Grade G3 Research Articles

A Comparative Analysis of Clinical Characteristics and Histomorphologic and Immunohistochemical Spectrum of Gallbladder Carcinoma in Young Adults (< 45Years) and Elderly Adults (> 60Years).

Gallbladder carcinoma (GBC) is more frequent after 60years of age; its behavior in young adults has not been much studied. A retrospective analysis was performed in patients who underwent a cholecystectomy procedure between the years 2001 to 2016. A group of young patients (< 45) were compared with elderly patients (> 60years) with reference to various clinical, histomorphologic, and immunohistochemical parameters. Statistical analysis was performed using t test and Fisher's test. Survival curves were calculated by Kaplan-Meier actuarial survival curves and log-rank tests. One hundred and one patients with GBC were observed during the study period. Of these, 14 patients (13.9%) belonged to the study group (age range 20 to 45years) and 43 patients (42.6%) constituted the comparison elderly control group (age range 60 to 80years). Forty-four pts. were in the middle-aged group (46 to 59years) and were thus excluded from the study. With reference to age (< 45 and >60), no significant difference was found in sex (females 64.3% vs 69.8%, p = 0.7), presence of gall stones (64% vs 60%, p = 0.8), advanced disease at presentation (T4) (14.3% vs 7%, p = 0.40), incidental detection of gallbladder carcinoma (28.5% vs 28%, p = 0.9), tumor stage at presentation (stage I/II) (35.7% vs 49%, p = 0.39), and poor differentiation (tumor grades G3) (14% vs 12%, p = 0.79). Full-length involvement (28.5% vs 11.6%, p = 0.015) of the gallbladder and abundant tumor necrosis (43% vs 14%, p = 0.021) were more common in the younger patients group whereas adenosquamous and pure squamous cell carcinoma were predominantly observed in elderly patients. Immunohistochemical studies showed higher percentage of overexpression of p53 and Ki-67 proliferation indices in the younger population. Overall survival in younger patients was 48months whereas in elderly patients it was 36months. Histological markers denoting aggressive tumor behavior were observed in gallbladder carcinomas of younger individuals; further studies are needed to delineate the differences in molecular mechanisms involved in progression of the tumor in the two groups.

Low expression of A-kinase anchor protein 5 predicts poor prognosis in non-mucin producing stomach adenocarcinoma based on TCGA data.

In the past, there were not a lot of studies on how A-kinase anchor protein 5 (AKAP5) involving in the pathogenesis and prognosis of non-mucin producing stomach adenocarcinoma (NMSA). Therefore, we studied the relationship between AKAP5 and the prognosis of NMSA and its possible mechanisms using publicly available data from The Cancer Genome Atlas (TCGA). RNA high-throughput sequencing and clinicopathologic data of NMSA were downloaded from the TCGA. Clinical pathologic features associated with AKAP5 expression were analyzed using the chi-square and Fisher exact tests. The relationship between the overall survival (OS) and AKAP5 expression was analyzed by the Kaplan-Meier method and the Cox regression analysis. GSEA analysis was performed using the TCGA dataset. Our results indicated that the AKAP5 expression was increased in NMSA (all tumor vs. adjacent mucosa). Also, histologic grade, clinical stage, N classification, and survival status were significantly correlated with AKAP5 expression. Kaplan-Meier curves showed that low AKAP5 expression was associated with a poor OS among the NMSA patients (P=5.003e-05), and in the clinical stage III and IV (P=4.646e-05), TNM stage T3 (P=0.016), T4 (P=0.001), N2 (P=0.012), N3 (P=0.003), M0 (P=3.911e-05), and histological grade G3 (P=1.658e-04) subgroups. Cox regression analysis showed that reduced AKAP5 expression in NMSA is associated with age (HR =1.03, P=0.007), stage (HR =1.84 for stage I, II vs. stage III, IV, P=0.002) and M classification (HR =1.8 for M0 vs. M1, P=0.010). Gene sets related to cholesterol homeostasis, glycolysis, estrogen response late, adipogenesis, estrogen response early, notch signaling, and peroxisome were differentially enriched with the low AKAP5 expression phenotype. Low expression of AKAP5 may be a potential molecular marker for predicting poor prognosis of NMSA. Besides, cholesterol homeostasis, glycolysis, estrogen response, adipogenesis, notch signaling, and peroxisome may be the key pathways regulated by AKAP5 in NMSA. It also suggested that AKAP5 might potentially have biological functions in the development of stomach adenocarcinoma.

