Rational treatment options for T1/2N0M0 squamous cell carcinoma of the anal canal: a population-based study combined with external validation.

BACKGROUND: Treatment options for T1/2N0M0 anal squamous cell carcinoma include chemotherapy, radiotherapy, chemoradiotherapy, and local excision, although the optimal treatment method has not been determined. METHODS: The National Cancer Institute Surveillance, Epidemiology and Results database was used to search and screen 1465 patients with cT1/2N0M0 anal squamous cell carcinoma who were clinically diagnosed between 2004 and 2016. Survival analysis was performed using the Kaplan-Meier method and log-rank test. Cox proportional hazards regression analysis was performed to screen independent prognostic factors and build a nomogram survival prediction model. According to the risk score, patients were divided into low, medium, and high risk groups using X-tile software. RESULTS: Age, sex, grade and cT stage were identified as independent prognostic factors for cT1/2N0M0 anal squamous cell carcinoma and were included in the nomogram to construct a prediction model. The C-index of the model was 0.770 [95% confidence interval (CI), 0.693-0.856], which was higher than the C-index of T stage 0.565 (95% CI, 0.550-0.612). Low-risk patients benefited from local resection, moderate-risk patients benefited from radiotherapy, and high-risk patients benefited from radiotherapy or chemoradiotherapy. This was confirmed using external validation data from the center. CONCLUSION: The nomogram developed in this study effectively and comprehensively evaluated the prognosis of patients with cT1/2N0M0 squamous cell carcinoma of the anal canal. Local excision is recommended for low risk patients, radiotherapy for moderate-risk patients, and radiotherapy or chemoradiotherapy for high-risk patients.

Sentinel lymph node biopsy in cT1-2N0 minor salivary gland cancer in oral cavity.

OBJECTIVE: To evaluate the efficacy of sentinel lymph node biopsy (SLNB) in cT1/2N0 minor salivary gland cancer (mSGC) located within the oral cavity. METHODS: A retrospective analysis was conducted on patients diagnosed with cT1/2N0 oral mSGC, who were categorized into two groups based on neck management approaches. The impact of SLNB versus observation on regional control and overall survival was assessed using a Cox model. RESULTS: A total of 177 patients were included in the study, with 53 cases undergoing SLNB. All patients had at least one sentinel lymph node, with the majority having two sentinel lymph nodes. The sentinel lymph nodes were predominantly situated in level I, followed by level II. Four patients had positive sentinel lymph nodes, all of whom had primary tumors in the tongue or the floor of the mouth, and were classified as cT2 stage. This yielded a sensitivity and specificity of 100%, a false negative rate of 0%, and a negative predictive value of 100% for SLNB in predicting occult metastasis. In terms of regional control, SLNB exhibited a reduced hazard ratio of 0.90 (95% confidence interval: 0.64-0.96) compared to observation. However, SLNB did not confer a superior overall survival benefit compared to observation. CONCLUSION: In patients with cT1/2N0 oral mSGC, SLNB proved to be both technically feasible and oncologically safe. When contrasted with observation, SLNB was associated with enhanced regional control, particularly recommending its use for cases of cT2 mSGC arising from the tongue or the floor of the mouth.

Quantitative MRI for Monitoring Metabolic Dysfunction-Associated Steatotic Liver Disease: A Test-Retest Repeatability Study.

