Development and validation of a new clinical staging system to predict survival for esophageal squamous cell carcinoma patients: Application of the nomogram

IntroductionSurvival of patients with the same clinical stage varies widely and effective tools to evaluate the prognosis utilizing clinical staging information is lacking. This study aimed to develop a clinical nomogram for predicting survival of patients with Esophageal Squamous Cell Carcinoma (ESCC).Materials and methodsOn the basis of data extracted from the SEER database (training cohort, n = 3375), we identified and integrated significant prognostic factors for nomogram development and internal validation. The model was then subjected to external validation with a separate dataset obtained from Jinling Hospital of Nanjing Medical University (validation cohort, n = 1187). The predictive accuracy and discriminative ability of the nomogram were determined by concordance index (C-index), Akaike information criterion (AIC) and calibration curves. And risk group stratification was performed basing on the nomogram scores.ResultsOn multivariable analysis of the training cohort, seven independent prognostic factors were identified and included into the nomogram. Calibration curves presented good consistency between the nomogram prediction and actual observation for 1-, 3-, and 5-year OS. The AIC value of the nomogram was lower than that of the 8th edition American Joint Committee on Cancer TNM (AJCC) staging system, whereas the C-index of the nomogram was significantly higher than that of the AJCC staging system. The risk groups stratified by CART allowed significant distinction between survival curves within respective clinical TNM categories.ConclusionsThe risk stratification system presented better discriminative ability for survival prediction than current clinical staging system and might help clinicians in decision making.     

Validation of the American Joint Committee on Cancer 8th edition staging system for the pancreatic ductal adenocarcinoma

Background & aimsThe American Joint Commission on Cancer (AJCC) 8th edition staging system for pancreatic ductal adenocarcinoma (PDA) contains several significant changes. This study aimed to validate the AJCC 8th edition staging system of PDA.MethodsWe analyzed patients with resected PDA between 2001 and 2017 using the Korean Pancreatic Cancer (K-PaC) registry. Overall survival (OS) was estimated using the Kaplan-Meier survival curves and compared via the log-rank test.ResultsIn total, 701 resected PDA patients were identified. During a median follow-up of 24.5 months, the median OS was 21.7 months. Meanwhile, the median OS of each stage according to the AJCC 8th edition was 73.5 months (stage IA), 41.9 months (stage IB), 24.2 months (stage IIA), 18.3 months (stage IIB), and 16.8 months (stage III). However, the new N-category (pN1 vs. pN2) did not subdivide prognosis, although the lymph node ratio (i.e., the ratio of the number of LN involved to the number of examined LN) did. Although pT3 and pN2 belong under stage III, pN2 has a significantly longer median OS than pT3 (16.9 months vs 11.2 months; p < 0.01).ConclusionThe AJCC 8th edition staging system appropriately stratifies the prognosis of PDA patients. However, the cutoff of the N-category is not statistically valid, and the new stage III includes a heterogeneous category (pN2 and pT4). Therefore, we propose that stage III be divided into stage IIIA (Tany N2 M0) and stage IIIB (T4 Nany M0).     

The prognostic relevance of histologic subtype in appendiceal adenocarcinoma

BackgroundThe aim of this population-based study was to determine the prognostic value of the histologic subtypes mucinous (MAC), non-mucinous (AC) and signet ring cell (SRCC) adenocarcinoma among patients with appendiceal cancer.Methods and materialsData from the Netherlands Cancer Registry (NCR) of patients with primary appendiceal adenocarcinomas with MAC, AC and SRCC histologic subtype, diagnosed between 2001 and 2015 were used (n = 675). To categorize patients according to the recent histopathological classification, the NCR was linked with the Dutch Pathology Registry (PALGA). Log-rank tests and Kaplan-Meier analyses were performed to estimate overall survival (OS), and the cox proportional hazards model was run to identify prognostic factors.ResultsAC was the most frequently encountered histologic subtype (50.9%), followed by MAC (35.8%) and SRCC (13.3%). In locoregional disease, histologic subtype was not a prognostic factor for OS with 5-year survival rates for patients with AC, MAC and SRCC of 60.0%, 60.5% and 69.6% respectively (p = 0.68). Metastatic disease was more common in SRCC (53.8%) than in MAC (38.8%) and AC (23.4%) (p < 0.0001). Median OS for patients with metastatic disease was 12.6, 27.7 and 18.2 months in AC, MAC and SRCC respectively (p < 0.005). MAC was associated with higher survival compared to AC (HR 0.48, 95%CI 0.34–0.69). In subanalyses, MAC was only a positive prognostic factor compared to AC in patients with peritoneal metastases (HR 0.42, 95%CI 0.28–0.62).ConclusionHistologic subtype had no prognostic relevance in locoregional or systemic metastatic disease in appendiceal adenocarcinoma. In peritoneal metastases, mucinous histologic subtype was a favorable prognostic factor, compared to non-mucinous and signet ring cell subtype.     