Clinicopathologic features and prognostic analysis of 240 patients with gastric neuroendocrine neoplasms

Objective: To investigate clinicopathological features and prognostic factors of gastric neuroendocrine tumors (G-NEN). Methods: Clinical and pathological data of patients with G-NEN diagnosed by pathological examination in Chinese PLA General Hospital from January 2000 to June 2018 were retrospectively analyzed in this case-control study. Patients with complicated visceral lesions, other visceral primary tumors, mental disorders and incomplete clinicopathological data were excluded. Finally, 240 hospitalized patients who met the inclusion criteria were enrolled. Physical examination information, tumor characteristics and pathological characteristics of patients were summarized. The Cox regression models were used to analyze the risk factors affecting G-NEN and the survival conditions were described by Kaplan-Meier survival curves and log-rank test. Results: In 240 patients with G-NEN, the mean age was (60.3±10.1) years; 181 were male (75.4%) and 59 females (24.6%); mean tumor diameter was (4.2±2.8) cm; 51 cases (21.2%) were neuroendocrine tumor (NET), 139 cases (57.9%) neuroendocrine carcinoma (NEC), 50 cases (20.8%) mixed neuroendocrine carcinoma (MANEC); 28 cases (11.7%) were G1 low grades, 34 cases (14.2%) G2 medium grades, and 178 cases (74.2%) G3 high grades; tumor infiltration depth T1 to T4 were 44 cases (18.3%), 27 cases (11.2%), 60 cases (25.0%) and 109 cases (45.4%) respectively; 163 cases (67.9%) developed lymphatic metastasis and 46 patients (19.2%) distant metastasis; tumor stage from stage I to stage IV were 55 cases (22.9%), 42 cases (17.5%), 94 cases (39.2%) and 53 cases (22.1%) respectively. Of the 240 G-NEN patients, 223 cases (92.9%) were followed up. The median survival time of the patients was 39.2 (95% CI: 29.1 to 47.5) months. Univariate survival analysis showed that age ≥ 60 years, tumor diameter ≥ 4.2 cm, tumor grade G3, lymphatic metastasis, distant metastasis, and tumor stage III-IV were risk factors for G-NEN patients. Multivariate survival analysis revealed that lymphatic metastasis (HR=1.783, 95%CI: 1.007-3.155, P=0.047) and distant metastasis (HR=2.288, 95% CI: 1.307-4.008, P=0.004) were independent risk factors of the prognosis. Further analysis of the G3 subgroup of G-NEN showed that the 5-year survival rate of NET-G3 was 76.19%, which was significantly higher than that of NEC-G3 and MANEC-G3 (15.60% and 24.73%, P=0.012). Conclusions: Most G-NEN patients are in advanced stage at diagnosis. Lymphatic metastasis and distant metastasis indicate poor prognosis. The prognosis of high proliferation NET-G3 patients is better as compared to those of NEC-G3 and MANEC-G3. This classification is worth further attention.

Evaluation of the expression of somatostatin receptors by immunohistochemistry in neuroendocrine tumors of the small intestine.

Most neuroendocrine neoplasms (NEN) are characterized by thepresence ofsomatostatin receptors (SSTR) which we use in location diagnostics and treatment. Theaim ofthis study was to evaluate theexpression ofsomatostatin receptors by immunohistochemistry in tissue obtained after surgery oftheprimary focus in thesmall intestine. The group ofpatients consisted of41 people, in 18 cases theprimary tumor was in thejejunum and in 23 in theileum. Theimmunohistochemical method was used to visualize thereceptors, using polyclonal antibodies in atwo-stage peroxidase method. In patients with NEN ofthesmall intestine, theSSTR2a and SSTR5 receptors are most commonly expressed, followed by SSTR2b and 3. In statistical analysis, it was shown that theexpression ofsomatostatin receptors was not dependent on theprimary site ofthetumor (p>0.05). Thedependence ofSSTR expression on histological maturity is evident. SSTR1, SSTR2b, SSTR3 and SSTR5 are more common in tumors with grading G1 (p<0.05). In thestudy group, theexception was SSTR2a, whose incidence was comparable in both groups (p=0.35). In NEN ofthesmall intestine, theexpression SSTR2a and SSTR5 is themost common.

Parameters for Predicting Tumour Response Following Neoadjuvant Chemoradiotherapy for Patients with Rectal Cancer.

