Convolutional Neural Networks for Optical Discrimination Between Histological Types of Colorectal Polyps Based on White Light Endoscopic Images.

The objective of this study was to compare different convolutional neural networks (CNNs), as employed in a Python-produced deep learning process, used on white light images of colorectal polyps acquired during the process of a colonoscopy, in order to estimate the accuracy of the optical recognition of particular histologic types of polyps. The TensorFlow framework was used for Inception V3, ResNet50, DenseNet121, and NasNetLarge, which were trained with 924 images, drawn from 86 patients.

Outcomes in patients receiving palliative chemotherapy for advanced biliary tract cancer.

BACKGROUND & AIMS: Advanced biliary tract cancer (ABTC) is associated with a poor prognosis. Real-world data on the outcome of patients with ABTC undergoing sequential chemotherapies remain scarce, and little is known about treatment options beyond the established first- and second-line treatments with gemcitabine + cisplatin and FOLFOX. This study aimed to evaluate the outcome of patients with regard to different oncological therapies and to identify prognostic factors. METHODS: From January 2010 until December 2019, 142 patients started palliative chemotherapy at our tertiary care liver center. Overall survival (OS) was calculated using Kaplan-Meier plots. Prognostic factors were evaluated using cox proportional-hazards. RESULTS: Patients received a median number of 2 lines of chemotherapy. Median OS was 6.7, 15.2 and 18.2 months for patients who received 1, 2 and 3 lines of chemotherapy, respectively. Patients treated with FOLFIRINOX had a significantly extended OS of 23.8 months (log-rank test: p = 0.018). The univariate cox regression analysis identified several clinical parameters associated with survival (e.g. albumin, bilirubin, carcinoembryonic antigen, carbohydrate antigen 19-9 levels). CONCLUSIONS: Our study provides real-world data on the prognosis of ABTC including survival times for patients receiving third and later lines of chemotherapy. LAY SUMMARY: Real-world data depicting the outcome of patients with advanced biliary tract cancer outside the framework of controlled trials remain rare despite being extremely important for clinical decision-making. This study therefore provides important real-world data on the established first- and second-line treatments with gemcitabine + cisplatin and FOLFOX, as well as on other chemotherapy regimens or later lines of chemotherapy. It further demonstrates that the use of FOLFIRINOX is associated with promising survival and that there is an association between various clinical parameters such as pre-therapeutic albumin, bilirubin or carbohydrate antigen 19-9 levels and survival.

Predictive Value of Preoperative Endoscopic Ultrasound (EUS) After Neoadjuvant Chemotherapy in Locally Advanced Esophagogastric Cancer - Data From a Randomized German Phase II Trial.

PURPOSE: The role of EUS before or after neoadjuvant chemotherapy (nCTX) in advanced esophagogastric cancer (EGC) is still unclear. The phase II NEOPECX trial evaluated perioperative chemotherapy with or without panitumumab in this setting. The aim of this sub-study was to investigate the prognostic value of EUS-guided preoperative staging before and after nCTX. MATERIALS AND METHODS: Preoperative yuT/yuN stages by EUS were compared with histopathological ypT/ypN stages after curative resection. Reduction in T-stage from baseline to preoperative EUS was defined as downstaging (DS+) and compared to progression-free (PFS) and overall survival (OS) of patients without downstaging (DS-). In addition, preoperative EUS N-stages (positive N+ or negative N-) were correlated with clinical data. RESULTS: The preoperative yuT-stage correlated with the ypT-stage in 48% of cases (sensitivity 48%, specificity 52%), while the preoperative yuN-stage correlated with the ypN-stage in 64% (sensitivity 76%, specificity 52%). Within DS+ patients who were downstaged by ≥ 2 T-categories, a trend towards improved OS was detected (median OS DS+: not reached (NR), median OS DS-: 38.5 months (M), p=0.21). Patients with yuN+ at preoperative EUS had a worse outcome than yuN- patients (median OS yuN-: NR, median OS yuN+: 38.5 M, p = 0.013). CONCLUSION: The diagnostic accuracy of EUS to predict the response after nCTX in patients with advanced EGC is limited. In the current study the endosonographic detection of lymph node metastasis after nCTX indicates a poor prognosis. In the future, preoperative EUS with sectional imaging procedures may be used to tailor treatment for patients with advanced EGC.