Laparoscopic approach for T4 colon cancer can be associated with poor prognosis in right-sided T4b tumours

IntroductionAlthough recent studies have demonstrated the safety of laparoscopic surgery in T4 colon cancer, some patients could have poor prognosis. In this study, we aimed to analyse the risk factors affecting oncologic outcome of laparoscopic surgery.Materials and methodsAmong the 1033 T4 colon cancer patients collected from a multicentre database (2004–2017), 584 patients (458 T4a and 126 T4b) underwent laparoscopic approach for radical surgery. Risk factors associated with 3-year disease-free survival (DFS) and overall survival (OS) were evaluated through multivariate analysis. In addition, subgroups were classified using a combination of risk factors, and the survival rate was evaluated.ResultsDuring this period, 188 (32.2%) had recurrence, and 151 (25.9%) died. In the multivariate analysis for oncologic outcome, elevated carcinoembryonic antigen level (hazard ratio [HR] 1.37) and absence of adjuvant chemotherapy (HR 1.60) were associated with poor DFS. T4b (HR 1.56, 1.46), right-sided location (HR 1.52, 1.42), and open conversion (HR 2.70, 2.12) were independently associated with both poor DFS and OS. When four subgroups were analysed through the combination of tumour location and T stage, the DFS and OS rates were significantly lower in patients with right-sided T4b cancer than in other groups (log-rank p < 0.001).ConclusionRight-sided T4b colon cancer for laparoscopic surgery may lead to poor oncologic outcome. This approach could be a caution in suspected cases preoperatively.     

Factors associated with sentinel lymph node status and prognostic role of completion lymph node dissection for thick melanoma

IntroductionSentinel lymph node (SLN) biopsy is useful for the prognostic stratification of patients with thick melanoma. Identifying which variables are associated with SLN involvement and establishing risk in different subgroups of patients could be useful for guiding the indication of SLN biopsy. The value of complete lymph node dissection (CLND) in patients with a positive SLN biopsy is currently under debate.Materials and methodsTo identify factors associated with SLN involvement in thick melanoma we performed a multicentric retrospective cohort study involving 660 patients with thick melanoma who had undergone SLN biopsy. To analyze the role of CLND in thick melanoma patients with a positive SLN biopsy, we built a multivariate Cox proportional hazards model for melanoma-specific survival (MSS) and disease-free survival (DFS) and compared 217 patients who had undergone CLND with 44 who had not.ResultsThe logistic regression analysis showed that age, histologic subtype, ulceration, microscopic satellitosis, and lymphovascular invasion were associated with nodal disease. The CHAID (Chi-squared Automatic Interaction Detection) decision tree showed ulceration to be the most important predictor of lymphatic involvement. For nonulcerated melanomas, the histologic subtype lentigo maligna melanoma was associated with a low rate of SLN involvement (4.3%). No significant differences were observed for DFS and MSS between the CLND performed and not-performed groups. Nodal status on CLND was associated with differences in DFS and MSS rates.ConclusionWe identified subgroups of thick melanoma patients with a low likelihood of SLN involvement. CLND does not offer survival benefit, but provides prognostic information.     

