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Purpose: Oral cavity squamous cell carcinoma (OCC) can spread to the neck without apparent lymphadenopathy. Pretreatment detection or prediction of occult metastasis might contribute to proper management of clinically node-negative (cN0) OCC. We examined the role of tumour quantitative 18-fluorodeoxyglucose ( 18 F-FDG) positron emission tomography (PET)/computed tomography (CT) measurements for predicting OCC occult metastasis and survival., Methods: This study included 130 cN0 OCC patients who underwent 18 F-FDG PET/CT scanning and subsequent curative surgery and neck dissection. Maximum, peak, and mean standardized uptake value (SUV max , SUV peak , and SUV mean ), metabolic tumour volume (MTV), and total lesion glycolysis (TLG) were measured on pretreatment 18 F-FDG PET/CT. Binary logistic regression was used to identify factors predicting occult cervical metastasis. Univariate and multivariate Cox proportional hazard regression were used to find factors associated with overall survival (OS)., Results: Pathological cervical metastasis (pN +) was found in 29 (22.3%) patients. Age, tumour differentiation, lymphovascular invasion, and T classification were significantly associated with pN + (all P < 0.05). After adjustment for these factors, MTV and TLG independently predicted pN + (P < 0.05). Invasion depth, lymphovascular invasion, T and N classifications, and overall TNM stage were significantly associated with OS. After adjustment for these factors, SUV max and TLG independently predicted OS (all P < 0.05). Patients with TLG > 9.3 g had a 5.7-fold increased risk of overall mortality., Conclusions: Tumour 18 F-FDG PET/CT parameters might predict occult metastasis and survival in cN0 OCC patients.

Lymph node metastasis is one of the most important prognostic factors in oral squamous cell carcinoma. In early stage oral cancers, Depth of invasion (DOI) is a predictor for lymph node metastasis. The aim of this study was to evaluate if DOI 4 mm can be considered as a threshold for clinical decision making on elective neck dissection (END) in early oral cancer, by assessing the association of DOI and the risk of occult lymph node metastasis in early Oral squamous cell carcinoma (OSCC). A retrospective study was conducted on 319 patients with early pT1-2 OSCC who were clinically N negative. All patients underwent primary resection and END. The patients were divided into two groups based on DOI: < 4 mm and ≥ 4 mm. Nodal metastases were then noted for each group. The rate of nodal metastasis in respect to tumor size was also observed. Out of 111 patients having DOI < 4 mm only 15 (4.7%) had lymph node metastasis, whereas out of 208 patients having DOI ≥ 4 mm, 81 patients (25.4%) had neck node metastasis, with p value < 0.05. Tumors having DOI ≥ 4 mm has higher chances of occult metastasis and also increased probability of other prognostic factors like PNI and LVI, suggesting that DOI ≥ 4 mm can be considered a cut – off value for performing END. [ABSTRACT FROM AUTHOR]

Simple Summary: Neck control is a particularly important prognostic factor, and the diagnosis of neck metastasis at the initial examination is important for oral squamous cell carcinoma (OSCC). A pathologically negative neck does not guarantee future recurrence after preventive neck dissection in patients who are clinically node-negative (cN0). We hypothesized that some factors predict poor prognosis regardless of cN0 preventive neck dissection. Among 86 patients with OSCC, occult metastases were observed in 9 (10.5%), and the prognosis of these patients was local recurrence in 6 (7.0%) and neck recurrence in 9 (10.5%). The neutrophil-to-lymphocyte ratio (NLR) and vascular invasion are good markers for detecting OM. A Cox multivariable analysis identified two independent predictors of overall survival: pathologic node and laterality of END. An independent predictive factor for disease-free survival, the surgical margin, was also identified in this study. Elective neck dissection (END) is recommended for the management of patients with oral squamous cell carcinoma (OSCC) because of the risk of occult metastasis (OM). We hypothesized that some factors predict poor prognosis regardless of a cN0 END. This study aimed to investigate the predictors of OM and prognostic factors in patients with cN0 OSCC who underwent supraomohyoid neck dissection (SOHND). A retrospective cohort study design was created and implemented. The primary predictive variables in this study were OM and risk factors for poor prognosis after SOHND. A Cox proportional hazard model was used to adjust for the effects of potential confounders on the risk factors for poor prognoses. Among 86 patients with OSCC, OMs were observed in 9 (10.5%). The neutrophil-to-lymphocyte ratio (NLR) and vascular invasion are good markers for detecting OM. A Cox multivariable analysis identified two independent predictors of overall survival: pathologic node (pN) and laterality of END. An independent predictive factor for disease-free survival, the surgical margin, was also identified in this study. According to the pN classification, pN1 patients had a worse survival rate than pN2 patients. Therefore, in the case of pN1, regardless of being cN0, additional adjuvant therapy may be necessary. [ABSTRACT FROM AUTHOR]