BACKGROUND: Quantitative magnetic resonance imaging metrics iron-corrected T1 (cT1) and liver fat from proton density fat-fraction (PDFF) are both commonly used as noninvasive biomarkers for metabolic dysfunction-associated steatohepatitis (MASH); however, their repeatability in this population has rarely been characterized. PURPOSE: To quantify the variability of cT1 and liver fat fraction from PDFF in patients with biopsy-confirmed metabolic dysfunction-associated steatotic liver disease (MASLD) and MASH. STUDY TYPE: Prospective, single center. POPULATION: Twenty-one participants (female = 11, mean age 53 ± 24 years) with biopsy-confirmed MASLD, including 6 with MASH and fibrosis ≥2. FIELD STRENGTH/SEQUENCE: 3 T; T1 and T2* mapping for the generation of cT1 (shMOLLI: CardioMaps and 2D MDE, T1map-FIESTA and LMS MOST: StarMap, 2D Multi-Echo FSPGR) and magnitude-only PDFF sequence for liver fat quantification (LMS IDEAL: StarMap, 2D Multi-Echo FSPGR). ASSESSMENT: T1 mapping and PDFF scans were performed twice on the same day for all participants (N = 21), with an additional scan 2-4 weeks later for MASH patients with fibrosis ≥2 (N = 6). Whole liver segmentation masks were generated semi-automatically and average pixel counts within these masks were used for the calculation of cT1 and liver fat fraction. STATISTICAL TESTS: Bland-Altman analysis for repeatability coefficient (RC) and 95% limits of agreement (LOA) and intraclass correlation coefficient (ICC). RESULTS: Same-day RC was 32.1 msec (95% LOA: -36.6 to 24.2 msec) for cT1 and 0.6% (95% LOA: -0.5% to 0.7%) for liver fat fraction; the ICCs were 0.98 (0.96-0.99) and 1.0, respectively. Short-term RC was 65.2 msec (95% LOA: -63.8 to 76.5 msec) for cT1 and 2.6% (95% LOA: -2.8% to 3.1%) for liver fat fraction. DATA CONCLUSION: In participants with MASLD and MASH, cT1 and liver fat fraction measurements show excellent test-retest repeatability, supporting their use in monitoring MASLD and MASH. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 2.

EBUS-TBNA for mediastinal staging of centrally located T1N0M0 non-small cell lung cancer clinically staged with PET/CT.

BACKGROUND AND OBJECTIVE: To evaluate the diagnostic accuracy and clinical usefulness of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) for mediastinal staging of centrally located T1N0M0 non-small cell lung cancer (NSCLC) clinically staged with positron emission tomography/computed tomography (PET/CT). METHODS: We conducted a study that included patients with centrally located T1N0M0 NSCLC, clinically staged with PET/CT who underwent EBUS-TBNA for mediastinal staging. Patients with negative EBUS-TBNA underwent mediastinoscopy, video-assisted mediastinoscopic lymphadenectomy (VAMLA) and/or lung resection with systematic nodal dissection, that were considered the gold standard. The sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV), overall accuracy of EBUS-TBNA for diagnosing mediastinal metastases (N2 disease) and the number needed to treat (NNT: number of patients needed to undergo EBUS-TBNA to avoid a case of pathologic N2 disease after resection) were calculated. RESULTS: One-hundred eighteen patients were included. EBUS-TBNA proved N2 disease in four patients. In the remaining 114 patients who underwent mediastinoscopy, VAMLA and/or resection there were two cases of N2 (N2 prevalence 5.1%). The sensitivity, specificity, NPV, PPV and overall accuracy for diagnosing mediastinal metastases (N2 disease) were of 66%, 100%, 98%, 100% and 98%, respectively. The NNT was 31 (95% CI: 15-119). CONCLUSION: EBUS-TBNA in patients with central clinically staged T1N0M0 NSCLC presents a good diagnostic accuracy for mediastinal staging, even in a population with low prevalence of N2 disease. Therefore, its indication should be considered in the management of even these early lung cancers.

Survival benefits of postoperative radiotherapy in patients with cT1 - 2N1M0 breast cancer after neoadjuvant chemotherapy: a SEER-based population study.

