Association of the GNAS1 T393C polymorphism with tumor stage and survival in gastric cancer

AIM： To analyze the impact of the GNAS1 T393C polymorphism on prognosis and histopathology of gastric cancer. METHODS： Genomic DNA was extracted from paraffinembedded tissues of 122 patients with primary gastric carcinoma and from the blood of 820 healthy white individuals. Allelic discrimination was performed by quantitative real-time polymerase chain reaction. Genotyping was correlated with histopathologic parameters and with overall survival according to the Kaplan-Meier approach and with multivariate analysis by multiple stepwise regression. RESULTS： Thirty-nine （32%） patients displayed a CC genotype, 57 （46.7%） a CT genotype and 26 （21.3%） a TT genotype. The frequency of the C allele （fC） in the patient group was 0.55, which was not significantly different from that of healthy blood donors. The distribution was compatible with the Hardy-Weinberg equilibrium. Analysis of clinicopathological parameters did not show any significant correlation of the T393C genotype with gender （P = 0.50）, differentiation （P = 0.29）, pT-category （P = 0.19）, pN-category （P = 0.30）, pM-category （P = 0.25）, R-category （P = 0.95）, the classifications according to WHO （P = 0.34）, Lauren （P = 0.16）, Goseki （P = 1.00） and Ming （P =0.74）. Dichotomization between C＋ （CC＋CT） and C-genotypes （FI）, however, revealed significantly more advanced tumor stages （P = 0.023） and lower survival rates （P = 0.043） for C allele carriers. CONCLUSION： The present study provides strong evidence to suggest that the GNAS1 T393C allele carrier status influences tumor progression and survival in gastric cancer with higher tumor stages and a worse outcome for C allele carriers.

High plasma levels of COL10A1 are associated with advanced tumor stage in gastric cancer patients

BACKGROUND Gastric cancer(GC)remains an aggressive malignancy with a high rate of mortality,being the third leading cause of cancer-related death.More than one million newly diagnosed cases and 782685 deaths due to GC were reported in 2018.GC is characterized by limited effective treatment options and the lack of consistent biomarkers for the diagnosis and prognosis of these patients.The discovery of new biomarkers useful in the early diagnosis of GC is mandatory.AIM To evaluate the potential of COL10A1 as a circulating biomarker for the diagnosis and prognosis of gastric adenocarcinoma patients.METHODS Plasma and tissue obtained from 49 patients with gastric adenocarcinoma have been used in exploring the expression of COL10A1.Real-time PCR and western blot techniques were used to evaluate COL10A1 level in gastric tumor tissue compared to normal adjacent tissue.The circulating level of COL10A1 was also evaluated by ELISA in plasma of gastric adenocarcinoma patients.Survival analysis was made in order to evaluate the potential of COL10A1 as a biomarker for the diagnosis and prognosis of gastric adenocarcinoma patients.RESULTS Our results showed a significant increase in COL10A1 gene expression and protein levels in gastric tumor tissue compared to adjacent normal tissue(P<0.05).COL10A1 seems to show an elevated expression from the beginning of carcinogenesis,in the early stages,and its increased level remains elevated during cancer progression.A significant increase of COL10A1 plasma level in gastric adenocarcinoma patients was also identified.Moreover,increased COL10A1 plasma level was associated with poor survival of the patients.Plasma COL10A1 performed a diagnostic value in GC with area under the receiver operating characteristic curve(AUC)of 0.9171(P=0.0002),sensitivity of 87.76%,and specificity of 100.0%.Furthermore,this study demonstrated the potential role of plasma COL10A1 in the early detection of GC,as in the early stage,we obtained an AUC of 0.8789(P=0.0030),sensitivity of 81.25%,and specificity of 100.0%.CONCLUSION Circulating expression level of COL10A1 is significantly increased in gastric adenocarcinoma patients being associated with poor survival and is a potential biomarker for early detection of GC.

