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Introduction Because several articles have reported a prognostic association with the radiologic features of ground-glass opacity, we explored whether the histologic presence of a lepidic component had similar significance. Methods We retrospectively evaluated 380 consecutive surgically resected lung adenocarcinomas (ADCs) of pathologic (p)stage IA. The tumors were classified into lepidic-positive and lepidic-negative ADCs. Clinicopathologic characteristics, radiographic ground-glass opacity status, and disease-free survival were compared between lepidic-positive and lepidic-negative ADCs and between part-solid and solid nodules on computed tomography images. Results Of the 380 cases, 176 (46.3%) were lepidic-positive ADCs. Of the overall patients with pT1, lepidic-positive ADCs were found to have significantly better recurrence-free survival (5 y, 95.4% versus 87.0%, p = 0.005), but this significance was not reproduced in pT1 subcategories (pT1a, pT1b, and pT1c). Furthermore, the presence of the lepidic component was not an independent prognostic factor in the multivariate analysis (hazard ratio = 0.46 [95% confidence interval: 0.19–1.14], p = 0.09). We also analyzed the extent of the lepidic component with 10% incremental valuables. Although we found that a 10% or greater extent of lepidic component made the recurrence-free survival difference the largest, a clear prognostic impact was not obtained with this cutoff point. Conclusions Although lepidic-positive ADCs tended to have a favorable outcome, the lepidic component was not a clear independent prognostic factor in pstage I ADC.

PURPOSE To verify the superiority of irinotecan plus cisplatin over etoposide plus cisplatin as postoperative adjuvant chemotherapy for patients with pathologic stage I-IIIA, completely resected, high-grade neuroendocrine carcinoma (HGNEC) of the lung. METHODS This was a randomized, open-label, phase III study on patients with completely resected stage I-IIIA HGNEC of the lung. They were randomly assigned to receive either etoposide (100 mg/m2, days 1-3) plus cisplatin (80 mg/m2, day 1) or irinotecan (60 mg/m2, days 1, 8, 15) plus cisplatin (60 mg/m2, day 1) up to four cycles. The primary end point was relapse-free survival (RFS) in the intention-to-treat population. This trial was registered with the Japan Registry of Clinical Trials (jRCTs031180216). RESULTS Between April 2013 and October 2018, 221 patients were enrolled (etoposide plus cisplatin arm, 111 patients; irinotecan plus cisplatin arm, 110 patients). In the second interim analysis, early termination of the trial was recommended because of futility. At a median follow-up of 24.1 months, the 3-year RFS was 65.4% for etoposide plus cisplatin and 69.0% for irinotecan plus cisplatin, with a hazard ratio of 1.076 (95% CI, 0.666 to 1.738; one-sided log-rank P = .619). Grade 3-4 adverse events were more frequent in the etoposide plus cisplatin arm, with febrile neutropenia (20% of 109 patients v 4% of 107 patients) and neutropenia (97% v 36%) being the most common. Meanwhile, grade 3-4 anorexia (6% v 11%) and diarrhea (1% v 8%) were more frequently observed in the irinotecan plus cisplatin arm. CONCLUSION Irinotecan plus cisplatin is not superior to etoposide plus cisplatin for improving RFS in patients with completely resected HGNEC; thus, etoposide plus cisplatin remains the standard treatment.

INTRODUCTION: The purpose of the study is to genomically characterize the biology and related therapeutic opportunities of prognostically important predominant histological subtypes in lung adenocarcinoma (LUAD). METHODS: We identified 604 patients with stage I-III LUAD who underwent complete resection and targeted next-generation sequencing using the MSK-IMPACT platform. Tumors were classified according to predominant histologic subtype and grouped by architectural grade (lepidic [LEP], acinar or papillary [ACI/PAP], and micropapillary or solid [MIP/SOL]). Associations between clinicopathologic factors, genomic features, mutational signatures, and recurrence were examined within subtypes and, when appropriate, quantified using competing-risks regression, with adjustment for pathologic stage and extent of resection. RESULTS: MIP/SOL tumors had higher tumor mutational burden (p