Introduction: Pathologic response following neoadjuvant chemoradiotherapy (nCRT) can vary from pathologic complete response (pCR), to tumour downstaging or minimum to no response. Our goal was to evaluate the parameters that could predict response to neoadjuvant therapy for patients with rectal cancer. Method: We performed a retrospective study and reviewed the medical documentation for patients that received treatment for rectal cancer in our surgical department between 2014-2018 and received nCRT. Results: A total of 98 patients were included in the study. 66 patients were males (67,3%) and 32 were females (32,7%). The mean age was 64,6 (39-87). The 48 months overall survival rate was 81,63% and the 48 months disease-free survival rate was 69,38%. Tumour grading was considered as a statisti cally significant parameter for evaluating the pathologic response. The tumours most likely to respond to radio-chemotherapy were G1 or G2 grade. T4 tumours compared with lesser T stages were less likely to achieve pathologic complete response. Elevated CEA levels predicted a poor pathologic response to nCRT. Conclusion: Our study concluded that tumour related factors, biologic and imagistic findings such as tumour stage, lymph node, tumour differentiation grade and CEA levels can be used as parameters for predicting the tumour response following neoadjuvant therapy.

Quantitative Anti-HBc in Liver Pathological States in Patients with Chronic Hepatitis B Virus Infection.

Background Changes of hepatitis B core antigen antibody (anti-HBc) in liver pathological involvement in patients with chronic hepatitis B virus (HBV) infection have not been investigated in detail. This study aimed to explore evolving patterns of anti-HBc following liver pathological states and to investigate validities of anti-HBc for predicting liver pathological states. Methods 254 HBeAg-positive and 237 HBeAg-negative patients with chronic HBV infection were enrolled. Liver pathological diagnoses referred to Scheuer standard, and anti-HBc was measured using chemiluminescence microparticle immunoassay. Results Anti-HBc was significantly positively correlated with pathological grades and stages in both HBeAg-positive (rs = 0.312, P < 0.0001, and rs = 0.268, P < 0.0001) and HBeAg-negative (rs = 0.270, P < 0.0001, and rs = 0.147, P=0.0237) patients. The medians of anti-HBc in pathological grades of G1, G2, and G3 and stages of S1, S2, S3, and S4 in HBeAg-positive patients were all significantly lower than those in HBeAg-negative patients (all P < 0.005). The areas under receiver-operating characteristic curves (95% confidence interval) of anti-HBc for predicting pathological grades ≥G2 and ≥G3, and stages ≥S2 and =S4 in HBeAg-positive patients were 0.683 (0.622–0.740) and 0.662 (0.601–0.720), and 0.627 (0.564–0.687) and 0.683 (0.622–0.740), respectively, and in HBeAg-negative patients were 0.681 (0.618–0.740) and 0.702 (0.639–0.760), and 0.569 (0.503–0.633) and 0.630 (0.565–0.691), respectively. Conclusion Following hepatic aggravation of necroinflammation and progression of fibrosis, anti-HBc increases gradually in HBeAg-positive patients and continues to increase gradually in HBeAg-negative patients, which is a useful but unsatisfactory marker for monitoring pathological states.

Activity and safety of temozolomide in advanced adrenocortical carcinoma patients.

Temozolomide has shown a significant anti-proliferative activity on adrenocortical cancer (ACC) cells in vitro. On the basis of these results the drug was prescribed as second/third line in advanced metastatic ACC patients in four referral centers in Italy. We retrospectively collected anagraphic, clinical and pathological data of patients with advanced ACC with disease progression to standard chemotherapy plus mitotane who were treated with temozolomide at the dose of 200 mg/m2/die given for 5 consecutive days every 28 days. The primary endpoint was the disease control rate, defined as objective response or disease stabilization after 3 months. Secondary endpoints were overall survival (OS), progression-free survival (PFS) and drug safety. Twenty-eight patients have been included in the study. Ten patients (35.8%, 95% CI: 17.8-53.8) obtained a disease control from temozolomide treatment. In particular, 1 patient had a complete response, 5 patients a partial response and 4 patients stable disease. Median PFS was 3.5 months and median OS was 7.2 months. Disease response was more frequently observed in patients with methylation of O6-methylguanine-DNA methyltransferase (MGMT) gene. Temozolomide therapy was well tolerated and most toxicities were limited to grade G1-2 according to WHO criteria. Temozolomide was found active in the management of advanced ACC patients. The disease control rate obtained, however, was short-lived and the prognosis of treated patients was poor.

NAMPT, GRN, and SERPINE1 signature as predictor of disease progression and survival in gliomas.