Correlation of tumor-associated macrophage density and proportion of M2 subtypes with the pathological stage of colorectal cancer

BACKGROUND Colorectal cancer(CRC)is a prevalent global malignancy with complex prognostic factors.Tumor-associated macrophages(TAMs)have shown paradoxical associations with CRC survival,particularly concerning the M2 subset.AIM We aimed to establish a simplified protocol for quantifying M2-like TAMs and explore their correlation with clinicopathological factors.METHODS A cross-sectional study included histopathological assessment of paraffinembedded tissue blocks obtained from 43 CRC patients.Using CD68 and CD163 immunohistochemistry,we quantified TAMs in tumor stroma and front,focusing on M2 proportion.Demographic,histopathological,and clinical parameters were collected.RESULTS TAM density was significantly higher at the tumor front,with the M2 proportion three times greater in both zones.The tumor front had a higher M2 proportion,which correlated significantly with advanced tumor stage(P=0.04),pathological nodal involvement(P=0.04),and lymphovascular invasion(LVI,P=0.01).However,no significant association was found between the M2 proportion in the tumor stroma and clinicopathological factors.CONCLUSION Our study introduces a simplified protocol for quantifying M2-like TAMs in CRC tissue samples.We demonstrated a significant correlation between an increased M2 proportion at the tumor front and advanced tumor stage,nodal involvement,and LVI.This suggests that M2-like TAMs might serve as potential indicators of disease progression in CRC,warranting further investigation and potential clinical application.

Survival analysis of children with stage Ⅱ testicular malignant germ cell tumors treated with surgery or surgery combined with adjuvant chemotherapy

For children with stage II testicular malignant germ cell tumors(MGCT), the survival is good with surgery and adjuvant chemotherapy. However, there is limited data on surgical results for cases in which there was no imaging or pathologic evidence of residual tumor, but in which serum tumor markers either increased or failed to normalize after an appropriate period of half-life time post-surgery. To determine the use of chemotherapy for children with stage II germ cell tumors, we analyzed the outcomes(relapse rate and overall survival) of patients who were treated at the Sun Yat-sen University Cancer Center between January 1990 and May 2013. Twenty-four pediatric patients with a median age of 20 months(range, 4 months to 17 years) were enrolled in this study. In 20 cases(83.3%), the tumors had yolk sac histology. For definitive treatment, 21 patients underwent surgery alone, and 3 patients received surgery and adjuvant chemotherapy. No relapse was observed in the 3 patients who received adjuvant chemotherapy, whereas relapse occurred in 16 of the 21 patients(76.2%) treated with surgery alone. There were a total of 2 deaths. Treatment was stopped for 1 patient, who died 3 months later due to the tumor. The other patient achieved complete response after salvage treatment, but developed lung and pelvic metastases 7 months later and died of the tumor after stopping treatment. For children treated with surgery alone and surgery combined with adjuvant chemotherapy, the 3-year event-free survival rates were 23.8% and 100%, respectively(P = 0.042), and the 3-year overall survival rates were 90.5% and 100%, respectively(P = 0.588). These results suggest that adjuvant chemotherapy can help to reduce the recurrence rate and increase the survival rate for patients with stage II germ cell tumors.

Detection of the <i>PIK3CA</i>Mutation in Circulating Tumor DNA as a Possible Predictive Indicator for Poor Prognosis of Early-Stage Breast Cancer

Objectives: Circulating tumor DNA (ctDNA) is shown to provide the real-time genomic information of metastatic breast cancer. This study elucidates the clinico-pathological significance of ctDNA in early-stage breast cancer using the PIK3CA mutation as an indicator. Materials and Methods: Twenty-seven primary breast cancers without metastasis were surgically resected and pathologically diagnosed at the University of Tokyo Hospital, Japan. Genomic DNA of primary tumor was extracted from formalin-fixed and paraffin-embedded specimens. ctDNA was extracted from fresh-frozen plasma from patients. The PIK3CA mutations at E542K, E545K and H1047R were examined by Sanger sequencing or droplet digital PCR in 27 tumors and pre- and post-surgery plasma. Results: The PIK3CA mutations were detected in 13 (48%) of 27 primary tumors. These mutations did not significantly correlate with specific clinico-pathological characteristics of tumors. When ctDNA was examined, 4 (33%) of 12 cases carrying the mutated PIK3CA showed the identical mutation in pre-surgery plasma and 2 (50%) of them showed the identical mutations in post-surgery plasma. Interestingly, in these 2 cases in pathological stages IIIA and IA, fractional abundance of the mutated PIK3CA alleles to the total alleles in pre-surgery ctDNA was around 1% or more and was higher than that of the other two cases without PIK3CA mutations in post-surgery ctDNA. Conclusions: The PIK3CA mutation in ctDNA is detectable even in a subset of early-stage breast cancer. Furthermore, fractional abundance of the mutated PIK3CA in pre-surgery ctDNA could provide a possible predictive indicator for tumor burden and for choosing the appropriate adjuvant treatment of breast cancer.