Background Patients with rectal cancer who achieve complete clinical response after neoadjuvant chemoradiation have been managed nonoperatively. Thirty percent of these patients may develop a local regrowth, and salvage resection with radical surgery is usually recommended. However, selected patients could be offered additional organ preservation by local excision. We hypothesized that patients with baseline T2 who underwent neoadjuvant therapy (for the specific purpose of achieving a complete clinical response) were more likely to harbor recurrent disease at an earlier stage and amenable to organ preservation strategies (local excision) when compared with T3/T4 (undergoing neoadjuvant chemoradiation for oncologic reasons). Objective The purpose of this study was to compare patients with local regrowth requiring salvage resection according to their baseline stage. Design This was a retrospective review of consecutive patients with nonmetastatic distal rectal cancer undergoing neoadjuvant chemoradiation. Settings The study included 2 independent tertiary centers with institutional watch-and-wait organ preservation programs. Patients Consecutive patients with distal rectal cancer (cT2-4N1-2M0) managed by watch and wait and local regrowth from 2 institutions were included. Main outcomes measures Final pathologic features and surgical and oncologic outcomes were compared according to baseline staging. Results A total of 73 of 257 patients experienced local regrowth. cT2 presented similar to ypT, ypN, R0, and abdominal perineal resection rates (p > 0.05) at the time of salvage when compared with cT3 to cT4. Patients with cT2 at baseline were more likely to undergo an organ preservation procedure for salvage (56.2% vs 26.5%; p = 0.03). Overall and disease-free survival after salvage were similar between groups irrespective of the type of surgery for the regrowth. Limitations Retrospective study, small sample size, and possible inaccurate baseline staging. Conclusions Although patients with baseline cT2 rectal cancer had similar pathologic stage at the time of recurrence, these patients were more likely to continue an organ preservation pathway after local regrowth through transanal local excision when compared with cT3 to cT4. Despite differences in the use of radical salvage resection, there were no differences in oncologic outcomes. See Video Abstract at http://links.lww.com/DCR/B254. CIRUGIA DE RESCATE CON PRESERVACION DE ORGANO PARA PACIENTES CON RECIDIVA LOCAL LUEGO DE WATCH & WAIT: ?SIGUE SIENDO POSIBLE?: Los pacientes con cancer rectal que logran una respuesta clinica completa luego de la quimiorradiacion neoadyuvante han sido tratados de forma no quirurgica. El treinta por ciento de estos pacientes pueden desarrollar un nuevo crecimiento local y generalmente se recomienda la reseccion de rescate con cirugia radical. Sin embargo, en pacientes seleccionados se podria ofrecer la posibilidad de preservacion de organo mediante escision local. Se formulo la hipotesis de que los pacientes con estadio clinico inicial T2 y sometidos a terapia neoadyuvante (con el proposito especifico de lograr una respuesta clinica completa) tenian mas probabilidades de presentar una recurrencia local en una etapa mas temprana y suceptibles de estrategias de preservacion de organo (escision local) en comparacion con T3 / T4 (sometidos a nCRT por razones oncologicas).Comparar los pacientes con recidiva local que requirieron cirugia de rescate de acuerdo con su estadio inicial.Revision retrospectiva de pacientes consecutivos con cancer de recto distal no metastasico sometidos a quimiorradiacion neoadyuvante.Dos centros terciarios independientes con programas institucionales de preservacion de organo - Watch & Wait.Pacientes consecutivos con cancer rectal distal (cT2-4N1-2M0) manejados por Watch & Wait y recidiva local.Las caracteristicas patologicas finales, los resultados quirurgicos y oncologicos se compararon de acuerdo con la estadificacion inicial.Un total de 73 de 257 pacientes presentaron recidiva local. cT2 presentaron similares ypT, ypN, R0 y tasas de reseccion abdominoperineal (p>0,05) en el momento del rescate en comparacion con cT3-4.Los pacientes con cT2 de base tuvieron mas probabilidades de someterse a un procedimiento de preservacion de organo durante el rescate (56,2% frente a 26,5%; p = 0,03). Supervivencia general y DFS despues del rescate fueron similares entre los grupos, independientemente del tipo de cirugia para la recidiva.Estudio retrospectivo, tamano de muestra pequeno, la posible estadificacion basal inexacta.Aunque los pacientes con cancer rectal cT2 de base presentaron estadio patologico similar en el momento de la recidiva, estos pacientes tuvieron mas probabilidades de continuar una via de preservacion de organo luego de una recidiva local a traves de la escision local transanal en comparacion con cT3-4. A pesar de las diferencias en el uso de la reseccion radical de rescate, no hubo diferencias en los resultados oncologicos. Consulte Video Resumen en http://links.lww.com/DCR/B254.