Comparison of anatomic and non-anatomic resections for very early-stage hepatocellular carcinoma: The importance of surgical resection margin width in non-anatomic resection

BackgroundThe superiority of anatomic resection (AR) over non-anatomic resection (NAR) for very early-stage hepatocellular carcinoma (HCC) has remained a topic of debate. Thus, this study aimed to compare the prognosis after AR and NAR for single HCC less than 2 cm in diameter.MethodsConsecutive patients with single HCC of diameter less than 2 cm who underwent curative hepatectomy between 1997 and 2017 were included in this retrospective study.ResultsIn total, 159 patients were included in this study. Of these, 52 patients underwent AR (AR group) and 107 patients underwent NAR (NAR group). No significant differences were noted in recurrence-free survival (RFS) and overall survival (OS) between the AR and NAR groups (P = 0.236 and P = 0.363, respectively). Multivariate analysis revealed that low preoperative platelet count and presence of satellite nodules were independent prognostic factors of RFS and OS. Wide surgical resection margin did not affect RFS (P = 0.692) in the AR group; however, in the NAR group, RFS was found to be higher with surgical resection margin widths ≥1 cm than with surgical resection margin widths <1 cm (P = 0.038).ConclusionsPrognosis was comparable between the NAR and AR groups for very early-stage HCC with well-preserved liver function. For better oncologic outcomes, surgeons should endeavor in keeping the surgical resection margin widths during NAR ≥1 cm.     

Clinical presentation and prognosis of adenosquamous carcinoma of the pancreas – Matched-pair analysis with pancreatic ductal adenocarcinoma

IntroductionAdenosquamous carcinoma of the pancreas (ASCP) is a rare subtype of pancreatic adenocarcinoma. The aim of this study was to investigate the characteristics and outcomes of ASCP in comparison to pancreatic ductal adenocarcinoma (PDAC).Materials and methodsAll patients with ASCP treated between December 2001 and December 2017 were identified from a prospective database. Clinicopathological and follow-up data were analyzed. A nested case-control-study with matched-pair analysis was performed to compare overall survival of ASCP and PDAC.ResultsOf 4009 patients undergoing surgery for pancreatic adenocarcinoma 91 patients had ASCP. Compared to PDAC ASCP were larger (4.0 vs. 3.2 cm; p < 0.0001), more frequently involved lymph nodes (88% vs. 78%; p = 0.0216), more frequently showed poor differentiation (G3: 79% vs. 36%; p < 0.0001) and more frequently were located in the pancreatic tail (19% vs. 10%; p = 0.0179). Overall median post-resection-survival was shorter in ASCP (10.8 vs. 20.5 months in PDAC; p = 0.0085), but 5-year survival rates were comparable (18.2% vs. 17.5%). After matching for the unevenly distributed prognostic factors survival after resection of ASCP and PDAC was comparable (p = 0.8301). Localization in the head or several parts of the pancreas, high CA 19-9 levels, and M1 disease were independent predictors of survival in patients with ASCP.ConclusionASCP is more aggressive with poorer differentiation and higher rates of lymph node metastases compared to PDAC. In spite of a shorter median survival, 5-year survival rates after surgical resection of about 18% can be expected in ASCP and support resection as part of a multimodal therapy as the treatment of choice in this rare cancer.     

Role of stratifin (14-3-3 sigma) in adenocarcinoma of gallbladder: A novel prognostic biomarker

BackgroundGallbladder cancer (GBC) is a rare and fatal biliary tract malignancy. Genetic derangements are one of many factors that determine the prognosis of GBC. In this study, the expression of the stratifin (SFN) gene encoding 14-3-3 sigma protein, which is reported to be associated with the metastatic property of cholangiocarcinoma cells, was investigated in GBC.Material and methodsFormalin-fixed paraffin-embedded cancer (n = 37) and non-cancer control tissues (n = 14) of gallbladders from patients who underwent surgical resection from January 2006 to May 2015 were retrieved. The expression of SFN normalized with that of ACTB was determined using RT-qPCR. Multivariate analysis of factors affecting disease-free survival (DFS) and overall survival (OS) including the type of SFN expression was performed.ResultThe average expression level of SFN in cancer was higher than that in control tissues (p = 0.002). The relative SFN expression in cancer tissue was classified as overexpression (n = 14) and control level expression (n = 23) according to the receiver operating characteristic (ROC) curves for discriminating early GBC recurrence or metastasis after surgery. The SFN overexpression group was associated with lower rates of distant metastasis and early tumor recurrence following resection. The univariate analysis demonstrated factors affecting DFS, including resection margin (p < 0.001), lymphovascular invasion (p = 0.040), perineural invasion (p = 0.046), and SFN expression (p < 0.001). The multivariate analysis revealed that the resection margin (p = 0.019) and SFN expression (P = 0.040) were independent prognostic factors of DFS.ConclusionTo achieve the longest survival, margin-free resection is recommended. The overexpression of SFN in GBC is associated with better prognosis, lower rates of early cancer recurrence, and distant metastasis following resection. SFN expression might be a novel prognostic biomarker in GBC treatment. Further studies to elucidate the role of SFN might unveil its clinical benefit in cancer treatment regimens.     