BACKGROUND: Whether patients with cT1 - 2N1M0 breast cancer can benefit from postoperative radiotherapy (RT) after receiving neoadjuvant chemotherapy (NAC) has been controversial. Therefore, the purpose of this study was to explore whether postoperative RT can benefit this group of patients in terms of survival. METHODS: We used Surveillance, Epidemiology, and End Results (SEER) data to conduct a retrospective review of women with cT1 - 2N1M0 breast cancer diagnosed between 20 and 80 years of age who received NAC between 2010 and 2015. Our study compared the impact of postoperative RT on overall survival (OS) and cancer-specific survival (CSS) in breast cancer patients using propensity score matching (PSM) and performed subgroup analysis. RESULTS: This study finally included 1092 cT1 - 2N1M0 breast cancer patients. Regardless of the patient's PSM status, postoperative RT was significantly associated with OS of cT1-2N1M0 breast cancer patients who received NAC. Specifically, the 10-year OS rate was 78.7% before PSM matching, compared with 71.1% in patients who did not receive postoperative RT, and the difference was more significant after PSM matching, which was 83.1% and 71.1% respectively. However, postoperative RT did not significantly benefit CSS in patients with cT1 - 2N1M0 breast cancer who received NAC. The 10-year CSS rate was 81.4% VS 76.2% (P = 0.085) before PSM matching and 85.8% VS 76.2%(P = 0.076) after matching. Due to the intersection of OS and CSS curves, this restricted mean survival time (RMST) method was chosen as a supplement. After 60 months, the OS difference in RMST between the postoperative RT group and the non-radiotherapy (noRT) group was 7.37 months (95%CI: 0.54-14.21; P = 0.034), and the CSS difference was 5.18 months (95%CI: -1.31-11.68; P = 0.118). Subgroup analysis found that in patients with right-sided breast cancer, postoperative RT improved the patient's OS (HR = 0.45, 95%CI: 0.21-0.95, P = 0.037) and CSS (HR = 0.42, 95%CI: 0.18-0.98, P = 0.045). CONCLUSIONS: Our results showed that additional postoperative RT improved the OS of cT1 - 2N1M0 breast cancer patients who received NAC, but failed to improve their CSS. It is worth noting that in the subgroup analysis of patients with right-sided breast cancer, we observed significant improvements in OS and CSS. And further prospective studies are still needed to verify the effect of postoperative RT in different subgroups.

Evaluation of selected circulating cytokines from the IL-6 family - interleukin 6, oncostatin M, and cardiotrophin-1 - in gastro-entero-pancreatic and bronchial neuroendocrine tumours.

Introduction: The incidence of neuroendocrine tumours (NETs) increased over the last years. Most of them are non-functioning, and the course of the disease is asymptomatic for a long time. This results in late diagnosis at an advanced stage. The aim of our study was the evaluation of selected circulating cytokines of interleukin-6 family - interleukin 6 (IL-6), oncostatin M (OSM), and cardiotrophin-1 (CT1) - in NETs. Material and methods: The study group comprised 80 patients (56%) in several subgroups, including gastroenteropancreatic (GEPNETs, n = 64, 80%) and bronchopulmonary neuroendocrine tumours (BPNETs, n = 16; 20%). Serum IL-6, OSM, and CT1 concentrations were tested using ELISA. Results: The median concentration of IL-6 was 41.5 pg/ml in the study group and 32.6 pg/ml in the control group, and the difference was statistically significant (p < 0.001). The concentration of OSM was significantly lower in the study group than in the control group (p < 0.001), at 105.6 pg/ml and 115.5 pg/ml, respectively. There was a significant difference (p < 0.01) in concentration of CT1 in the study group (222.0 pg/ml) and controls (267.2 pg/ml). Our investigation into selected IL-6 family cytokines revealed differential modulation of signal transduction pathways. Conclusions: These findings suggest that despite utilising a common signalling transducer, individual IL-6 family cytokines exert distinct biological effects on neuroendocrine tumour development. Notably, IL-6 appears to promote tumourigenesis, while OSM and CT1 exhibit inhibitory effects on gastro-entero-pancreatic and bronchial neuroendocrine tumour development. Further studies are necessary to validate the diagnostic utility of IL-6 family cytokines in NETs.

Taurine and Creatine Transporters as Potential Drug Targets in Cancer Therapy.

Cancer cells are characterized by uncontrolled growth, proliferation, and impaired apoptosis. Tumour progression could be related to poor prognosis and due to this fact, researchers have been working on novel therapeutic strategies and antineoplastic agents. It is known that altered expression and function of solute carrier proteins from the SLC6 family could be associated with severe diseases, including cancers. These proteins were noticed to play important physiological roles through transferring nutrient amino acids, osmolytes, neurotransmitters, and ions, and many of them are necessary for survival of the cells. Herein, we present the potential role of taurine (SLC6A6) and creatine (SLC6A8) transporters in cancer development as well as therapeutic potential of their inhibitors. Experimental data indicate that overexpression of analyzed proteins could be connected with colon or breast cancers, which are the most common types of cancers. The pool of known inhibitors of these transporters is limited; however, one ligand of SLC6A8 protein is currently tested in the first phase of clinical trials. Therefore, we also highlight structural aspects useful for ligand development. In this review, we discuss SLC6A6 and SLC6A8 transporters as potential biological targets for anticancer agents.