Simple Summary: Elective management of the contralateral neck in lateralized oral squamous cell carcinoma remains a matter of debate, and current guidelines provide only little guidance in this regard. Especially patients with ipsilateral cervical lymph node metastasis are of interest since several studies showed a higher risk for contralateral metastasis in these cases. The present study is a retrospective analysis of this cohort over a 10-year period at a high-volume tumor center in Germany. The results of this study show that the prevalence of occult contralateral neck metastases is low, and that contralateral elective neck dissection should not be performed routinely in this cohort. Introduction: In lateralized oral squamous cell carcinoma (OSCC) with ipsilateral cervical lymph node metastasis (CLNM), the surgical management of the unsuspicious contralateral neck remains a matter of debate. The aim of this study was to analyze this cohort and to compare the outcomes of patients with and without contralateral elective neck dissection (END). Material and Methods: A retrospective analysis of patients with lateralized OSCC, ipsilateral CLNM (pN+) and contralateral cN0-stage was performed. Patients were divided into two groups according to the surgical management of the contralateral neck: I: END; and II: no END performed. Adjuvant radiotherapy was applied bilaterally in both groups according to individual risk. Results: A total of 65 patients (group I: 16 (24.6%); group II: 49 (75.4%)) with a median follow-up of 28 months were included. Initially, there was no case of contralateral CLNM after surgery. During follow-up, 6 (9.2%) patients presented with recurrent CLNM. In 5 of these cases (7.7%), the contralateral neck (group I: 3/16 (18.8%); group II: 2/49 (4.1%)) was affected. Increased ipsilateral lymph node ratio was associated with contralateral CLNM (p = 0.07). END of the contralateral side showed no significant benefit regarding OS (p = 0.59) and RFS (p = 0.19). Conclusions: Overall, the risk for occult contralateral CLNM in patients with lateralized OSCC ipsilateral CLNM is low. Our data suggest that END should not be performed routinely in this cohort. Risk-adapted radiotherapy of the contralateral neck alone seems to be sufficient from the oncological point of view. [ABSTRACT FROM AUTHOR]

Our laboratory previously reported an individual-level signature consisting of nine gene pairs, named 9- GPS. This signature was developed by training on microarray expression data and validated using three independent integrated microarray data sets, with samples of stage I non-small-cell lung cancer after complete surgical resection. In this study, we first validated the cross-platform robustness of 9- GPS by demonstrating that 9- GPS could significantly stratify the overall survival of 213 stage I lung adenocarcinoma ( LUAD) patients detected with RNA-sequencing platform in The Cancer Genome Atlas (TCGA; log-rank P = 0.0318, C-index = 0.55). Applying 9- GPS to all the 423 stage I- IV LUAD samples in TCGA, the predicted high-risk samples were significantly enriched with clinically diagnosed metastatic samples (Fisher's exact test, P = 0.0015). We further modified the voting rule of 9- GPS and found that the modified 9- GPS had a better performance in predicting metastasis states (Fisher's exact test, P < 0.0001). With the aid of the modified 9- GPS for reclassifying the metastasis states of patients with LUAD, the reclassified metastatic samples presented clearer transcriptional and genomic characteristics compared to the reclassified nonmetastatic samples. Finally, regulator network analysis identified TP53 and IRF1 with frequent genomic aberrations in the reclassified metastatic samples, indicating their key roles in driving tumor metastasis. In conclusion, 9- GPS is a robust signature for identifying early-stage LUAD patients with potential occult metastasis. This occult metastasis prediction was associated with clear transcriptional and genomic characteristics as well as the clinical diagnoses. [ABSTRACT FROM AUTHOR]