Immunohistochemical expression of matrix metalloproteinase-9 and 13 in oral squamous cell carcinoma and their role in predicting lymph node metastasis

BACKGROUND One of the main characteristics of oral squamous cell carcinoma(OSCC)is that it metastasizes to cervical lymph nodes frequently with a high degree of local invasiveness.A primary feature of malignant tumors is their penetration of neighboring tissues,such as lymphatic and blood arteries,due to the tumor cells'capacity to break down the extracellular matrix(ECM).Matrix metalloproteinases(MMPs)constitute a family of proteolytic enzymes that facilitate tissue remo-deling and the degradation of the ECM.MMP-9 and MMP-13 belong to the group of extracellular matrix degrading enzymes and their expression has been studied in OSCC because of their specific functions.MMP-13,a collagenase family member,is thought to play an essential role in the MMP activation cascade by breaking down the fibrillar collagens,whereas MMP-9 is thought to accelerate the growth of tumors.Elevated MMP-13 expression has been associated with tumor behavior and patient prognosis in a number of malignant cases.The authors wish to thank Jadhav KB for his valuable opinion during the preparation of the manuscript.

Clinical Utility of Tumor Markers

Tumor markers comprise a wide spectrum of biomacromolecules excessively synthesized by a variety of neoplastic cells. These markers can be endogenous products of highly active metabolites from malignant neoplastic cells or the products of newly activated genes. Ideally, tumor markers should be highly sensitive, specific, and reliable with a high prognostic value and organ specificity. In addition, they should reflect the tumor stage. However, no tumor markers identified thus far have all of these characteristics. Nevertheless, most tumor markers show excellent clinical relevance for monitoring the efficacy of a variety of therapies. We herein review how to use the recommended tumor markers to diagnose malignancies, such as gastrointestinal carcinoma, liver cancer, bile duct/pancreatic cancer, lung cancer, breast cancer, gynecologic cancer, and urologic cancer.

Radiomics approach for preoperative identification of stages Ⅰ-Ⅱand Ⅲ-Ⅳ of esophageal cancer

Objective： To predict preoperative staging using a radiomics approach based on computed tomography （CT）images of patients with esophageal squamous cell carcinoma （ESCC）.Methods： This retrospective study included 154 patients （primary cohort： n： t 14; validation cohort： n：40） withpathologically confirmed ESCC. All patients underwent a preoperative CT scan from the neck to abdomen. Highthroughput and quantitative radiomics features were extracted from the CT images for each patient. A radiomicssignature was constructed using the least absolute shrinkage and selection operator （Lasso）. Associations betweenradiomics signature, tumor volume and ESCC staging were explored. Diagnostic performance of radiomicsapproach and tumor volume for discriminating between stages Ⅰ-Ⅱand Ⅲ-Ⅳ was evaluated and compared usingthe receiver operating characteristics （ROC） curves and net reclassification improvement （NRI）.Results= A total of 9,790 radiomics features were extracted. Ten features were selected to build a radiomicssignature after feature dimension reduction. The radiomics signature was significantly associated with ESCCstaging （P〈0.001）, and yielded a better performance for discrimination of early and advanced stage ESCC comparedto tumor volume in both the primary [area under the receiver operating characteristic curve （AUC）： 0.795 vs. 0.694,P=0.003; NRI=0.424）] and validation cohorts （AUC： 0.762 vs. 0.624, P=0.035; NRI=0.834）.Conclusions： The quantitative approach has the potential to identify stage Ⅰ-Ⅱand Ⅲ-Ⅳ ESCC beforetreatment.