Objectives: The cornerstone of the management of cervical cancer (CC) traditionally relies on clinical examination (CE) of tumor size (TS) and local extension of disease. The goal of this study is to determine the accuracy of CE in comparison to final pathology (FP) in early operable CC. Methods: This is a multi-center retrospective review of patients with early CC (FIGO 2009 Stage IB1, IIA1). CE of TS, parametrial invasion (PI), and vaginal involvement (VI) were compared to FP. Results: The final analysis included 135 patients. Overall, there was a significant difference between CE of TS compared to FP; mean error of 1.22 cm (p

The melanoma expert panel devised the evidence-based eighth edition American Joint Committee on Cancer staging system by conducting vigorous analyses of stage I, II, and III patients from the International Melanoma Database and Discovery Platform. Key changes in the eighth edition are regarding subcategorization of T1, M1, pathologic stage grouping of stage I and III, and refining the definitions and terminologies used in the staging system. As the knowledge of tumor biology improves, the staging of melanoma will continue to evolve to enable betterment of care.

Background The clinical pathologic stages (stage I, II, III-IV) of hepatocellular carcinoma (HCC) are closely linked to the clinical prognosis of patients. This study aims at investigating the gene expression and mutational profile in different clinical pathologic stages of HCC. Methods Based on the TCGA-LIHC cohort, we utilized a series of analytical approaches, such as statistical analysis, random forest, decision tree, principal component analysis (PCA), to identify the differential gene expression and mutational profiles. The expression patterns of several targeting genes were also verified by analyzing the Chinese HLivH060PG02 HCC cohort, several GEO datasets, HPA database, and diethylnitrosamine-induced HCC mouse model. Results We identified a series of targeting genes with copy number variation, which is statistically associated with gene expression. Non-synonymous mutations mainly existed in some genes (e.g.,TTN, TP53, CTNNB1). Nevertheless, no association between gene mutation frequency and pathologic stage distribution was detected. The random forest and decision tree modeling analysis data showed a group of genes related to different HCC pathologic stages, including GAS2L3 and SEMA3F. Additionally, our PCA data indicated several genes associated with different pathologic stages, including SNRPA and SNRPD2. Compared with adjacent normal tissues, we observed a highly expressed level of GAS2L3, SNRPA, and SNRPD2 (P = 0.002) genes in HCC tissues of our HLivH060PG02 cohort. We also detected the high expression pattern of GAS2L3, SEMA3F, SNRPA, and SNRPD2 in the datasets of GSE102079, GSE76427, GSE64041, GSE121248, GSE84005, and the qPCR assay using diethylnitrosamine-induced HCC mouse model. Moreover, SEMA3F and SNRPD2 protein were highly stained in the HCC tissues of the HPA database. The high expression level of these four genes was associated with the poor survival prognosis of HCC cases. Conclusions Our study provides evidence regarding the gene expression and mutational profile in different clinical pathologic stages of TCGA HCC cases. Identifying four targeting genes, including GAS2L3, SNRPA, SNRPD2, and SEMA3F, offers insight into the molecular mechanisms associated with different prognoses of HCC.

The goal was to develop a classification of degenerative spondylolisthesis (DS) and concurrent lumbar spinal stenosis (LSS) based on pathologic stage and determine how these subtypes of DS affect outcomes for minimally invasive decompression. Patients who underwent microendoscopic laminotomy for single-level LSS with DS were included. Degenerative spondylolisthesis pathologic staging was defined as early, advanced, or end stage, based on percent slippage (10% slippage), degree of dynamic instability (3 mm), and disc height. Less than 10% required additional surgery; 5% required subsequent fusion, and all these patients were in the advanced stage DS group.