Adipose tissue is an important source of adipokines involved in anti- and pro-inflammatory effects. Their involvement in certain cancers such as breast and colon cancer is known but in gliomas it remains unexplored till date. The aim of this study was to assess the status of adipokines as prognostic markers of gliomas (low grade gliomas [LGG] and glioblastoma mutiforme [GBM]). Expression status (messenger RNA [mRNA]), overall survival (OS) and disease-free survival (DFS) was identified using gene expression profiling interactive analysis server. Clinicopathological analysis and correlation between different adipokines was performed using Xena server. Protein expression status was analyzed using tissue sections from the Human Protein Atlas. Out of 11 adipokines studied visfatin (NAMPT), apelin (APLN), granulin (GRN), serpin peptidase inhibitor/plasminogen activator inhibitor type 1 (PAI-1) member 1 (SERPINE1), and chemokine (C-C motif) ligand 2 (CCL2) mRNA levels were significantly upregulated in both LGG and GBM. Interleukin 6 (IL6) mRNA was found be significantly upregulated only in GBM. NAMPT, GRN, SERPINE1, and IL6 showed reduced OS as well as worst DFS for patients having higher mRNA expression in LGG. Increased expression of CCL2 showed worst OS in LGG patients while resistin (RETN) and GRN showed the worst OS in GBM patients. Higher expression of RETN, GRN, IL6, SERPINE1, and CCL2 were found to be positively correlated with shorter DFS in GBM. In the clinicopathological analysis, NAMPT, GRN, IL6, SERPINE1, and CCL2 expressions were significantly associated between the neoplasm histological G2 and G3 grades. Furthermore, expression of NAMPT, GRN, tumor necrosis factor, IL6, SERPINE1, and CCL2 were significantly associated with histological type in LGG patients. NAMPT, GRN, SERPINE1, CCL2, and RETN expression were found to be correlated with each other in gliomas. Finally, NAMPT, GRN, and SERPINE1 were also found to be upregulated using immunohistochemistry in a lower grade and high grade gliomas as compared to normal cells. In conclusion, we have identified key adipokines, namely NAMPT, GRN, and SERPINE1 as potential diagnostic and prognostic markers that might be instrumental in the development and progression of gliomas.

Endoscopic management of 345 small rectal neuroendocrine tumours: A national study from the French group of endocrine tumours (GTE)

Small rectal neuroendocrine tumours are good candidates for endoscopic resection provided that complete pathological resection (R0) is obtained and their risk of metastatic progression is low. We conducted a large multicentre nationwide study to evaluate the outcomes of the management of non-metastatic rectal neuroendocrine tumours ≤2 cm diagnosed endoscopically. The medical records, the endoscopic and pathological findings of patients with non-metastatic rectal neuroendocrine tumours ≤2 cm managed from January 2000-June 2018 in 16 French hospitals, were retrospectively analysed. The primary objective was to describe the proportion of R0 endoscopic resections. A total of 329 patients with 345 rectal neuroendocrine tumours were included, 330 (96%) tumours were managed by local treatments: 287 by endoscopy only and 43 by endoscopy followed by transanal endoscopic microsurgery. The final endoscopic R0 rate was 134/345 (39%), which improved from the first endoscopy (54/225, 24%), to the second (60/100, 60%) and the third endoscopy (20/26, 77%). R0 was associated with endoscopic technique (90% for advanced techniques, 40% for mucosectomy and 17% for polypectomy), but not with tumour or patient characteristics. Twenty patients had metastatic disease, which was associated with tumour size ≥10 mm (odds ratio: 9.1, 95% confidence interval (3.5-23.5)), tumour grade G2-G3 (odds ratio: 4.2, (1.5-11.7)), the presence of muscular (odds ratio: ∞, (11.9-∞)) and lymphovascular invasion (odds ratio: 57.2, (5.6-578.9)). The resection of small rectal neuroendocrine tumours often requires multiple procedures. Training of endoscopists is necessary in order to better recognise these tumours and to perform the appropriate resection technique.

Disseminated Well-Differentiated Gastro-Entero-Pancreatic Tumors Are Associated with Metabolic Syndrome.

