasm or cholangiocarcinoma. Laparoscopic surgery was indicated. Patient underwent a cholecystectomy, hepatoduodenal lymphadenectomy, left hepatectomy, and en bloc caudate resection. Results: The Patient was in supine position. General anesthesia was induced. A supraumbilical incision was made. The abdomen was entered without difficulty. Hasson trocar was placed, pneumoperitoneum established. The laparoscope was induced, and the abdomen was explored. The patient had no signs of metastatic or peritoneal disease. The left lobe appeared atrophied, and the right lobe appeared quite hypertrophied. No signs of underlying liver disease. Therefore, 2 additional right-sided 12-mm trocars, an epigastric 5 and a left side 5 trocars were placed. An enlarged hepatic artery lymph node was identified, resected and sent for frozen, it was negative for neoplasia. Cholecystectomy and hepatoduodenal lymphadenectomy were performed. The intrahepatic lesion was resectable, and the caudate lobe appeared potentially involved. It was decided to perform a left hepatectomy with en bloc caudate lobe resection. Specimen was analyzed by Pathology, that confirmed grossly and microscopically widely negative margins. The surface of the liver was cut, and packed with gauze and Surgicel. This was completely dry. There was adequate arterial and portal inflow with biliary drainage to the right lobe of the liver, and no sign of bile leak. Surgicel SNoW and Surgicel gauze were placed against the cut surface of the liver, and closed the specimen extraction site with multiple figure-of-eight 0 Vicryl sutures, and desufflated the abdomen through the trocars, removed the trocars, and closed the 12-mm trocar with a single interrupted 0 Vicryl, and closed the skin with running 4-0 subcuticular stitch and covered with Dermabond. Counts were reported as correct. No complications. No drains. Estimated blood loss was 300 mL. Patient tolerated the surgery well, and was discharged on postoperative day 3. Conclusion: Surgery is the only potentially curative therapeutic option for Cholangiocarcinoma. Minimally invasive approach is challenging, and not widely performed by surgeons. It requires expertise in liver and laparoscopic technique. Despite this, it is feasible, and safe for intrahepatic Cholangiocarcinoma. There are no differences in oncologic outcomes. Blood loss seems to be higher when open surgery is performed, and lymphadenectomy higher in minimally invasive approaches. There are no significant differences between length of hospital stay and complication rates. Laparoscopic liver resection is a treatment modality that should be considered for selected patients with intrahepatic cholangiocarcinoma.