A new nomogram for recurrence-free survival prediction of gastrointestinal stromal tumors: Comparison with current risk classification methods

BackgroundThis study aimed to build a new risk stratification nomogram for gastrointestinal stromal tumors (GISTs) focused on a popular factor Ki-67 to enable individualized and precise predictions of the most suitable candidates for imatinib therapy.MethodsWe retrospectively collected clinicopathologic data of the patients diagnosed with GISTs from January 1998 to December 2015 at Southern Medical University Nanfang Hospital as the experiment group. And patients with GISTs at the Sun Yat-sen University Cancer Center from January 2007 to December 2012 were included as the validation group. The nomogram was built using Kaplan-Meier method and the Cox proportional hazards regression model. The receiver operating characteristic (ROC) curves were established to compare the discriminative ability of the new nomogram with other risk stratification systems, including the modified National Institute of Health (modified NIH) criteria, Armed Forces Institute of Pathology (AFIP) criteria, Memorial Sloan Kettering Cancer Center (MSKCC) prognostic nomogram, and contour maps.ResultsIn univariate analysis, the tumor size, site, mitotic count, tumor rupture and Ki-67 labeling index were significant factors (all P < 0.05) and included in the Cox model to build our nomogram. According to the ROC curve, our new nomogram showed the largest AUC value (0.778) compared with that of the other classification methods (contour maps, AUC = 0.743; AFIP, AUC = 0.719; MSKCC, AUC = 0.712; and modified NIH, AUC = 0.719).ConclusionOur new nomogram exhibits an excellent performance and might become a potential risk stratification to support therapeutic decision-making for GISTs.     

Comprehensive analysis of prognostic value of lymph node staging classifications in patients with head and neck squamous cell carcinoma after cervical lymph node dissection

PurposeTo determine the optimal threshold of examined lymph node (ELN) number from cervical lymph node dissection for head and neck squamous cell carcinoma (HNSCC). Further to compare the prognostic value of multiple lymph node classification systems and to determine the most suitable scheme to predict survival.MethodsA total of 20991 HNSCC patients were included. Odds ratios (ORs) for negative-to-positive node stage migration and hazard ratios (HRs) for survival were fitted using the LOWESS smoother. Structural breakpoints were determined by the Chow test. The R square, C-index, likelihood ratio, and Akaike information criterion (AIC) were used to compare the prognostic abilities among AJCC N stage, number of positive lymph nodes (pN), positive lymph node ratio (LNR) and log odds of positive lymph nodes (LODDS) stages.ResultsA minimal threshold ELN number of fifteen had the discriminatory capacities for both stage migration and survival. LODDS stages had the highest R square value (0.208), C-index (0.736) and likelihood ratio (2467) and the smallest AIC value (65874). LODDS stages also showed prognostic value in estimating patients with AJCC N0 stage. A novel staging system was proposed and showed good prognostic performance when stratified by different primary sites.ConclusionFifteen lymph nodes should be examined for HNSCC patients. LODDS stage allows better prognostic stratification, especially in N0 stage. The proposed staging system may serve as precise evaluation tools to estimate postoperative prognoses.     

Prognostic value of a new staging system based on the retrieved number and metastatic rate of LNs in gastric cancer with ≤15 retrieved LNs