Transrectal ultrasound and magnetic resonance imaging measurement of extramural tumor spread in rectal cancer

AIM： To evaluate the agreement between transrectal ultrasound （TRUS） and magnetic resonance imaging （MRI） in classification of ≥ T3 rectal tumors. METHODS： From January 2010 to January 2012, 86 consecutive patients with ≥ T3 tumors were included in this study. The mean age of the patients was 66.4 years （range： 26-91 years）. The tumors were all ≥ T3 on TRUS. The sub-classification was defined by the penetration of the rectal wall： a： 0 to 1 mm; b： 1-5 mm, c： 6-15; d： 〉 15 mm. Early tumors as ab （≤ 5 ram） and advanced tumors as cd （〉 5 mm）. All patients underwent TRUS using a 6.5 MHz transrectal transducer. The MRI was performed with a 1.5 T Phil- ips unit. The TRUS findings were blinded to the radiol- ogist performing the interpretation of the MRI images and measuring the depth of extramural tumor spread RESULTS： TRUS found 51 patients to have an early ≥ T3 tumors and 35 to have an advanced tumor, where- as MRI categorized 48 as early ≥ T3 tumors and 38 as advanced tumors. No patients with tumors classified as advanced by TRUS were found to be early on MRI. The kappa value in classifying early versus advanced T3 rectal tumors was 0.93 （95% CI： 0.85-1.00）. We found a kappa value of 0.74 （95% CI： 0.63-0.86） for the total sub-classification between the two methods. The mean maximal tumor outgrowth measured by TRUS, 5.5 mm ± 5.63 mm and on MRI, 6.3 mm ±6.18 mm, P = 0.004. In 19 of the 86 patients the following CT scan or surgery revealed distant metastases; of the 51 patients in the ultrasound ab group three （5.9%） had metastases, whereas 16 （45.7%） of 35 in the cd group harbored distant metastases, P = 0.00002. The odds ratio of having distant metastases in the ultra- sound cd group compared to the ab group was 13.5 （95% CI： 3.5-51.6）, P = 0.00002. The mean maximal ultrasound measured outgrowth was 4.3 mm （95% CI： 3.2-5.5 mm） in patients without distant metastases, while the mean maximal outgrowth was 9.5 mm （95% CI： 6.2-12.8 ram） in the patients with metastases, P = 0.00004. Using the MRI classification three （6.3%） of 48 in the MRI ab group had distant metastases, while 16 （42.1%） of the 38 in the MRI cd group, P = 0.00004. The MRI odds ratio was 10.9 （95% CI： 2.9-41.4）, P = 0.00008. The mean maximal MRI measured out- growth was 4.9 mm （95% CI： 3.7-6.1 turn） in patients without distant metastases, while the mean maximal outgrowth was 11.5 mm （95% CI： 7.8-15.2 mm） in the patients with metastases, P = 0.000006. CONCLUSION： There is good agreement between TRUS and MRI in the pretreatment sub-classification of ≥ T3 tumors. Distant metastases are more frequent in the advanced group.

Pancreatic neuroendocrine neoplasms: Magnetic resonance imaging features according to grade and stage

AIMTo describe magnetic resonance (MR) imaging features of pancreatic neuroendocrine neoplasms (PanNENs) according to their grade and tumor-nodes-metastases stage by comparing them to histopathology and to determine the accuracy of MR imaging features in predicting their biological behavior.METHODSThis study was approved by our institutional review board; requirement for informed patient consent was waived due to the retrospective nature of the study. Preoperative MR examinations of 55 PanNEN patients (29 men, 26 women; mean age of 57.6 years, range 21-83 years) performed between June 2013 and December 2015 were reviewed. Qualitative and quantitative features were compared between tumor grades and stages determined by histopathological analysis.RESULTSIll defined margins were more common in G2-3 and stage III-IV PanNENs than in G1 and low-stage tumors (P < 0.001); this feature had high specificity in the identification of G2-3 and stage III-IV tumors (90.3% and 96%, 95%CI: 73.1-97.5 and 77.7-99.8). The mean apparent diffusion coefficient value was significantly lower in G2-3 and stage III-IV lesions compared to well differentiated and low-stage tumors (1.09 × 10-3 mm2/s vs 1.45 × 10-3 mm2/s and 1.10 × 10-3 mm2/s vs 1.53 × 10-3 mm2/s, P = 0.003 and 0.001). Receiving operator characteristic analysis determined optimal cut-offs of 1.21 and 1.28 × 10-3 mm2/s for the identification of G2-3 and stage III-IV tumors, with sensitivity and specificity values of 70.8/80.7% and 64.5/64% (95%CI: 48.7-86.6/60-92.7 and 45.4-80.2/42.6-81.3).CONCLUSIONMR features of PanNENs vary according to their grade of differentiation and their stage at diagnosis and could predict the biological behavior of these tumors.