The association of well-differentiated gastro-entero-pancreatic neuroendocrine tumors (WD GEP-NETs) with metabolic syndrome (MetS), abdominal obesity, and fasting glucose abnormalities was recently described. The aim of this study was to evaluate whether the presence of MetS or any MetS individual component was also influenced by GEP-NET characteristics at diagnosis. A cohort of patients with WD GEP-NETs (n = 134), classified according to primary tumor location (gastrointestinal or pancreatic), pathological grading (G1 (Ki67 ≤ 2%) and G2 (>3 ≤ 20%) (WHO 2010), disease extension (localized, loco-regional, and metastatic), and presence of hormonal secretion syndrome (functioning/non-functioning), was evaluated for the presence of MetS criteria. After adjustment for age and gender, the odds of having MetS was significantly higher for patients with WD GEP-NET grade G1 (OR 4.35 95%CI 1.30–14.53) and disseminated disease (OR 4.52 95%CI 1.44–14.15). GEP-NET primary tumor location or secretory syndrome did not influence the risk for MetS. None of the tumor characteristics evaluated were associated with body mass index, fasting plasma glucose category, or any of the individual MetS components. Patients with GEP-NET and MetS depicted a higher risk of presenting a lower tumor grade and disseminated disease. The positive association between MetS and GEP-NET characteristics further highlights the potential link between the two conditions.

Late toxicities of prostate cancer radiotherapy with and without hydrogel SpaceAOR insertion.

To investigate whether the implantation of a hydrogel spacer (SpaceOAR) reduces long-term rectal toxicity for prostate cancer patients treated with intensity-modulated radiotherapy (IMRT). Patients with localised prostate cancer treated with 81Gy in 45fx of IMRT over 9weeks were retrospectively compared: 65 patients with SpaceOAR and 56 patients without SpaceOAR. Planning aims restricted rectal doses to V40 Gy<35%, V65 Gy<17%, V75 Gy<10%. Toxicities were evaluated between 3months and 3years after the completion of radiotherapy and were based on the common terminology criteria for adverse events (CTCAE) assessment tool for diarrhoea, haemorrhoids, faecal incontinence and proctitis. The cumulative incidence of low-grade diarrhoea (G1) was significantly higher in the non-SpaceOAR group (21.4% vs 6.2%; P=0.016). The cumulative incidence of proctitis (grades G1 and G2) was also higher in the non-SpaceOAR group (26.7% vs 9.2%; P=0.015); the cumulative incidence of G2 proctitis was higher in the latter group (P=0.043). There were no differences between the treatment groups for cumulative incidences of faecal incontinence and/or haemorrhoids. Three years after IMRT, diarrhoea and proctitis were higher in the non-SpaceOAR group, without reaching statistical significance. This finding was unchanged after correcting for baseline symptoms. SpaceOAR is of benefit in reducing the cumulative incidence of low-grade diarrhoea and proctitis for up to 3years after intensity-modulated radiotherapy.

Loss of CHEK2 Predicts Progression in Stage pT1 Non-Muscle-Invasive Bladder Cancer (NMIBC).

Downregulation of checkpoint protein kinase 2 (CHEK2), which is involved in DNA repair, is associated with poorer outcome in various tumors. Little is known about the role of CHEK2 in urothelial carcinoma of the bladder (UCB). In the present study, we investigated the prognostic impact of CHEK2 protein expression in stage pT1 UCB. This retrospective, single-center analysis was carried out in a cohort of patients initially diagnosed with a pT1 UCB between 2007 and 2015. Immunohistochemical (IHC) staining of CHEK2 was performed. CHEK2 expression was correlated with recurrence-free survival (RFS), progression-free survival (PFS), and cancer-specific survival (CSS) using Kaplan-Meier analysis and multivariable Cox regression analysis. The analysis included 126 patients (86% male, median age 71years). Loss of immunohistochemical protein expression of CHEK2 (<10%) was associated with significantly worse PFS (p = 0.041). Likewise, CHEK2 loss identified a subgroup of patients with worse PFS in the high-risk groups with concomitant CIS (p = 0.044), multifocal tumors (p < 0.001) and tumor grading G3 according to WHO1973 (p = 0.009). Multivariable Cox regression analysis revealed both loss of CHEK2 expression (HR: 4.18, 95%-CI: 1.35-12.93; p = 0.013) and multifocal tumors (HR: 4.53, 95%-CI:1.29-15.92; p = 0.018) as the only predictive factors for progression. Loss of IHC expression of CHEK2 in pT1 UCB is an independent predictor for progression to muscle-invasive disease and is also associated with worse PFS. This could help to identify high-risk patients who would benefit from early cystectomy.