BACKGROUND Although important for determining long-term outcome, pathologic stage of hepatocellular carcinoma (HCC) is difficult to predict before surgery. Current state-of-the-art magnetic resonance imaging (MRI) using gadoxetic acid provides many imaging features that could potentially be used to classify single HCC as pT1 or pT2. AIM To determine which gadoxetic acid-enhanced MRI (EOB-MRI) findings predict pathologic stage T2 in patients with solitary HCC (cT1). METHODS Pre-operative EOB-MRI findings were reviewed in a retrospective cohort of patients with solitary HCC. The following imaging features were examined: Hyperintensity in unenhanced T2-weighted images, hypointensity in unenhanced T1-weighted images, arterial enhancement, corona enhancement, washout appearance, capsular appearance, hypointensity in the tumor tissue during the hepatobiliary (HB) phase, peritumoral hypointensity in the HB phase, hypointense rim in the HB phase, intratumoral fat, hyperintensity on diffusion-weighted imaging, hypointensity on apparent diffusion coefficient map, mosaic appearance, nodule-in-nodule appearance, and the margin (smooth or irregular). Surgical pathology was used as the reference method for tumor staging. Univariate and multivariate analyses were performed to identify predictors of microvascular invasion or satellite nodules. RESULTS There were 39 (34.2%; 39 of 114) and 75 (65.8%; 75 of 114) pathological stage T2 and T1 HCCs, respectively. Large tumor size (≥ 2.3 cm) and two MRI findings, i.e., corona enhancement [odds ratio = 2.67; 95% confidence interval: 1.101-6.480] and peritumoral hypointensity in HB phase images (odds ratio = 2.203; 95% confidence interval: 0.961-5.049) were associated with high risk of pT2 HCC. The positive likelihood ratio was 6.25 (95% confidence interval: 1.788-21.845), and sensitivity of EOB-MRI for detecting pT2 HCC was 86.2% when two or three of these MRI features were present. Small tumor size and hypointense rim in the HB phase were regarded as benign features. Small HCCs with hypointense rim but not associated with aggressive features were mostly pT1 lesions (specificity, 100%). CONCLUSION Imaging features on EOB-MRI could potentially be used to predict the pathologic stage of solitary HCC (cT1) as pT1 or pT2.

The objective of this retrospective study is to compare the outcomes of laparoscopic and open surgery for T2 gallbladder cancer (GBC) performed at our hospital for last 13 years.Of 247 GBC patients who were treated at our hospital between Apr 2004 and Apr 2017, 151 patients with pathologic stage T2 were reviewed. Patients were divided into laparoscopic surgery group (LS group) and open (OS group). Medical recordings were reviewed to check perioperative outcomes, overall survival rates, and disease free survival rates.Fifty-five patients in LS group and 44 in OS met the inclusion criteria. Incidences of postoperative complication were similar between two groups (12.7% vs 13.6%, p = 1.000). Average postoperative hospital stay was significantly shorter in LS group (5.8 vs 9.5 days, p 0.001). LS group showed significantly higher disease free survival rate (p = 0.0171). There was no significant difference in terms of disease free survival between T2N0 (p = 0.107) and T2N1 patients (p = 0.969) of LS group and OS group. In terms of overall survival rate there was no significant difference (p = 0.116). Overall survival rate was also not significantly different between T2N0 (p = 0.0941) and T2N1 (p = 0.579) patients of LS group and OS group.Laparoscopic approach for treatment of T2 GBC was comparable to open approach in terms of disease free survival, overall survival and complication rate. Further prospective study with higher number of patients should be done to confirm this result in the future.