Clinical Utility of Magnetic Resonance Imaging Biomarkers for Identifying Nonalcoholic Steatohepatitis Patients at High Risk of Progression: A Multicenter Pooled Data and Meta-Analysis.

BACKGROUND & AIMS: Nonalcoholic fatty liver disease (NAFLD) is increasing in prevalence worldwide. NAFLD is associated with excess risk of all-cause mortality, and its progression to nonalcoholic steatohepatitis (NASH) and fibrosis accounts for a growing proportion of cirrhosis and hepatocellular cancer and thus is a leading cause of liver transplant worldwide. Noninvasive precise methods to identify patients with NASH and NASH with significant disease activity and fibrosis are crucial when the disease is still modifiable. The aim of this study was to examine the clinical utility of corrected T1 (cT1) vs magnetic resonance imaging (MRI) liver fat for identification of NASH participants with nonalcoholic fatty liver disease activity score ≥4 and fibrosis stage (F) ≥2 (high-risk NASH). METHODS: Data from five clinical studies (n = 543) with participants suspected of NAFLD were pooled or used for individual participant data meta-analysis. The diagnostic accuracy of the MRI biomarkers to stratify NASH patients was determined using the area under the receiver operating characteristic curve (AUROC). RESULTS: A stepwise increase in cT1 and MRI liver fat with increased NAFLD severity was shown, and cT1 was significantly higher in participants with high-risk NASH. The diagnostic accuracy (AUROC) of cT1 to identify patients with NASH was 0.78 (95% CI, 0.74-0.82), for liver fat was 0.78 (95% CI, 0.73-0.82), and when combined with MRI liver fat was 0.82 (95% CI, 0.78-0.85). The diagnostic accuracy of cT1 to identify patients with high-risk NASH was good (AUROC = 0.78; 95% CI, 0.74-0.82), was superior to MRI liver fat (AUROC = 0.69; 95% CI, 0.64-0.74), and was not substantially improved by combining it with MRI liver fat (AUROC = 0.79; 95% CI, 0.75-0.83). The meta-analysis showed similar performance to the pooled analysis for these biomarkers. CONCLUSIONS: This study shows that quantitative MRI-derived biomarkers cT1 and liver fat are suitable for identifying patients with NASH, and cT1 is a better noninvasive technology than liver fat to identify NASH patients at greatest risk of disease progression. Therefore, MRI cT1 and liver fat have important clinical utility to help guide the appropriate use of interventions in NAFLD and NASH clinical care pathways.

Pleiotropic, Unique and Shared Responses Elicited by IL-6 Family Cytokines in Human Vascular Endothelial Cells.

Vascular endothelial cells express glycoprotein 130 (gp130), which is utilized as a signaling receptor by cytokines in the interleukin-6 (IL-6) family. Several IL-6 family cytokines can be found in the circulatory system during physiological or pathological conditions, and may influence endothelial function and response. This study evaluated and compared the cellular and molecular responses induced by IL-6 family cytokines in human endothelial cells. A proteomic analysis showed that IL-6 family cytokines induce the release of a range of proteins from endothelial cells, such as C-C motif chemokine ligand 23, hepatocyte growth factor, and IL-6. Pathway analysis indicated that gp130-signaling in endothelial cells regulates several functions related to angiogenesis and immune cell recruitment. The present investigation also disclosed differences and similarities between different IL-6 family cytokines in their ability to induce protein release and regulate gene expression and intracellular signaling, in regards to which oncostatin M showed the most pronounced effect. Further, this study showed that soluble gp130 preferentially blocks trans-signaling-induced responses, but does not affect responses induced by classic signaling. In conclusion, IL-6 family cytokines induce both specific and overlapping molecular responses in endothelial cells, and regulate genes and proteins involved in angiogenesis and immune cell recruitment.

Increased Expression of Cardiotrophin-1 in Cardiomyopathy Patients.