ObjectiveTo investigate a reasonable lymph node (N) staging system for gastric cancer patients with ≤15 retrieved lymph nodes (LNs).MethodsThe clinicopathological and follow-up data of patients with ≤15 LNs were obtained from the US Surveillance, Epidemiology, and End Results (SEER) database to analyze the impact of the number of retrieved LNs and metastatic status on the prognosis. In addition, external validation was achieved with data from two medical centers in China.ResultsA total of 18,139 gastric cancer patients with 1–15 retrieved LNs from the SEER database were enrolled and randomly divided into the training group and the internal validation group. A new LN staging system, mNr staging (mNr0-4; 5 stages), was established according to the number of retrieved LNs and the metastatic rate. Compared with the TNM and TNrM staging systems (established by Wang J; misclassification rates of 50.4% and 62.5%, respectively), the mTNrM staging system had a lower misclassification rate (23.4%). Furthermore, there was a significant difference in the 5-year overall survival (OS) rate between the mTNrM staging subgroups (p < 0.05); however, no significant difference was found in the 5-year OS rate of partial adjacent stages in the TNM (8th edition) and TNrM (p > 0.05) staging systems. Similar results were obtained in the external validation cohort.Conclusion: mNr and mTNrM staging systems can efficiently distinguish a survival difference in patients who undergo gastrectomy with ≤15 retrieved LNs, with more accurate predictions of the 5-year OS rate of patients compared with the TNM and TNrM staging systems.     

Lymph node yield in the pathological staging of resected nonmetastatic colon cancer: The more the better?

IntroductionGuidelines recommend regional lymphadenectomy with a lymph node yield (LNY) of at least 12 lymph nodes (LN) for adequate colon cancer (CC) staging. LNY ≥22LN may improve survival, especially in right-sided CC [Lee et al., Surg Oncol, 27(3), 2018]. This multicentric retrospective cohort study evaluated the impact of LNY and tumor laterality on CC staging and survival.Materials and methodsPatients with stage I-III CC that underwent surgery from 2012 to 2018 were grouped according to LNY: <22 and ≥ 22. Primary outcomes were LN positivity (N+ rate) and disease-free survival (DFS). Overall survival (OS) was the secondary outcome. Exploratory analyses were performed for laterality and stage.ResultsWe included 795 patients (417 < 22LN, 378 ≥ 22LN); 53% had left-sided CC and 29%/37%/38% had stage I/II/III tumors. There was no association between LNY ≥22LN and N+ rate after adjustment for grade, T stage, lymphovascular invasion (LVI) and perineural invasion; a trend for a higher N+ rate in left-sided CC was identified (interaction p = 0.033). With a median follow-up of 63.6 months for DFS and 73.2 months for OS, 254 patients (31.9%) relapsed and 207 (26.0%) died. In multivariate analysis adjusted for age, ASA score, laparoscopic approach, T/N stage, mucinous histology, LVI and adjuvant chemotherapy, LNY ≥22LN was significantly associated with both DFS (HR 0.75, p = 0.031) and OS (HR 0.71, p = 0.025). Restricted cubic spline analysis showed a more significant benefit for right-sided CC.ConclusionLNY ≥22LN was associated with longer DFS and OS in patients with operable CC, especially for right-sided CC.     

Association of primary tumor location with long-term oncological prognosis following hepatectomy for hepatocellular carcinoma:A multicenter propensity score matching analysis

PurposeThere is a striking laterality in the site of hepatocellular carcinoma (HCC), with a strong predominance for the right side; however, the impact of primary tumor location on long-term prognosis after hepatectomy of HCC remains unclear. This study aimed to investigate the effect of primary tumor location on long-term oncological prognosis after hepatectomy for HCC.Patients and methodsData of consecutive patients undergoing curative hepatectomy for HCC between 2008 and 2017 were analyzed. Overall survival (OS) and recurrence-free survival (RFS) of left-sided HCC (LS group) and right-sided HCC (RS group) were compared by using propensity score matching (PSM) analysis. COX regression analysis was performed to assess the adjusted effect of tumor location on long-term oncological prognosis.ResultsOf the 2799 included patients, 707 (25.3%) and 2092 (74.7%) were in the LS and RS groups, respectively. Using PSM analysis, 650 matched pairs of patients were created. In the PSM cohort, median OS (66.0 vs. 72.0 months, P = 0.001) and RFS (28.0 vs. 51.0 months, P < 0.001) were worse among patients in the LS group compared to individuals in the RS group. After further adjustment for other confounders using multivariable COX regression analyses, HCC located on the left side remained independently associated with worse OS and RFS.ConclusionTumors located on the left side are associated with poorer OS and RFS after hepatectomy for HCC. Careful surgical options selection and frequent follow-up to improve long-term survival may be justified for HCC patients with left-sided primary tumors.     