Purpose: This study aimed to find risk factors for colon cancer progression with bioinformatics methods, and validated by clinical patients. Methods: Differentially expressed genes (DEGs) between colon cancer tissues and normal colon tissues were extracted from The Cancer Genome Atlas (TCGA) database using R software, amounted to 8,051. DEGs between pathologic stage I+II and stage III+IV amounted to 373, and were compared with DEGs of cancer/normal analyzed above to get the intersection of both. Ninety-six intersected DEGs were identified and defined as progressive DEGs of colon cancer. Then these 96 progressive DEGs were studied by Gene ontology and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway analysis using the DAVID database and visualizing by R software. A protein-protein interaction (PPI) network and functional modules were established using the STRING database. Further, an overall survival (OS) curve was drawn via the GEPIA website based on the CGA database and six progressive DEGs were found to be involved with OS of colon cancer patients. The Linkedomics website was used for detailed analysis of specific subsets of TNM. Results: Pregnancy specific glycoprotein (PSG), vitamin digestion, and absorption were confirmed to promote the progression of colon cancer. Furthermore, NTF4 was found to be associated with both OS and each subset of TNM; therefore, defined as a key risk factor for colon cancer progression. Further analysis of NTF4 expression using clinical data showed it acted as a key risk factor and diagnosis marker for colon cancer progression. Conclusion: NTF4 is a risk factor contributing to colon cancer progression and associated with overall survival.

BackgroundLoco-regional recurrences (LRR) following breast-conserving surgery (BCS) remain a heterogeneous class of disease that has significant variation in its biological behavior and prognosis.MethodsTo delineate the spatiotemporal patterns of LRR after BCS, we analyzed the data of 4325 patients treated with BCS from 2006 to 2016. Clinico-pathological and treatment specific factors were analyzed using the Cox proportional hazards model to identify factors predictive for LRR events. Recurrence patterns were scrutinized based on recurrence type and recurrence-free interval (RFI). Annual recurrence rates (ARR) were compared according to recurrence type and molecular subtype.ResultsWith a median follow-up of 66 months, 120 (2.8%) LRRs were recorded as the first site of failure. Age, pathologic stage, and molecular subtype were identified as predictors of LRR. The major recurrence type was ipsilateral breast tumor recurrence, which mainly (83.6%) occurred ≤5y post surgery. In the overall population, ARR curves showed that relapse peaked in the first 2.5 years. Patients with regional nodal recurrence, shorter RFI, and synchronous distant metastasis were associated with a poorer prognosis. HER2-positive disease had a higher rate of LRR events, more likely to have in-breast recurrence, and had an earlier relapse peak in the first 2 years after surgery.ConclusionsLRR risk following BCS is generally low in Chinese ethnicity. Different recurrence patterns after BCS were related to distinct clinical outcomes. Management of LRR should be largely individualized and tailored to the extent of disease, the molecular profile of the recurrence, and to baseline clinical variables.

Objective: This study aimed to identify the novel microRNAs (miRNAs) for early diagnosis of bladder cancer. Materials and Methods: Differentially expressed miRNAs between early and advanced bladder cancer were identified by differential expression analysis, using miRNA-seq data from The Cancer Genome Atlas (TCGA). The optimal subset of feature miRNAs for pathologic stage prediction was acquired by Random Forest algorithm and was used to construct a support vector machine (SVM) classifier. The performance of the SVM classifier in predicting the progression of bladder cancer samples was validated using an independent validating dataset. An miRNA-regulated target gene network was finally constructed and functional annotation were performed for the target genes. Results: A total of 52 significantly differentially expressed miRNAs were identified between early and advanced bladder cancer samples and 17 of these miRNAs were identified to be feature miRNAs. The 17 feature miRNAs were used to construct an SVM classifier, which showed a high performance in pathologic stage prediction for both training and validating dataset. Besides, our functional annotation analysis showed that the feature miRNAs were significantly involved in biological processes and pathways related to extracellular matrix process and PI3K/Akt signaling. Conclusions: The optimal subset of miRNAs may act as potential therapeutic targets and diagnostic markers of bladder cancer.