Cardiomyopathy (CM) is a condition of cardiac dysfunction. It is one of the leading causes of mortality in which both genetic and environmental factors are involved. Cardiotrophin-1 (CT-1) level in plasma is associated with CM. It affects the cardiomyocyte differentiation. To evaluate the expression of CT-1 in cardiomyopathy, this study was done on CM subjects attending the Fatima Memorial Hospital, Lahore, Pakistan, between January and June, 2016. A total of 40 subjects were enrolled who were divided into two groups; CM group (n = 20) and a control group (n = 20). A self-designed questionnaire was filled in by each subject to collect data regarding age, body mass index (BMI) and CM history. RNA was isolated from blood after its quantification, cDNA was prepared and reverse-transcriptase-polymerase chain reaction (RT-PCR) was performed for expression of CT-1. The mean age in CM subjects was 40.1±6.03 years, while it was 35.0±3.7 years in the control group. The mean expression of CT-1 in the CM subjects was 5.2±0.66, while it was 1.00±0.001 in the control group. A highly significant difference was observed in CT-1 expression in the CM group, and expression was significantly correlated with age and BMI in CM subjects.

Genome-wide and Mendelian randomisation studies of liver MRI yield insights into the pathogenesis of steatohepatitis.

BACKGROUND & AIMS: MRI-based corrected T1 (cT1) is a non-invasive method to grade the severity of steatohepatitis and liver fibrosis. We aimed to identify genetic variants influencing liver cT1 and use genetics to understand mechanisms underlying liver fibroinflammatory disease and its link with other metabolic traits and diseases. METHODS: First, we performed a genome-wide association study (GWAS) in 14,440 Europeans, with liver cT1 measures, from the UK Biobank. Second, we explored the effects of the cT1 variants on liver blood tests, and a range of metabolic traits and diseases. Third, we used Mendelian randomisation to test the causal effects of 24 predominantly metabolic traits on liver cT1 measures. RESULTS: We identified 6 independent genetic variants associated with liver cT1 that reached the GWAS significance threshold (p <5×10-8). Four of the variants (rs759359281 in SLC30A10, rs13107325 in SLC39A8, rs58542926 in TM6SF2, rs738409 in PNPLA3) were also associated with elevated aminotransferases and had variable effects on liver fat and other metabolic traits. Insulin resistance, type 2 diabetes, non-alcoholic fatty liver and body mass index were causally associated with elevated cT1, whilst favourable adiposity (instrumented by variants associated with higher adiposity but lower risk of cardiometabolic disease and lower liver fat) was found to be protective. CONCLUSION: The association between 2 metal ion transporters and cT1 indicates an important new mechanism in steatohepatitis. Future studies are needed to determine whether interventions targeting the identified transporters might prevent liver disease in at-risk individuals. LAY SUMMARY: We estimated levels of liver inflammation and scarring based on magnetic resonance imaging of 14,440 UK Biobank participants. We performed a genetic study and identified variations in 6 genes associated with levels of liver inflammation and scarring. Participants with variations in 4 of these genes also had higher levels of markers of liver cell injury in blood samples, further validating their role in liver health. Two identified genes are involved in the transport of metal ions in our body. Further investigation of these variations may lead to better detection, assessment, and/or treatment of liver inflammation and scarring.

Comparison of perioperative outcomes of robot-assisted partial nephrectomy without renorrhaphy: Comparative outcomes of cT1a versus cT1b renal tumors.

OBJECTIVES: To assess the perioperative outcomes of robot-assisted partial nephrectomy without renorrhaphy for cT1b renal tumors compared with cT1a. METHODS: From February 2015 to May 2018, 100 robot-assisted partial nephrectomy patients who underwent robot-assisted partial nephrectomy without renorrhaphy for renal tumors were included. We retrospectively reviewed the medical records, and compared the perioperative outcomes of 66 and 34 patients for cT1a and cT1b tumors, respectively. Inner suture was carried out in the opened collecting system or renal sinus, whereas parenchymal renorrhaphy was not. For hemostasis, the soft-coagulation system was used, and absorbable hemostats were placed on the resection bed. RESULTS: The median tumor size and RENAL nephrometry score were significantly different between the two groups (cT1a vs cT1b: 23.5 vs 45 mm, P < 0.001, 6 vs 8, P < 0.001). The median operating time and warm ischemic time were significantly longer in the cT1b group than in the cT1a group (154 vs 184 min, P < 0.001; 14 vs 21 min, P < 0.001). The median blood loss was not significantly different (2.5 vs 50 mL, P = 0.109). The positive surgical margin rate was 4.5% versus 11.7% (P = 0.22). Postoperative complications classified as Clavien-Dindo grade III or higher were port-site herniation (one patient), acute cholecystitis (one patient) and pseudoaneurysm (one patient) in the cT1b group. Urinary leakage was not observed in the two groups. CONCLUSIONS: Robot-assisted partial nephrectomy without renorrhaphy using the soft-coagulation system and absorbable hemostats appears to be feasible for renal or cT1b tumors. However, longer warm ischemic time and a high rate of complications can be expected compared with cT1a tumors.