Nodal status is a significant predictor for survival of patients with oral squamous cell carcinoma (SCC), sentinel lymph node (SLN) biopsy, step sectioning of SLNs, and immunohistochemistry have changed the detection of tumor deposits in lymph nodes (LNs). The extent of LN metastasis is a major determinant for the staging and the prognosis of most human malignancies and often guides therapeutic decisions. Metastasis to regional lymph node (RLN) is a complex process. It is often associated with several clinical and pathological characteristics. The involvement of RLN is often, a harbinger for increased risk of metastasis. New knowledge in this area can enable the clinicians and pathologists to study and treat tumors in a more directed fashion. A molecular approach to factors that predicts the likelihood of RLN metastasis could eliminate the reoccurrence of the tumor in the form of "micrometastasis" and "skip" metastasis. The aim of this review is to discuss different modes of spread of metastasis in SCC. [ABSTRACT FROM AUTHOR]

Clinical stage II/ III esophageal cancer ( EC), as defined by the Japanese Classification, relapses at a moderately high rate even after curative resection. The number of lymph node metastases is known to be associated with tumor relapse. Recently, the prognostic significance of occult metastatic lymph nodes ( MLNs), as well as that of overt MLNs, has been reported. The aim of this study was to investigate the impact of the total number of MLNs including occult MLNs on postoperative relapse in clinical stage II/ III EC. One hundred and five patients with clinical stage II/ III EC who underwent esophagectomy accompanied by radical lymphadenectomy at the Department of Surgical Oncology in Osaka City University Hospital between January 2000 and October 2008 were included in this study. Occult MLNs, metastases not detected by hematoxylin-eosin staining, were identified by immunohistochemistry ( IHC) using antipancytokeratin antibody AE1/AE3. The clinicopathological features of occult MLNs were compared between the relapse and no relapse groups. A total of 6558 lymph nodes (1357 from two-field dissection and 5201 from three-field dissection) were examined by IHC staining; 362 overt MLNs and 143 occult MLNs were detected. The number of occult MLNs increased in proportion to the International Union Against Cancer pathological (p) N-status and p Stage. When the number of occult MLNs was added to the number of p Ns, the number of total MLNs was associated with postoperative relapse. With respect to tumor, node, metastasis stage, 6 of 22 patients (27%) who were pathological node-negative converted to node-positive by considering total MLNs. The number of N3 patients with relapse increased markedly with restaging by total MLNs. The number of total MLNs, but not overt MLNs, was an independent prognostic factor on multivariate analysis. These results suggest that occult MLNs were often found, and they were associated with postoperative relapse of resectable esophageal cancer. The total number of MLNs including occult MLNs could contribute to evaluating the precise stage of patients with esophageal cancer. [ABSTRACT FROM AUTHOR]

Abstract: Background: Dynamic sentinel node biopsy (DSNB) is used to evaluate the nodal status of patients with penile carcinoma and clinically node-negative groins. This minimally invasive procedure is usually done at the same time as the treatment of the primary tumour. Objective: Our aim was to evaluate results of so-called postresection DSNB, that is, DSNB after previous resection of the penile tumour. Design, setting, and participants: All 40 patients who had undergone DSNB after previous penile carcinoma resection with histopathologically tumour-negative margins between February 2003 and July 2009 were analysed. Twenty patients (50%) had known unilateral nodal involvement, and DSNB was used to stage the clinically normal contralateral groin. Hence the study concerned 60 groins without palpable nodes. The median time between primary tumour resection and DSNB was 2.8 mo. The technique of postresection DSNB was similar to the standard procedure. Measurements: The sentinel node visualisation rate, identification rate, histopathologic results, and outcome during follow-up were investigated. Results and limitations: A sentinel node was visualised on the lymphoscintigrams of 56 of the 60 eligible groins (93%). A sentinel node was identified intraoperatively in all these 56 groins. A median of two sentinel nodes were removed. Histopathologic analysis revealed involvement of seven groins (12%) in seven patients (18%). The median size of these metastases was 6mm. Additional dissemination was found in one completed ipsilateral inguinal node dissection specimen. No recurrences developed in the groins from which one or more tumour-free sentinel nodes had been taken during a median follow-up of 28 mo after the primary tumour resection. A potential limitation of this study is the short follow-up and relatively small cohort number. Conclusions: Postresection DSNB is a suitable procedure to stage clinically node-negative penile carcinoma after previous therapeutic primary tumour resection. The results seem similar to the favourable experience with DSNB in patients with their tumour still present. [Copyright &y& Elsevier]