Low-dose spectral insufflation computed tomography protocol preoperatively optimized for T stage esophageal cancer-preliminary research experience

AIM To evaluate the T stage of esophageal squamous cell carcinoma(ESCC) using preoperative low-dose esophageal insufflation computed tomography(EICT).METHODS One hundred and twenty ESCC patients confirmed by surgery or esophagoscopy were divided into three groups. Groups B and C were injected with 300 mgI/kg contrast medium for automatic spectral imaging assist(GSI assist), while group A underwent a conventional 120 kVp computed tomography(CT) scan with a 450 mg I/kg contrast medium injection. EICT was performed in group C. Group A was reconstructed with filtered back projection, and groups B and C were reconstructed with 50% adaptive statistical iterative reconstruction. The contrast-to-noise ratio of lesion-to-mediastinal adipose tissue and the radiation dose were measured. Specific imaging features were observed, and T stage ESCCs were evaluated.RESULTS The sensitivity and accuracy of the T1/2 stage were higher in group C than in groups A and B(sensitivity: 43.75% vs 31.82% and 33.33%; accuracy: 54.29% vs 46.67% and 52.50%, respectively). With regard to the T3 stage, the sensitivity and specificity in group C were higher than those in groups A and B(sensitivity: 56.25% vs 41.17% and 44.44%; specificity: 73.68% vs 67.86% and 63.64%, respectively). The diagnostic sensitivity, specificity and accuracy of the T4 stage were similar among all groups. There were no significant differences in volume CT dose index [(5.91 ± 2.57) mGy vs(3.24 ± 1.20) vs(3.65 ± 1.77) mGy], doselength product [(167.10 ± 99.08) mGy·cm vs(113.24 ± 54.46) mGy·cm vs(117.98 ± 32.32) mGy·cm] and effective dose [(2.52 ± 1.39) vs(1.63 ± 0.76) vs(1.73 ± 0.44) mSv] among the groups(P > 0.05). However, groups B and C received similar effective doses but lower iodine loads than group A [(300 vs 450) mgI/kg].CONCLUSION EICT combined with GSI assist allows differential diagnosis between the T1/2 and T3 stages. The ability to differentially diagnose the T3 and T4 stages of medullary ESCC can be improved by quantitatively and qualitatively analyzing the adipose tissue in front of the vertebral body.

Revisions to the Tumor,Node,Metastasis staging of lung cancer(8th edition):Rationale,radiologic findings and clinical implications

The Tumor, Node, Metastasis(TNM) staging system,adopted by the Union for International Cancer Control(UICC) and the American Joint Committee on Cancer(AJCC), has been recently revised, with the new 8^(th) edition of the staging manual being published in January 2017. This edition has few but important evidencebased changes to the TNM staging system used for lung cancer. Radiologists should be aware of the updated classification system to accurately provide staging information to oncologists and oncosurgeons. In this article, we discuss the rationale, illustrate the changes with relevance to Radiology, and review the clinical implications of the 8^(th) edition of the UICC/AJCC TNM staging system with regards to lung cancer.