Potential clinical treatment of colitis with cardiotrophin-1.

In a recent issue of Clinical Science, Prieto-Vicente et al. [Clin. Sci. (2018) 132, 985-1001] have smartly demonstrated a potential new use of cardiotrophin-1 (CT-1) to treat and palliate an inflammatory bowel disease such as ulcerative colitis. In that work, authors report that in ulcerative colitic mice, administration of exogenous recombinant CT-1 (rCT-1) promotes lower colon damage and lower disease activity index, reducing systemic levels of tumor necrosis factor α (TNF-α) and also diminishing TNF-α expression in colon together with the reduction in other common inflammation markers. Besides, in vivo rCT-1 administration induces activation of several molecular pathways, including nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) and signal transducer and activator of transcription (STAT)-3, and abolishes bacterial translocation from intestine to other organs, including mesenteric ganglia, lungs, and spleen. Additionally, these results were nicely corroborated in CT-1 depleted mice; in which colon damage and ulcerative colitis severity were greater compared with the wild-type counterparts. All together, these results suggested that CT-1 could be a promising new therapeutic approach for treating inflammatory bowel disease, particularly ulcerative colitis. However, further studies are required to determine its major mechanisms of action and the potential efficacy of CT-1 in human inflammatory bowel diseases.

Serum and gene expression levels of CT-1, IL-6, and TNF-α after a lifestyle intervention in obese children.

BACKGROUND: Inflammation related molecules such as tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), and cardiotrophin-1 (CT-1) are highly expressed in obese individuals and could partly explain some comorbidities associated to obesity. In obese children, lifestyle interventions are able to lower inflammation and reduce cardiovascular risk factors associated with obesity. The aim of the present work was to study changes in inflammation-related molecules serum and peripheral blood mononuclear cells (PBMC) transcript levels after a 10-week lifestyle intervention in obese children and asses their potential association with glucose metabolism. METHODS: Twenty-three obese children (mean age 11.5 years; 48% males) underwent a 10-week lifestyle not controlled intervention trial. Anthropometric and biochemical measurements were analyzed. Transcript analysis for CT-1, IL-6, and TNF-α in PBMC were performed by RT-PCR. Serum cytokine levels were also measured at baseline and after 10-weeks. RESULTS: Participants achieved a significant reduction in body adiposity (0.34 decrease in body mass index-standard deviation), total cholesterol, and glucose levels after 10-weeks. A Significant decrease in serum TNF-α and C reactive protein (CRP) were observed. CT-1 transcript levels were significantly reduced (P = .005) after lifestyle intervention, and these changes were significantly correlated with changes in serum CT-1 levels (r = 0.451; P = .031). In multiple regression analysis baseline CT-1 transcript levels were positively associated with final insulin (R2 = 0.506; P = .035) and HOMA-IR values (R2 = 0.473; P = .034). CONCLUSIONS: We reported that serum CRP, TNF-α, as well as PBMC CT-1 transcript levels were reduced after lifestyle intervention in obese children. More studies are needed to clarify the role of inflammation-related molecules in glucose metabolism.

Introduction of Microwave Ablation Into a Renal Ablation Practice: Valuable Lessons Learned.