Value of 68Ga-DOTANOC PET/CT imaging in primary diagnosis and staging of pancreatic neuroendocrine neoplasms

Objective To evaluate the value of 68Ga-1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid-1-Nal3-octreotide (DOTANOC) PET/CT imaging in the diagnosis and staging of pancreatic neuroendocrine neoplasms (pNENs). Methods Data of 48 patients (18 males, 30 females, age: 23-86 (50.0±14.7) years) who underwent 68Ga-DOTANOC PET/CT imaging from June 2016 to June 2018 were retrospectively analyzed. The histopathological results were considered as the gold standard. The diagnostic efficacies of 68Ga-DOTANOC PET/CT imaging and conventional imaging (CI) for pNENs were analyzed and compared (McNemar test). Imaging characteristics of true positive lesions in 68Ga-DOTANOC PET/CT imaging were analyzed. The maximum standardized uptake value (SUVmax) in different pathological grades of pNENs lesions were compared (Kruskal-Wallis rank sum test). Accuracy for TNM staging by 68Ga-DOTANOC PET/CT imaging and the correlations between the staging results and clinical TNM stages were analyzed (R×C contingency table). Results (1) The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of 68Ga-DOTANOC PET/CT imaging were 93.8%(30/32), 14/16, 93.8%(30/32), 14/16 and 91.7%(44/48). All true positive lesions detected by PET/CT showed focal uptake of 68Ga-DOTANOC with SUVmax of 30.52±23.57. There were 26 patients with confirmed pathological grades of G1 (n=10; SUVmax: 28.20 (17.60, 49.22)), G2 (n=13; SUVmax: 27.60 (13.05, 56.08)) and G3 (n=3; SUVmax: 13.68(10.02, 27.80)), with no significant difference in SUVmax among 3 groups (H=0.495, P>0.05). (2)Of the 48 patients, 95.8%(46/48) also underwent CI concurrent with PET/CT. The sensitivity, specificity, PPV, NPV and accuracy of CI were 60.0%(18/30), 9/16, 72.0%(18/25), 9/21 and 58.7%(27/46). The diagnostic efficacy of 68Ga-DOTANOC PET/CT imaging was significantly higher than that of CI (P=0.041). (3)The accuracies of 68Ga-DOTANOC PET/CT imaging for T, N, M staging were 93.3%(28/30), 6/6, 9/10, respectively, and the staging results were significantly correlated with clinical TNM stages (r=0.880, P<0.05). Conclusion 68Ga-DOTANOC PET/CT imaging has great values in the diagnosis and staging of pNENs. Key words: Pancreatic neoplasms; Neuroendocrine tumors; Octreotide; Gallium radioisotopes; Positron-emission tomography; Tomography, X-ray computed

A rational approach to postoperative surveillance for resected non-functional pancreatic neuro-endocrine tumours

BackgroundNon-functional pancreatic neuroendocrine tumours (NF-PNETs) are rare and have highly variable outcomes. Current guidelines recommend surveillance for NF-PNETs <2 cm. Patients who ultimately have surgical resection are at risk of disease recurrence, and data to support postoperative surveillance protocols are lacking. The aims of this study were to i) identify post-operative predictors of recurrence and ii) risk stratify patients at risk of recurrence. MethodsConsecutive patients who underwent surgery for NF-PNETs between 2002 and 2015 were identified retrospectively. Data were collected on demographics, pre-operative laboratory results and histopathological tumour characteristics. Statistical analyses were based on penalised Cox-regression modelling and a decision-tree model. Comparison of the variables identified was performed using ROC curves to identify the most sensitive and specific variable associated with disease recurrence. ResultsWe identified 73 patients (38 males) with a median age of 61.5 years (range: 31–79). The median period of follow-up was 49 months (5–131). During follow up, 10 deaths (13.9%) were recorded and disease recurrence occurred in 12 patients (16.4%). The Kaplan-Meier predicted 1-,3- and 5-year recurrence–free survival rates were 98.6% (95% CI = 95.9, 100%), 85.4% (76.9–94.8%) and 72% (58.7–88.2%) respectively. Cox multivariate analysis identified poor tumour differentiation (WHO G3 grade) and lymph node ratio (LNR) as independent predictors for recurrence (p < 0.05). A simple criterion of ‘tumour grade G3 or LNR ≥0.1’ was found to be sensitive and specific in detecting disease recurrence. ConclusionOur results have identified a simple and sensitive criterion for risk stratifying post-resection surveillance. Prospective validation in larger patient cohort is now warranted.

Identification of a 3-mRNA signature as a novel potential prognostic biomarker in patients with ovarian serous cystadenocarcinoma in G2 and G3.