Introduction: The International Association for the Study of Lung Cancer proposed a new grading criteria for invasive adenocarcinoma. However, its utility has not been validated. Methods: Patients who underwent complete resection of lung adenocarcinoma were included in this study. Then, they were divided into the following three groups on the basis of the criteria recently proposed by the International Association for the Study of Lung Cancer: grade 1, lepidic predominant tumor, with less than 20% of high-grade patterns; grade 2, acinar or papillary predominant tumor, with less than 20% of high-grade patterns; and grade 3, any tumor with greater than or equal to 20% of high-grade patterns. Results: Recurrence-free survival (RFS) was significantly different among the proposed grades (p < 0.001). The RFS of patients upgrading from current grade 2 (papillary or acinar predominant tumor) to proposed grade 3 (5-y RFS, 65.2%) was significantly worse than that of patients with proposed grade 2 (77.1%, hazard ratio = 1.882, 95% confidence interval: 1.236–2.866) but not significantly different from that of patients with grade 3 in both the current (micropapillary or solid predominant tumor) and proposed criteria (53.2%, hazard ratio = 0.761, 95% confidence interval: 0.456–1.269). Among patients with pathologic stage 0 or I, RFS was well stratified by the new grading system (p < 0.001) but not among patients with stage II or III (p = 0.334). In the multivariable analysis, the new grading was not a predictive factor of RFS. Conclusions: Although the proposed grading system well stratified RFS in patients with pathologic stage 0 or I lung adenocarcinoma, there is room for improvement.

Objectives Compare outcomes of open and minimally invasive staging (MIS) for patients with early stage ovarian clear cell carcinoma (OCCC). Methods Patients with clinical stage I OCCC, no history of another tumor and known mode of surgery, diagnosed between 2012–2015 were drawn from the National Cancer Database. Impact of MIS on overall survival (OS) of patients who at least one month of follow-up was assessed with the log-rank test. A Cox model was constructed to control for confounders. Results A total of 1402 patients were identified; 438 (31.2%) had MIS. Conversion rate was 11.6%. Laparotomy and MIS groups were comparable in terms of age, race, insurance, co-morbidities, chemotherapy administration, rate of capsule rupture and final pathologic stage distribution. Patients who had MIS had shorter hospital stay (median 2 vs 4 days, p Conclusions For patients with apparent early stage OCCC, open and MIS staging have similar oncologic outcomes.

This chapter attempts to familiarize the reader with the pathologic stage classification AJCC–TNM staging system by presenting selected examples.

Background Effect of neoadjuvant chemotherapy (NAC) for pancreatic ductal adenocarcinoma (PDAC) has remained under investigation. We investigated its effect from a unique perspective and discussed its application. Patients and methods We retrospecively analyzed consecutive 131 PDAC patients who underwent pancreatoduodenectomy and distal pancreatectomy. Clinicopathologic data at surgery and postoperative prognosis were compared between patients who underwent upfront surgery (UFS) (n = 64) and those who received NAC (n = 67), of which 62 (92.5%) received gemcitabine plus S-1 (GS). The GS regimen resulted in about 15% of partial response and 85% of stable disease in a previous study which analyzed a subset of this study subjects. Results Tumor size was marginally smaller, degree of nodal metastasis and rate of distant metastasis were significantly lower, and pathologic stage was significantly lower in the NAC group than in the UFS group. In contrast, significant differences were not observed in histopathologic features such as vessel and perineural invasions and differentiation grade. Notably, disease-free and overall survivals were similar between the two groups adjusted for the pathologic stage, suggesting that effects of NAC, including macroscopically undetectable ones such as control of micro-metastasis and devitalizing tumor cells, may not be remarkable in the majority of PDAC, at least with respect to the GS regimen. Conclusions NAC may be useful in downstaging and improving prognosis in a small subset of tumors. However, postoperative prognosis may be determined at the pathologic stage of resected specimen with or without NAC. Therefore, NAC may be applicable to borderline resectable and locally advanced PDAC for enabling surgical resection, but UFS would be desirable for primary resectable PDAC.