Health-related quality of life evaluated by tumor node metastasis staging system in patients with hepatocellular carcinoma

AIM: To investigate and evaluate the change in healthrelated quality of life (HRQoL) by tumor node metastasis (TNM) staging system in patients with hepatocellular carcinoma (HCC). METHODS: A total of 140 patients diagnosed with HCC between June 2008 and April 2009 in our department were enrolled to this study. One hundred and thirty-five (96.5%) patients had liver cirrhosis secondary to hepatitis B virus (HBV) infection, 73 (54.07%) of them being HBV DNA positive; the other etiologies of liver cirrhosis were alcoholic liver disease (1.4%), hepatitis C (1.4%) or cryptogenic (0.7%). All subjects were fully aware of their diagnosis and provided informed consent. HRQoL was assessed before treatment using the functional assessment of cancer therapy-hepatobiliary (FACT-Hep) questionnaire. Descriptive statistics were used to evaluate demographics and disease-specific characteristics of the patients. One-way analysis of variance and independent samples t tests were used to compare the overall FACT-Hep scores and clinically distinct TNM stages. Scores for all FACT-Hep items were analyzed by frequency analyses. The mean scores obtained from the FACT-Hep in different Child-Pugh classes were also evaluated. RESULTS: The mean FACT-Hep scores were reduced significantly from TNM StageⅠto Stage Ⅱ, Stage ⅢA, Stage ⅢB group (687 ± 39.69 vs 547 ± 42.57 vs 387 ± 51.24 vs 177 ± 71.44, P = 0.001). Regarding the physical and emotional well-being subscales, scores decreased gradually from Stage Ⅰ to Stage ⅢB (P = 0.002 vs Stage Ⅰ; P = 0.032 vs Stage Ⅱ; P = 0.033 vs Stage ⅢA). Mean FACT-Hep scores varied by Child-Pugh class, especially in the subscales of physical well-being, functional well-being and the hepatobiliary cancer (P = 0.001 vs Stage I; P = 0.036 vs Stage Ⅱ; P = 0.032 vs Stage ⅢA). For the social and family well-being subscale, only Stage ⅢB scores were significantly lower as compared with Stage Ⅰ scores (P = 0.035). For the subscales of functional well-being and hepatobiliary cancer, there were significant differences for Stages ⅡΙ, ⅢA and ⅢB (P = 0.002vs StageⅠ). CONCLUSION: HRQoL of patients with HCC worsens gradually with progression of TNM stages. The most impaired subscales of HRQoL, as measured by FACT-Hep, were physical and emotional well-being.

Pancreatic Neuroendocrine Neoplasms: Correlation between MR Features and Pathological Tumor Grades

This study investigated the accuracy of MRI features in differentiating the pathological grades of pancreatic neuroendocrine neoplasms（PNENs）. A total of 31 PNENs patients were retrospectively evaluated, including 19 cases in grade 1, 5 in grade 2, and 7 in grade 3. Plain and contrastenhanced MRI was performed on all patients. MRI features including tumor size, margin, signal intensity, enhancement patterns, degenerative changes, duct dilatation and metastasis were analyzed. Chi square tests, Fisher＇s exact tests, one-way ANOVA and ROC analysis were conducted to assess the associations between MRI features and different tumor grades. It was found that patients with older age, tumors with higher TNM stage and without hormonal syndrome had higher grade of PNETs（all P〈0.05）. Tumor size, shape, margin and growth pattern, tumor pattern, pancreatic and bile duct dilatation and presence of lymphatic and distant metastasis as well as MR enhancement pattern and tumor-topancreas contrast during arterial phase were the key features differentiating tumors of all grades（all P〈0.05）. ROC analysis revealed that the tumor size with threshold of 2.8 cm, irregular shape, pancreatic duct dilatation and lymphadenopathy showed satisfactory sensitivity and specificity in distinguishing grade 3 from grade 1 and grade 2 tumors. Features of peripancreatic tissue or vascular invasion, and distant metastasis showed high specificity but relatively low sensitivity. In conclusion, larger size, poorlydefined margin, heterogeneous enhanced pattern during arterial phase, duct dilatation and the presence of metastases are common features of higher grade PNENs. Plain and contrast-enhanced MRI provides the ability to differentiate tumors with different pathological grades.