The use of mRNAs as biomarkers serves to diagnose, treat, as well as aid the prognosis of cancer. The present study involved an analysis of mRNAs in the cell cycle at the G2 and G3 tumor grades for the prognosis of ovarian serous cystadenocarcinoma (OSC) using 364 clinical samples (G2:G3=42:322). Statistics aided the identification of NPFFR2, XPNPEP2 and CELA3B; the 3-mRNA model that allows for classification of patients into high- and low-risk groups using a median value of 0.9580745. The rates of survival varied (P=0.00149) and the independent detection of stratification of the risk of this disease was validated with success using the 3-mRNA signature, which was demonstrated to be more successful than the weight model. This approach was revealed to provide the prognosis of grade G2 and G3 in patients with OSC compared with factors used traditionally. Compared with traditional factors, this 3-mRNA model was demonstrated to be the only and independent prognostic factor for patients with G2 and G3 stage OSC. A literature survey was also performed in the present study in order to assess the role of the 3 genes and indirectly prove their effectiveness. The establishment of this new genetic model will enhance prospective prognosis and treatment for patients with OSC.

Reappraisal of a 2-Cm Cut-off Size for the Management of Cystic Pancreatic Neuroendocrine Neoplasms: A Multicenter International Study.

The aim of this study was to characterize an international cohort of resected cystic pancreatic neuroendocrine neoplasms (cPanNENs) and identify preoperative predictors of aggressive behavior. The characteristics of cPanNENs are unknown and their clinical management remains unclear. An observational strategy for asymptomatic cPanNENs ≤2 cm has been proposed by recent guidelines, but evidence is scarce and limited to single-institutional series. Resected cPanNENs (1995-2017) from 16 institutions worldwide were included. Solid lesions (>50% solid component), functional tumors, and MEN-1 patients were excluded. Aggressiveness was defined as lymph node (LN) involvement, G3 grading, distant metastases, and/or recurrence. Overall, 263 resected cPanNENs were included, among which 177 (63.5%) were >2 cm preoperatively. A preoperative diagnosis of cPanNEN was established in 162 cases (61.6%) and was more frequent when patients underwent endoscopic ultrasound [EUS, odds ratio (OR) 2.69, 95% confidence interval (CI) 1.52-4.77] and somatostatin-receptor imaging (OR 3.681, 95% CI 1.809-7.490), and for those managed in specialized institutions (OR 3.12, 95% CI 1.57-6.21). Forty-one cPanNENs (15.6%) were considered aggressive. In the whole cohort, LN involvement on imaging, age >65 years, preoperative size >2 cm, and pancreatic duct dilation were independently associated with aggressive behavior. In asymptomatic patients, older age and a preoperative size >2 cm remained independently associated with aggressiveness. Only 1 of 61 asymptomatic cPanNENs ≤2 cm displayed an aggressive behavior. The diagnostic accuracy of cPanNENs is increased by the use of EUS and somatostatin-receptor imaging and is higher in specialized institutions. Preoperative size >2 cm is independently associated with aggressive behavior. Consequently, a watch-and-wait policy for sporadic asymptomatic cPanNENs ≤2 cm seems justified and safe for most patients.

Injection in Facet Joint Arthropathy

Background: Facet syndrome is an articular disorder related to the lumbar facet joints and their innervations, and produces both local and radiating pain. Objective: The purpose of this study was to evaluate the outcome of steroid injection in treatment of facet joint arthropathy. Patient and Methods: This study was held on 23 patients suffered from chronic low back pain due to facet arthropathy at Al-Azhar University and Alharam Specialized Hospitals. There were 11 males and 12 females with mean age 46.27 years (28 to 60 years). History, clinical examination, x-ray, MRIs were done to all patients. Results: Pain was evaluated by VAS. The mean VAS pre injection was 8.1 ± 0.83 ranging from 6:10. Immediately post injection, the mean was decreased to 3.7 ± 0.85 ranging from 2:5. Six weeks after injection the mean was decreased to 3.6 ± 0.98 ranging from 2:5. Twelve weeks after injection the mean was elevated to 5.3 ± 0.91 ranging from 4 to 6. The mean ODI improved from 36.5 ± 6.9 to 21.1 ± 4.2 three months post injection. Conclusion: intra-articular facet joint injection is crucial in the diagnosis and treatment of facet joint syndrome. It is an easy to perform and effective treatment for temporary pain relief. The pain relief is sustained longer in patients with grade G2 and G3 of facet joints

Role of clinical and morphological data in prediction of regional lymph node involvement in early-stage breast cancer

Objective:to evaluate the frequency of axillary lymph node metastasis (detected at routine pathomorphological examination) in order to determine the group of patients who do not require lymph node surgery.Materials and methods.We analyzed medical records of 485 patients with breast cancer and no signs (either clinical or instrumental) of regional lymph node involvement who underwent surgery at the first stage of their treatment.Results and conclusion.In patients with cN0 cancer, only the size of primary tumor ≤1 cm was found to be a significant factor indicating that regional lymph nodes are not involved (in addition to palpation, ultrasound, mammography, and spiral x-ray computed tomography of the chest). In patients with сТ1c cancer, the majority of standard immunohistochemical markers cannot yet be used as predictors of regional lymph node involvement. However, tumor differentiation grade G1 is rather an exclusion, which in combination with the size of the primary tumor сТ1c can also be considered as a significant prognostic factor.