The clinical relevance of isolated tumor cell (ITC: ≤0.2 mm) and micrometastasis (MM: >0.2–2.0 mm) in axillary lymph nodes (ALNs) remains unknown. The aim of this study was to determine their prognostic significance. A total of 295 patients considered as pN0 after routine histological assessment, were reevaluated with ten-level cytokeratin immunohistochemistry (IHC) and two-level hematoxylin-eosin sections. Survival rates, i.e. disease-free survival (DFS), distant disease-free survival (DDFS) and breast cancer specific survival (BCSS) were compared with those of reevaluated node-negative patients. A total of 84 patients (28%) had ITC/MM identified on IHC sections. ITC had no impact on survival at a median 8.2 years of follow-up, whereas MM showed a trend toward poorer DFS ( P = 0.091, log rank) and DDFS ( P = 0.066) and significantly reduced BCSS ( P = 0.016). In multivariate analyses, detection of MM was an independent prognostic factor for DDFS ( P = 0.025) and BCSS ( P = 0.01) in adjuvant un-treated patients. Micrometastases (MMs) in axillary lymph nodes have prognostic impact. This was not found for ITC. This finding supports the use of systemic adjuvant therapy in patients with MM. [ABSTRACT FROM AUTHOR]

PURPOSE: The purpose of this study was to determine the prognostic significance of occult lymph node metastases in colon cancer detected by cytokeratin 20 reverse transcription polymerase chain reaction. METHODS: Two hundred patients undergoing elective colonic resections were enrolled in the study. Lymph nodes from resected specimens were dissected fresh and assessed by both reverse transcription polymerase chain reaction and histopathology. Follow-up was undertaken for up to five years, and the major end point of death was recorded. Univariate survival analysis was performed by the log-rank method and the change-in-estimate method was used to construct multivariate analysis models for the effect of cytokeratin 20 reverse transcription polymerase chain reaction lymph node status on overall survival. RESULTS: A total of 2,317 lymph nodes from 200 patients were assessed by both histopathology and cytokeratin 20 reverse transcription polymerase chain reaction. Forty-eight of 141 (34 percent) histologically lymph node–negative patients had evidence of occult metastases by cytokeratin 20 reverse transcription polymerase chain reaction. An interim analysis was performed at a median of 42 (range, 23–75) months. Cytokeratin 20 reverse transcription polymerase chain reaction lymph node status was a highly significant predictor of overall survival (P < 0.0001) on univariate analysis. In addition, the number of reverse transcription polymerase chain reaction–positive lymph nodes was a significant predictor of survival in the histologically lymph node–negative group (P < 0.0001) on univariate analysis. On multivariate analysis cytokeratin 20 reverse transcription polymerase chain reaction lymph node status had independent prognostic significance for overall survival (P = 0.021; hazard ratio = 2.7) and the number of cytokeratin 20 reverse transcription polymerase chain reaction–positive lymph nodes was a significant predictor of overall survival in the histologically lymph node–negative group (P = 0.005; hazard ratio = 1.1–11.1). CONCLUSION: Cytokeratin 20 reverse transcription polymerase chain reaction has potential as a clinically useful marker for staging colorectal cancer. Further follow-up is required, but if the current trends continue, a study of the effect of adjuvant therapy in patients with occult metastases detected by cytokeratin 20 reverse transcription polymerase chain reaction is indicated. [ABSTRACT FROM AUTHOR]