The prognostic role of in-hospital transfusion of fresh frozen plasma in patients with cholangiocarcinoma undergoing curative-intent liver surgery

IntroductionMajor hepatectomy for perihilar and intrahepatic cholangiocarcinoma (CCA) is often associated with a significant intraoperative blood loss and the requirement for perioperative transfusion of blood products. The aim of this study was to investigate the oncological impact of fresh frozen plasma (FFP) transfusion during hospitalization in patients undergoing hepatectomy for CCA as adverse effects have been described in other malignancies.Material and methodsPatients undergoing hepatectomy for CCA from 2010 to 2019 at a single institution were eligible for this study. Survival analysis was carried out according to Kaplan-Meier and the associations of cancer-specific (CSS) and recurrence-free survival (RFS) with in-hospital application of FFP and other clinico-pathological characteristics were assessed using Cox regression models. Perioperatively deceased patients were excluded from the analysis.ResultsA total of 219 CCA patients were included in this survival analysis of which 53.0% (116/219) received FFP during hospitalization. Patients receiving in-hospital FFP showed a median CCS of 33 months (3-year-CSS = 46%, 5-year-CSS = 29%) compared to 83 months (3-year-CSS = 55%, 5-year-CSS = 53%) in patients who did not receive in-hospital FFP (p = 0.006 log rank). Further, in-hospital FFP was identified as an independent predictor of oncological outcome in multivariable analysis (CSS: HR = 1.71, p = 0.016; RFS: HR = 1.89, p = 0.003).ConclusionIn a large European cohort of patients, in-hospital transfusion of FFP was identified as a novel independent prognostic marker in CCA patients undergoing curative-intent liver surgery. A restrictive transfusion policy is therefore recommended to improve long-term outcome in these patients.     

The prognostic value of lymph node ratio in Medullary thyroid carcinoma: A multi-center study

IntroductionThe lymph node ratio (LNR), which represents the proportion of metastatic lymph nodes resected, has been found to be a prognostic variable in several cancers, but data for Medullary thyroid carcinoma (MTC) are sparse. The aim of this study was to determine the value of the LNR in predicting outcome in patients with MTC.Materials and methodsA retrospective multicenter study design of 107 patients with MTC who underwent total thyroidectomy with neck dissection between 1984 and 2016. The association of LNR with patient and tumor characteristics and prognostic factors was evaluated.ResultsStudy population consisted of 53.3% female, mean age at diagnosis was 50.3 ± 18.4 years; 16.8% had inherited MTC. LNR was positively correlated with tumor size (p = 0.018) and inversely correlated with age at diagnosis (p = 0.024). A higher LNR was associated with extrathyroidal extension (p < 0.001), multifocality (p = 0.001), bilateral tumor (p = 0.002), distant metastases (p < 0.001), and tumor recurrence (OR = 14.7, p < 0.001). LNR was also correlated to postoperative calcitonin levels (p < 0.001) and carcinoembryonic antigen (p = 0.011). LNR >0.1 was associated with shorter disease-specific survival in patients at risk: tumor larger than 20 mm at diagnosis (p = 0.013), sporadic MTC (p = 0.01), and age above 40 years at diagnosis (p = 0.004). Cox multivariate survival analysis revealed LNR as the only significant independent factor for disease free survival (p = 0.005).ConclusionsThis study showed that LNR correlates well with patient and tumor characteristics and prognostic variables. We suggest that LNR should be considered an important parameter for predicting outcome in MTC.     

A novel fluorescent c-met targeted imaging agent for intra-operative colonic tumour mapping: Translation from the laboratory into a clinical trial