PURPOSE The relapse rate after primary retroperitoneal lymph node dissection (RPLND) for patients with pathologic stage (PS) IIA nonseminomatous germ cell tumors (NSGCTs) is 10%-20% but increases to ≥ 50% for PS IIB disease. We report our experience with 2 cycles of adjuvant etoposide plus cisplatin (EP×2) after therapeutic primary RPLND. PATIENTS AND METHODS All patients with PS II NSGCT seen at Memorial Sloan Kettering Cancer Center from March 1989 to April 2016 and who were planned to receive EP×2 were included. Each cycle consisted of cisplatin 20 mg/m2 and etoposide 100 mg/m2 on days 1 through 5 at 21-day intervals. Demographic characteristics, histopathologic features, therapeutic and survival outcomes were recorded. RESULTS Of 156 patients, 30 (19%) had pathologic N1, 122 (78%) had pathologic N2 (pN2), and 4 (3%) had pathologic N3 (pN3) disease. The median number of involved lymph nodes was 3 (range, 1-37 nodes), and the median size of the largest involved node was 2.0 cm (range, 0.4-7.0 cm); extranodal extension was present in 69 patients (45%). Embryonal carcinoma was the most frequent RPLND histology, present in 143 patients (92%). One hundred fifty patients (96%) received EP×2, five received EP×1 and one received EP×4. With a median follow-up of 9 years, 2 patients (1.3%; 1 patient each with pN2 and pN3 disease) experienced relapse; both patients remain continuously disease free at more than 5 and 22 years after salvage chemotherapy. Three patients died, all unrelated to NSGCT, yielding 10-year disease-specific, relapse-free, and overall survival rates of 100%, 98%, and 99%, respectively. CONCLUSION Adjuvant EP×2 for PS II NSGCT is highly effective, has acceptable toxicity, and incurs less drug cost than 2 cycles of bleomycin, etoposide, and cisplatin. Inclusion of bleomycin in this setting is not necessary.

Background Oral squamous cell carcinoma (OSCC) is a major lethal malignant cancer of the head and neck region, yet its molecular mechanisms of tumourigenesis are still unclear. Patients and methods We performed weighted gene co-expression network analysis (WGCNA) on RNA-sequencing data with clinical information obtained from The Cancer Genome Atlas (TCGA) database. The relationship between co-expression modules and clinical traits was investigated by Pearson correlation analysis. Furthermore, the prognostic value and expression level of the hub genes of these modules were validated based on data from the TCGA database and other independent datasets from the Gene Expression Omnibus (GEO) database and the Human Protein Atlas database. The significant modules and hub genes were also assessed by functional analysis and gene set enrichment analysis (GSEA). Results We found that the turquoise module was strongly correlated with pathologic T stage and significantly enriched in critical functions and pathways related to tumourigenesis. PPP1R12B, CFD, CRYAB, FAM189A2 and ANGPTL1 were identified and statistically validated as hub genes in the turquoise module and were closely implicated in the prognosis of OSCC. GSEA indicated that five hub genes were significantly involved in many well-known cancer-related biological functions and signaling pathways. Conclusion In brief, we systematically discovered a co-expressed turquoise module and five hub genes associated with the pathologic T stage for the first time, which provided further insight that WGCNA may reveal the molecular regulatory mechanism involved in the carcinogenesis and progression of OSCC. In addition, the five hub genes may be considered candidate prognostic biomarkers and potential therapeutic targets for the precise early diagnosis, clinical treatment and prognosis of OSCC in the future.

Objectives Rete testis invasion by germ cell tumors is frequently concomitant with lymphovascular or spermatic cord invasion (LVI/SCI); independent implications for staging are uncertain. Methods In total, 171 seminomas and 178 nonseminomatous germ cell tumors (NSGCTs; 46 had 1%-60% seminoma component) came from five institutions. Metastatic status at presentation, as a proxy for severity, was available for all; relapse data were unavailable for 152. Rete direct invasion (ReteD) and rete pagetoid spread (ReteP) were assessed. Results ReteP and ReteD were more frequent in seminoma than NSGCT. In seminoma, tumor size bifurcated at 3 cm or more or less than 3 cm predicted metastatic status. Tumors with ReteP or ReteD did not differ in size from those without invasions but were less than with LVI/SCI; metastatic status or relapse did not show differences. In NSGCT, ReteP/ReteD did not correlate with size, metastatic status, or relapse. Conclusions Findings support retaining American Joint Committee for Cancer pathologic T1 stage designation for rete testis invasion and pT1a/pT1b substaging of seminoma.