Spatio-temporal image correlation (STIC) in evaluation of advanced neuroendocrine tumours.

4D Ultrasound technology merging the Power Doppler option called High-Definition Flow (HDF) with Spatio-Temporal Image Correlation (STIC) is used in gynaecology and obstetrics. It seems to be a promising tool in assessing tissue vascularisation. The aim of the paper was to assess whether HDF STIC technique could be a useful tool for the evaluation of gastro-entero-pancreatic neuroendocrine neoplasm (GEP-NEN) advancement. Forty-eight patients [mean age 57.7 ± 10.3 years; male 40.9% (n = 18)] diagnosed with metastatic GEP-NENs were included in the analysis. All subjects were enrolled in the Department of Endocrinology and Neuroendocrine Tumours, Medical University of Silesia, Katowice. We analysed liver metastases. Patients with G3 grading or faintly vascularised lesions were excluded. HDF STIC volumes were acquired during USG examination. 4D indices [volumetric pulsatility index (vPI) and volumetric systolic/diastolic index (vS/D)] were calculated using dedicated software. There were no correlations between vS/D and Ki-67 [p = 0.67; r = -0.19; (-0.28-0.19)], CgA [p = 0.47; r = -0.11; (-0.38-0,19)], 5-HIAA [p = 0.52; r = -0.09 (-0.37-0.2)], serotonin [p = 0.83; r = -0.03 (-0.32-0.26)], and VCAM-1 (p = 0.62; r = 0.09 (-03-0.47)]. The were no correlations between vPI and Ki-67 [p = 0.29; r = -0.16 (-0.45-0.14)], CgA (p = 0.46; r = -0.11 (-0.39-0.19)], 5-HIAA [p = 0.52; r = -0.09 (-0.37-0.2)], serotonin [p = 0.82; r = -0.03 (-0.32-0.26)], and VCAM-1 (p = 0.62; r = -0.09 (-03-0.47)]. There was no significant difference between carcinoid versus non-carcinoid patients if compared by vS/D and vPI (p = 0.62, p = 0.61, respectively). HDF STIC seems not to be an efficient marker to assess advancement of NENs, due to lack of correlation with widely used and approved markers of progression.

Time-trend and recurrence analysis of pancreatic neuroendocrine tumors.

This study aimed to evaluate the evolving trends in clinicopathological features of pancreatic neuroendocrine tumors and to analyze the predictors of recurrence after curative resection. Data collected retrospectively from a single center between January 1990 and December 2017 were analyzed. Patients were categorized chronologically into three groups for evolving time-trend analysis. Overall, 542 patients (300 female, 55.4%) underwent surgical resection for pancreatic neuroendocrine tumors, including 435 (80.3%) with non-functional tumors. Time-trend analysis revealed that the surgically resected pancreatic neuroendocrine tumor number increased consistently; however, the incidental non-functional pancreatic neuroendocrine tumor number also increased over time (P < 0.001). The 5- and 10-year disease-free survival rates were 86.4 and 81.3%, respectively. The overall recurrence rate was 13.7%, and the most common site of recurrence was the liver. The median time to recurrence after primary surgery was 19.0 (range 0.8–236.3) months, and the median survival time after recurrence was 22.6 (range 0.4–126.9) months. On multivariate analysis, grade G3 pancreatic neuroendocrine tumors (hazard ratio 4.51; P < 0.001), lymph node metastasis (hazard ratio 2.46; P = 0.009), lymphovascular invasion (hazard ratio 3.62; P = 0.004), perineural invasion (hazard ratio 2.61; P = 0.004) and resection margin (hazard ratio 4.20; P = 0.003) were independent prognostic factors of disease-free survival. The surgically resected pancreatic neuroendocrine tumor number increased over time mainly because of an increase in incidentally discovered non-functional pancreatic neuroendocrine tumors. Grade G3 pancreatic neuroendocrine tumors, lymph node metastasis, lymphovascular invasion, perineural invasion and a positive resection margin were significant predictors of worse disease-free survival in patients with surgically resected pancreatic neuroendocrine tumors.