BackgroundThe c-Met protein is overexpressed in many gastrointestinal cancers. We explored EMI-137, a novel c-Met targeting fluorescent probe, for application in fluorescence-guided colon surgery, in HT-29 colorectal cancer (CRC) cell line and an in vivo murine model.MethodsHT-29 SiRNA transfection confirmed specificity of EMI-137 for c-Met. A HT-29 CRC xenograft model was developed in BALB/c mice, EMI-137 was injected and biodistribution analysed through in vivo fluorescent imaging. Nine patients, received a single intravenous EMI-137 bolus (0.13 mg/kg), 1–3 h before laparoscopic-assisted colon cancer surgery (NCT03360461). Tumour and LN fluorescence was assessed intraoperatively and correlated with c-Met expression in eight samples by immunohistochemistry.Findingsc-Met expression HT-29 cells was silenced and imaged with EMI-137. Strong EMI-137 uptake in tumour xenografts was observed up to 6 h post-administration. At clinical trial, no serious adverse events related to EMI-137 were reported. Marked background fluorescence was observed in all participants, 4/9 showed increased tumour fluorescence over background; 5/9 had histological LN metastases; no fluorescent LN were detected intraoperatively. All primary tumours (8/8) and malignant LN (15/15) exhibited high c-Met protein expression.InterpretationEMI-137, binds specifically to the human c-Met protein, is safe, and with further refinement, shows potential for application in fluorescence-guided surgery.     

Laparoscopic versus open transhiatal approach for adenocarcinoma of the esophagogastric junction: A systematic review and meta-analysis

BackgroundThe incidence of adenocarcinoma of the esophagogastric junction (AEG) is increasing worldwide. Laparoscopic transhiatal approach (LTH) has gained growing popularity in the treatment of AEG. However, its safety and efficacy need to be evaluated.MethodsOriginal studies comparing LTH with open transhiatal approach (OTH) were searched. Meta-analysis was performed using RevMan 5.3.ResultsNine studies involving 2149 patients were eligible. Compared with OTH, LTH was associated with longer operation time (mean difference [MD] = 31min, 95%CI [20,41], P < 0.001) while less blood loss (MD = −103ml [-135, −72], P < 0.001), and harvested similar number of lymph nodes (MD = 0.1 [-1.2, 1.4], P = 0.89). There were no differences in time to ambulation (MD = −0.79 days [-1.77, 0.20], P = 0.12) or time to first flatus (MD = −0.82 days [-1.76, 0.11], P = 0.08); however, LTH was associated with shorter postoperative hospital stay (MD = −1.70 days [-2.34, −1.05], P < 0.001). The mortality after surgery was comparable for LTH and OTH (risk difference [RD] = -0.00 [-0.01, 0.01], P = 0.55). The incidence of total major complications was similar in LTH (6.1%) and OTH (8.4%) (RD = −0.02 [-0.05, 0.01], P = 0.12); there were no significant differences in the incidence of each complication. Furthermore, LTH achieved similar 2-year overall survival (OS) rate (risk ratio [RR] = 1.17 [0.86, 1.60], P = 0.31) while higher 5-year OS rate (RR = 1.43 [1.18, 1.73], P = 0.0003) and significant improvement of OS (univariable hazard ratio = 0.65 [0.50, 0.84], P = 0.0009; multivariable hazard ratio = 0.59 [0.44, 0.80], P = 0.0006).ConclusionsLTH is feasible and safe for AEG, and may provide more favorable short-term outcomes and potential long-term survival benefit, which needs to be confirmed by randomized trials.     

Preoperative prediction of central lymph node metastasis in cN0T1/T2 papillary thyroid carcinoma: A nomogram based on clinical and ultrasound characteristics

BackgroundPreoperative status of central lymph nodes is a key determinant of the initial surgical extent for papillary thyroid carcinoma (PTC). We aimed to develop and validate a nomogram based on preoperative clinical characteristics and ultrasound features to predict central lymph node status in patients with clinically lymph node-negative (cN0) T1/T2 PTC.MethodsThis retrospective study included 729 patients with cN0T1/T2 PTC who were treated between January 2015 and March 2020. Based on the ratio of 6:4, 431 patients who underwent surgeries relatively earlier comprised the training set to develop the nomogram, while the other 298 who underwent surgeries relatively later comprised validation set to validate the performance of nomogram. Least absolute shrinkage and selection operator (LASSO) regression and multivariate logistic regression were used to identify predictors of central lymph node metastasis (CLNM). These variables were used to construct a nomogram for predicting the risk of CLNM. The predictive performance, discriminative ability, calibration, and clinical utility of the nomogram model were evaluated in both sets.ResultsA total of 313 (42.9%) PTC patients were identified with CLNM. On multivariate logistic regression analyses, malegender, younger age, larger maximum diameter, multifocality, capsular invasion, infiltrative margins, intra-nodular vascularity, and aspect ratio >1 were independent risk factors for CLNM. Nomogram integrating these 8 factors showed excellent discrimination in the training [area under the curve (AUC): 0.788] and validation (AUC: 0.829) sets, and obtained well-fitted calibration curves. The cut-off value of this nomogram was 0.410 (～245 points). Decision curve analysis confirmed the clinical utility of the nomogram.ConclusionThe CLNM-predicting nomogram can facilitate stratification of cN0T1/T2 PTC patients. Prophylactic central neck lymph node dissection can be considered for those with high nomogram scores.     