Use of adjuvant chemotherapy (AC) following neoadjuvant chemoradiation (nCRT) is controversial in rectal cancer (RC). We assessed a multi-institutional database to determine if there was benefit from AC for pathologic stage II RC patients and whether the addition of oxaliplatin to fluoropyrimidine (OXAC) therapy impacted outcomes.We included patients who underwent nCRT and had pathologic stage II (ypT3/4 ypN0) tumors. Disease-free survival and overall survival were assessed. Multivariate Cox models adjusting for age, sex, Eastern Cooperative Oncology Group, high-risk features (pT4, poor differentiation,12 nodes removed, lymphovascular/perineural invasion, or obstruction/perforation), and clinical stage were constructed.Of 485 patients, 73.6% received AC, of which 25.5% received OXAC. Patients receiving AC were younger (median age 61 vs. 64; P=0.003) and had higher rates of total mesorectal excision (81.5% vs. 78.9%; P=0.049), but had similar high-risk features, performance status, clinical stage, margin status, preoperative carcinoembryonic antigen, and nCRT regimen. In univariate analysis, overall survival was improved with fluoropyrimidine AC compared with no AC or OXAC (P=0.049), but not disease-free survival (P=0.33). In multivariate analysis, any AC, fluoropyrimidine AC, or OXAC did not improve outcomes. After stratifying patients by the presence of high-risk features, elevated carcinoembryonic antigen, margin status, or preoperative clinical stage, we did not identify a group with improved outcomes following AC.In this multi-institutional cohort of yp stage II RC patients, we failed to identify a group that derives benefit from AC following nCRT. The addition of oxaliplatin did not appear to improve outcomes when compared with fluoropyrimidine alone.

Background The prognosis of patients with pathologic stage T3a renal cell carcinoma (RCC) that is up-staged from a small renal tumor remains controversial. We evaluated the prognosis of patients with RCC who were up-staged from clinical stage T1 to pathologic stage T3a. Methods We retrospectively reviewed the data of 3431 patients who were surgically treated for clinical stage T1 RCC. The survival outcomes were compared using Kaplan-Meier and Cox proportional analyses. Results Among the clinical stage T1 patients, 215 (6.3%) were finally up-staged to pathologic stage T3a. Patient age (HR 1.302, 95% CI 1.018–1.046, p 0.5). Conclusions Patients up-staged from clinical stage T1 to pathologic stage T3a RCC showed shorter survival outcomes than those without upstaging. However, partial nephrectomy, compared with radical nephrectomy, showed comparable outcomes in patients who were up-staged.

To investigate the feasibility of active surveillance (AS) in biopsy Gleason score (GS) 3 + 4 prostate cancer (PCa), we compared the outcomes of biopsy GS 3 + 3 and 3 + 4 PCa after radical prostatectomy.We analyzed the data of 1491 patients undergoing radical prostatectomy for biopsy GS 3 + 3 or 3 + 4 PCa who fulfilled the low-risk criteria of the National Comprehensive Cancer Network guidelines regardless of GS. The favorable GS 3 + 4 group was defined as having core involvement ≤ 50%, prostate-specific antigen density ≤ 0.2 ng/mL/cmThe GS 3 + 4 group showed significantly worse pathologic outcomes, including pathologic GS, pathologic stage, and seminal vesicle invasion rate (all P .001), as well as worse biochemical recurrence-free survival (P .001) than the GS 3 + 3 group. However, the favorable GS 3 + 4 subgroup showed no significant differences in the pathologic outcomes (all P.05) and in biochemical recurrence-free survival (P = .817) compared to the GS 3 + 3 group.Despite the application of low-risk criteria, GS 3 + 4 PCa patients showed significantly worse outcomes than GS 3 + 3 patients. However, favorable GS 3 + 4 patients showed comparable clinicopathologic outcomes with GS 3 + 3 patients, suggesting possible expansion of AS for the favorable GS 3 + 4 group.