OBJECTIVE: The purpose of this study was to evaluate the early outcomes of percutaneous microwave ablation (MWA) for clinical stage T1 (cT1) renal masses when performed within a high-volume ablation practice with critical emphasis on procedural safety. MATERIALS AND METHODS: A retrospective review of a percutaneous renal ablation registry identified 26 patients with a total of 27 cT1 renal masses treated with MWA between 2011 and 2017. Mean patient age was 63.8 years and 16 (61.5%) patients were male. Mean renal mass size ± SD was 2.3 ± 0.8 cm (range, 1.1-4.7 cm). The main outcome parameters investigated were technical success, local tumor progression, survival rates, and complications. Complications were categorized using the Clavien-Dindo classification system. Rates of local progression-free and cancer-specific survival (PFS and CSS, respectively) were estimated using the Kaplan-Meier method. RESULTS: Technical success was 100% on contrast-enhanced CT or MRI performed immediately after renal MWA. Twenty-four patients (92%) with 25 tumors had follow-up imaging for 3 months or longer (mean, 20.6 ± 11.6 months), with no local tumor recurrences identified. Estimated 3-year local PFS and CSS were 96% and 94%, respectively. The overall complication rate was 19.2%; two patients (7.7%) experienced minor complications (grade I or II) and three patients (11.5%) experienced major bleeding or urinary-related complications (grade III or higher), including one death. CONCLUSION: This study suggests that percutaneous MWA is a promising minimally invasive treatment option for cT1 renal masses. Nonetheless, major bleeding and urinary-related complications can occur, and further studies are needed to determine optimal patient and tumor selection for renal MWA.

The value of diagnostic endoscopic submucosal dissection for patients with clinical submucosal invasive early gastric cancer.

BACKGROUND: The standard treatment for clinical submucosal invasive (cT1b) early gastric cancer is gastrectomy. However, Japanese gastric cancer treatment guidelines list endoscopic submucosal dissection (ESD) as an option for treating limited early gastric cancer cases. ESD can be curative depending on the pathological characteristics of resected specimens. Thus, we aimed to clarify the benefits and disadvantages of preceding ESD for early gastric cancer. METHODS: We retrospectively analyzed patients who underwent ESD or curative gastrectomy for cT1b gastric cancer with differentiated adenocarcinoma 30 mm or less in diameter. Patients who underwent ESD irrespective of undergoing gastrectomy were assigned to the ESD group (n = 107), and those who underwent gastrectomy without undergoing ESD were assigned to the non-ESD group (n = 181). Clinicopathological characteristics were assessed, and the short-term and long-term outcomes of patients were compared. RESULTS: The criteria for curative resection were satisfied by 83 patients (28.8%), and preceding ESD did not affect the surgical outcomes of gastrectomy. Two patients (1.9%) who underwent ESD had an unscheduled total gastrectomy. The en bloc and complete resection rates of ESD were 99.0% and 84.1% respectively. Nine patients (8.4%) experienced intraprocedure perforation and postprocedure bleeding caused by ESD. Overall survival (hazard ratio 1.38; P = 0.302) and cause-specific survival (hazard ratio 0.96; P = 0.944) were comparable between groups. CONCLUSIONS: The stomach was preserved in 28.8% of patients, and preceding ESD did not show obvious disadvantages. Therefore, diagnostic ESD should be considered as an initial treatment for limited cT1b gastric cancer cases.

Two-stage CO2-laser-assisted bilateral cordectomy for cT1b glottic carcinoma.

PURPOSE: The aim of the present paper was to investigate the oncological safety of two-stage bilateral cordectomy for the treatment of cT1b glottic SCC, and to compare its oncological outcome and synechia development rate with those of single-stage procedures. MATERIALS AND METHODS: A retrospective cohort study was performed at the Otolaryngology Unit of Vittorio Veneto Laryngeal Cancer Center (Italy). The prognostic significance of clinical, pathological and surgical factors was also investigated, in terms of recurrence rate and disease-free survival, in a univariate statistical setting. RESULTS: Our results indicate that patients treated with primary two-stage bilateral cordectomy achieved local control in 96% of cases, with 95% disease-specific and 88% overall survival rates, and a 95% organ preservation rate, with anterior synechiae developing in 1 case. Involvement of the deep surgical margins correlated with a worse prognosis. Patients developed anterior synechiae less frequently after two-stage bilateral cordectomy, and experienced no higher recurrence rate or shorter disease-free survival than patients treated with a single-stage procedure. CONCLUSIONS: Two-stage bilateral cordectomy is a safe and effective procedure. In selected patients it could be considered the primary approach for the treatment of early glottic cT1b carcinomas.