The effect of the American Joint Committee on Cancer eighth edition on breast cancer staging and prognostication

IntroductionBreast cancer staging has been developed to quantify prognosis and guide treatment. The American Joint Committee on Cancer eighth edition manual (AJCC8) departed from traditional anatomic staging by incorporating biological factors such as grade, hormone and HER2 receptor status into a novel prognostic staging model. The aim of this study was to externally validate AJCC8 prognostic staging.MethodsThis retrospective cohort investigated patients diagnosed between 2010 and 2013 at the McGill University Health Center. Patients were classified using both anatomic and prognostic staging systems according AJCC8. Overall survival analysis using a multivariate Cox-proportional hazard model was performed and model accuracy was evaluated using the Harrell concordance index (C-index) and Akaike Information Criterion (AIC).ResultsThe cohort included 1703 women. Anatomic and prognostic stage assignments displayed discrepancies for 46.2% of patients, where 38.8% were downstaged and 7.5% were upstaged with prognostic staging. Patients with anatomic stages IB, IIA, IIB, IIIA and IIIC had high rates of downstaging (64.6–96.5%), as opposed to anatomic stages IA and IIIB where 93.1% and 75.0% of patients stage remained unchanged, respectively. The prognostic stage displayed increased prognostic accuracy with respect to overall survival, where the C-index was significantly higher compared to anatomic staging (0.810 vs 0.799, p < 0.05). In addition, prognostic staging displayed an improved model fit with a lower AIC (983.9) compared to anatomic staging (995.2).ConclusionPrognostic and anatomic staging differ in their classification of patients, where prognostic staging displays improved accuracy, supporting its use in informing patient prognosis and guiding treatment decisions.     

Association between the novel classification of lung adenocarcinoma subtypes and EGFR/KRAS mutation status: A systematic literature review and pooled-data analysis

ObjectivesThis study aims to determine the association of EGFR/KRAS mutation status with histological subtypes of lung adenocarcinoma (LAC) based on the IASLC/ATS/ERS classification.MethodsPubmed and Cochrane databases were searched from January 2011 to June 2018 for studies that included patients with LAC who underwent surgical resection were classified according to the new IASLC/ATS/ERS classification. EGFR/KRAS status assessment was requireded. The primary outcome was determined by the odds ratio (OR) of the incidence of mutation status of certain of each histological subtype. The reference group consisted of EGFR/KRAS mutation negative patients.ResultsTwenty-seven eligible studies involving 9022 patients with mutation gene detection were included for analysis. Among them, 6717 (74.5%) patients were from the Asian region and, 2305 (25.5%) patients were from Non-Asian regions. The most prevalent subtype was acinar (34.7%), followed by papillary (22.9%), lepidic (18.9%), solid (13.6%), micropapillary (6.3%), and invasive mucinous adenocarcinoma (3.5%). EGFR mutations were more common in patients with resected lepidic predominant adenocarcinoma (OR,1.76; 95%CI, 1.38–2.24;p < 0.01) and were rarely found in solid predominant adenocarcinoma (OR,0.28; 95%CI, 0.23–0.34;p < 0.01) or IMA (OR,0.10; 95%CI, 0.06–0.14;p < 0.01). Conversely, KRAS mutations were characterized by IMA (OR,7.01; 95%CI, 5.11–9.62;p < 0.01), and were less frequently identified in lepidic (OR,0.58; 95%CI, 0.45–0.75;p < 0.01) and acinar (OR,0.65; 95%CI, 0.55–0.78;p < 0.01) predominant subtypes. Further analyses were performed in Asian and Non-Asian groups and the results were consistent.ConclusionsThe current study confirms that the IASLC/ATS/ERS classification is associated with driver gene alterations in resected LAC.