Sixth and seventh tumor-node-metastasis staging system compared in gastric cancer patients

AIM: To investigate the clinical relevance and prognosis regarding survival according to the changes of the tumor-node-metastasis(TNM) in gastric cancer patients. METHODS: We retrospectively studied 347 consecutive subjects who underwent surgery for gastric adenocarcinoma at the Division of General Surgery, Hospital of Busto Arsizio, Busto Arsizio, Italy between June 1998 and December 2009. Patients who underwent surgery without curative intent, patients with tumors of the gastric stump and patients with tumors involving the esophagus were excluded for survival analysis. Patients were staged according to the 6thand 7thedition TNM criteria; 5-year overall survival rates were investigated, and the event was defined as death from any cause. RESULTS: After exclusion, our study population included 241 resected patients with curative intent for gastric adenocarcinoma. The 5-year overall survival(5-year OS) rate of all the patients was 52.8%. Thediagnosed stage differed in 32% of 241 patients based on the TNM edition used for the diagnosis. The patients in stage Ⅱ according to the 6thedition who were reclassified as stage Ⅲ had significantly worse prognosis than patients classified as stage Ⅱ(5-year OS, 39% vs 71%). According to the 6thedition, 135 patients were classifed as T2, and 75% of these patients migrated to T3 and exhibited a significantly worse prognosis than those who remained T2, regardless of lymph node involvement(37% vs 71%). The new N1 patients exhibited a better prognosis than the previous N1 patients(67% vs 43%). CONCLUSION: 7thTNM allows new T2 and N1 patients to be selected with better prognosis, which leads to different staging. New stratification is important in multimodal therapy.

Associating liver partition and portal vein ligation for staged hepatectomy: From technical evolution to oncological benefit

Associating liver partition and portal vein ligation for staged hepatectomy(ALPPS) is a novel approach in liver surgery that allows for extensive resection of liver parenchyma by inducing a rapid hypertrophy of the future remnant liver. However,recent reports indicate that not all patients eligible for ALPPS will benefit from this procedure. Therefore,careful patient selection will be necessary to fully exploit possible benefits of ALPPS. Here,we provide a comprehensive overview of the technical evolution of ALPPS with a special emphasis on safety and oncologic efficacy. Furthermore,we review the contemporary literature regarding indication and benefits,but also limitations of ALPPS.

seventh tumor-node-metastasis staging of gastric cancer: Five-year follow-up

Seventh tumor-node-metastasis(TNM) classification for gastric cancer,published in 2010,introduced changes in all of its three parameters with the aim to increase its accuracy in prognostication. The aim of this review is to analyze the efficacy of these changes and their implication in clinical practice. We reviewed relevant Literature concerning staging systems in gastric cancer from 2010 up to March 2016. Adenocarcinoma of the esophago-gastric junction still remains a debated entity,due to its peculiar anatomical and histological situation: further improvement in its staging are required. Concerning distant metastases,positive peritoneal cytology has been adopted as a criterion to define metastatic disease: however,its search in clinical practice is still far from being routinely performed,as staging laparoscopy has not yet reached wide diffusion. Regarding definition of T and N: in the era of multimodal treatment these parameters should more influence both staging and surgery. The changes about T-staging suggested some modifications in clinical practice. Differently,many controversies on lymph node staging are still ongoing,with the proposal of alternative classification systems in order to minimize the extent of lymphadenectomy. The next TNM classification should take into account all of these aspects to improve its accuracy and the comparability of prognosis in patients from both Eastern and Western world.

Prognostic factors and survival after surgical resection of pancreatic neuroendocrine tumor with validation of established and modified staging systems

Background: Pancreatic neuroendocrine tumors(PNETs) display wide heterogeneity with highly variable prognosis. This study aimed to identify variables related to survival after surgical resection of PNET.Methods: A total of 143 patients were identified from a prospectively maintained database. Patient characteristics were analyzed and prognostic factors for overall survival and progression-free survival were evaluated. The WHO, ENETS and AJCC scoring systems were applied to the cohort, and their ability to predict patient outcomes were compared.Results: Multivariate analysis found that female gender, lymph node metastases and increasing WHO2010 grade to be independently associated with reduced overall survival(P < 0.05). Patients requiring multi-visceral resection or debulking surgery found to be associated with shortest survival. ROC analysis found the ENETS and AJCC scoring systems to be similarly predictive of 5-year overall survival. Modified Ki67 significantly improved its accuracy in predicting 5-year overall survival(AUROC: 0.699 vs 0.605;P < 0.01).Conclusions: Multi-visceral or debulking surgery is associated with poor outcomes. There seems to be no significant difference between enucleation and anatomical segmental resection. Available scoring systems have reasonable accuracy in stratifying disease severity, with no system identified as being superior.Prognostic stratification with modified grading systems needs further validation before applied in clinical practice.