Long-term prognostic outcome of cT1 gastric cancer patients who underwent laparoscopic gastrectomy after 5-year follow-up.

PURPOSE: We have reported that short-term and middle-term clinical outcomes including prognosis after laparoscopy-assisted gastrectomy (LAG) are excellent in cT1 gastric cancer. METHODS: In this study, long-term prognosis was finally confirmed in detail in 491 cT1 gastric cancer patients who underwent LAG between 1998 and 2010, where clinical course was completely pursued for recurrent cases. RESULTS: Among the 491 cases, follow-up examination at 5 years (60 months) after operation was done in 423 (86.2 %). Recurrent cases were seen in nine cases (1.8 %) who inevitably died despite aggressive multimodality treatments. The initial recurrent sites were the peritoneum in three, the liver in two, the bone in one, the ovary in one, the liver/bone in one, and the Virchow lymph node/bone in one. As a result, the 5-year disease-specific survival (DSS) was 98.3 %. cT1 gastric cancer was finally diagnosed as pathological stages IA to III, and the 5-year DSS was 99.7 % in pathological stage IA, 96.9 % in pathological stage IB, and 81 % in pathological stage II/III. The initial recurrent sites were the liver/bone in stage IA (M/N0), the liver in stage IB (MP/N0), the liver in stage IIA (MP/N1), the liver and the ovary in two stages IIB (T1N3), 3 peritoneum and 1 Virchow lymph node/bone in four stage III cases. Importantly, there were no initial recurrences in the regional lymph node, and all recurrences were seen within 5 years after operation. CONCLUSIONS: Although long-term prognostic outcome was extremely good in cT1 gastric cancer patients who underwent LAG, cases with recurrence inevitably died due to disease progression.

Vascular Structure Identification in Intraoperative 3D Contrast-Enhanced Ultrasound Data.

In this paper, a method of vascular structure identification in intraoperative 3D Contrast-Enhanced Ultrasound (CEUS) data is presented. Ultrasound imaging is commonly used in brain tumor surgery to investigate in real time the current status of cerebral structures. The use of an ultrasound contrast agent enables to highlight tumor tissue, but also surrounding blood vessels. However, these structures can be used as landmarks to estimate and correct the brain shift. This work proposes an alternative method for extracting small vascular segments close to the tumor as landmark. The patient image dataset involved in brain tumor operations includes preoperative contrast T1MR (cT1MR) data and 3D intraoperative contrast enhanced ultrasound data acquired before (3D-iCEUS(start) and after (3D-iCEUS(end) tumor resection. Based on rigid registration techniques, a preselected vascular segment in cT1MR is searched in 3D-iCEUS(start) and 3D-iCEUS(end) data. The method was validated by using three similarity measures (Normalized Gradient Field, Normalized Mutual Information and Normalized Cross Correlation). Tests were performed on data obtained from ten patients overcoming a brain tumor operation and it succeeded in nine cases. Despite the small size of the vascular structures, the artifacts in the ultrasound images and the brain tissue deformations, blood vessels were successfully identified.

Hypertension in adult Fabry's disease: is cardiotrophin-1 a diagnostic biomarker?

BACKGROUND: Cardiotrophin-1 (CT-1), a cytokine produced by cardiomyocytes and non-cardiomyocytes in conditions of stress, can be used as a biomarker of left ventricular hypertrophy and dysfunction in hypertensive patients. Hypertension is one of the main adverse events in the third and last phase of Fabry's disease (FD). We measured CT-1 in order to examine its correlation with the vascular and cardiac alterations at different ages and assess its potential for use as a biomarker of hypertension in FD. FINDINGS: The level of CT-1 was clearly higher in hypertensive adults than in adult FD patients. FD patients show a small, non-significant decrease in plasma CT-1 with age, while in hypertensive patients CT-1 in plasma rises strongly and highly significantly with age. CONCLUSIONS: CT-1 can be considered a good biomarker of the progression of hypertension with age, but particular care is needed when following hypertension in FD patients, since CT-1 does not correlate the same way with this disease.