Surgical procedure determination based on tumor-node-metastasis staging of gallbladder cancer

AIM: To investigate the impact of surgical procedures on prognosis of gallbladder cancer patients classified with the latest tumor-node-metastasis(TNM) staging system.METHODS: A retrospective study was performed by reviewing 152 patients with primary gallbladder carcinoma treated at Peking Union Medical College Hospital from January 2003 to June 2013. Postsurgical follow-up was performed by telephone and outpatient visits. Clinical records were reviewed and patients were grouped based on the new edition of TNM staging system(AJCC, seventh edition, 2010). Prognoses were analyzed and compared based on surgical operations including simple cholecystectomy, radical cholecystectomy(or extended radical cholecystectomy), and palliative surgery. Simple cholecystectomy is, by definition, resection of the gallbladder fossa. Radical cholecystectomy involves a wedge resection of the gallbladder fossa with 2 cm nonneoplastic liver tissue; resection of a suprapancreatic segment of the extrahepatic bile duct and extended portal lymph node dissection may also be considered based on the patient's circumstance. Palliative surgery refers to cholecystectomy with biliary drainage. Data analysis was performed with SPSS 19.0 software. KaplanMeier survival analysis and Logrank test were used for survival rate comparison. P < 0.05 was consideredstatistically significant.RESULTS: Patients were grouped based on the new 7th edition of TNM staging system, including 8 cases of stage 0, 10 cases of stage Ⅰ, 25 cases of stage Ⅱ, 21 cases of stage ⅢA, 21 cases of stage ⅢB, 24 cases of stage ⅣA, 43 cases of stage ⅣB. Simple cholecystectomy was performed on 28 cases, radical cholecystectomy or expanded gallbladder radical resection on 57 cases, and palliative resection on 28 cases. Thirty-nine cases were not operated. Patients with stages 0 and Ⅰ disease demonstrated no statistical significant difference in survival time between those receiving radical cholecystectomy and simple cholecystectomy(P = 0.826). The prognosis of stage Ⅱ patients with radical cholecystectomy was better than that of simple cholecystectomy. For stage Ⅲ patients, radical cholecystectomy was significantly superior to other surgical options(P < 0.05). For stage ⅣA patients, radical cholecystectomy was not better than palliative resection and non-surgical treatment. For stage ⅣB, patients who underwent palliative resection significantly outlived those with non-surgical treatment(P < 0.01)CONCLUSION: For stages 0 and Ⅰ patients, simple cholecystectomy is the optimal surgical procedure, while radical cholecystectomy should be actively operated for stages Ⅱ and Ⅲ patients.

DWI、DCE-MRI在中老年宫颈癌诊断、分期中的价值

目的探讨弥散加权序列(DWI)及动态增强磁共振成像(DCE-MRI)在宫颈癌诊断、分期中的价值。方法选取经病理证实的宫颈癌患者47例,行常规MR、扩散加权成像(DWI)扫描和动态对比增强磁共振(DCE-MR)扫描。按照FIGO分期分为两组,由两名有经验的影像医师勾画ROI,比较Ⅰ期+ⅡA期组与ⅡB及以上分期组组间不同定量参数之间的差异。结果1组平均ADC值为(0.869±0.181)×10^(-3)mm^(2)/s,2组为(0.716±0.1)×10^(-3)mm^(2)/s,差异有统计学意义(P<0.05)。1、2组K^(trans)、K_(ep)、V_(e)非参数检验结果示差异有统计学意义(P<0.05)。结论在常规MRI扫描基础上,应用DWI及DCE-MRI可以更全面、准确地对宫颈癌进行诊断和分期评估,对临床制定个性化的治疗方案具有重要的参考价值。