The Addition of Transarterial Chemoembolization to Palliative Chemotherapy Extends Survival in Intrahepatic Cholangiocarcinoma.

Incidence and mortality of intrahepatic cholangiocarcinoma (iCCA) have been increasing continuously. Recent studies suggest that the combination of palliative chemotherapy (pCTX) and transarterial chemoembolization (TACE) improves overall survival (OS). This study aimed to evaluate the outcome of patients treated with TACE and pCTX in unresectable iCCA at our tertiary care center. A group of 14 patients was treated with both pCTX and TACE. The non-randomized control group of 59 patients received pCTX alone. Patients received a median of two pCTX lines in both groups. Those treated with TACE underwent a median number of 3.5 sessions. Median OS from the time of unresectability was 26.2 months in the pCTX + TACE group versus 13.1 months in the pCTX group (p = 0.008). Controlling for albumin, bilirubin, ECOG (Eastern Cooperative Oncology Group) performance status, and UICC (Union for International Cancer Control) stage, the addition of TACE still conferred an OS benefit of 12.95 months (p = 0.014). A propensity score matching analysis yielded an OS benefit of 14 months from the time of unresectability for the pCTX + TACE group (p = 0.020). The addition of TACE to pCTX may provide an OS benefit for patients with unresectable iCCA. Thus, patients with liver-dominant iCCA undergoing standard-of-care pCTX should be considered for additional treatment with TACE.

Advances in the endoscopic management of malignant biliary obstruction.

Biliary obstruction is common in pancreatobiliary malignancies and has a negative impact on the patient's quality of life, postoperative complications, and survival rates. Particularly in the last decade, there has been enormous progress regarding the diagnostic and therapeutic options in patients with malignant biliary obstruction. Endoscopy has given a new insight in this direction and novel techniques have been developed for the better characterization and treatment of malignant strictures. We herein summarize the available data on the different endoscopic techniques, and clarify their role in the diagnosis and treatment of malignant biliary obstructive disease. Finally, we propose an algorithm that can facilitate management decisions in these patients.

Terminal Ileitis due to Yersinia Infection: An Underdiagnosed Situation.

Endoscopy is currently the gold standard for the diagnosis of inflammatory bowel disease (IBD). The presence of macroscopic lesions along with the microscopic detection of inflammatory infiltration in the terminal ileum often leads the gastroenterologist to the diagnosis of Crohn's disease (CD). However, some of these cases could be, in fact, an infection caused by Yersinia spp., accompanied or not with CD, which could be easily diagnosed with the identification of serum antibodies against Yersinia outer protein antigens (YOP antigens). Since Yersiniosis is considered to be an uncommon situation, food and water are not usually checked for the possibility of contamination by Yersinia. Therefore, it is reasonable to assume that the true prevalence of Yersinia infection in patients with terminal ileitis is probably underestimated. In this article, we review the most important data regarding the various aspects of Yersinia infection with special focus on its pathophysiology and diagnosis. We recommend testing for serum antibodies against YOP antigens in all patients with an endoscopic and histological image of terminal ileitis in order to identify Yersiniosis in conjunction or not with terminal ileum CD.

Safety and efficacy of afatinib as add-on to standard therapy of gemcitabine/cisplatin in chemotherapy-naive patients with advanced biliary tract cancer: an open-label, phase I trial with an extensive biomarker program.

BACKGROUND: To date, the cornerstone of treatment in patients with advanced or metastatic cholangiocarcinoma (CCA) is systemic chemotherapy based on a combination of gemcitabine and a platinum derivative. Other therapeutic approaches including targeted agents and tyrosine kinase inhibitors (TKI) have demonstrated disappointing results, highlighting the complexity of CCA. Recently, drugs aiming at the inhibition of HER-receptors have shown first therapeutic benefit in patients with late stage disease. The aim of this phase I study was to test the dose level toxicities (DLTs), safety and efficacy of afatinib, a highly specific panErbB family receptor TKI, in chemotherapy naive patients with advanced CCA in conjunction with an extensive biomarker program. METHODS: Afatinib was administered continuously p. o. as add-on in patients with advanced CCA who received conventional chemotherapy with gemcitabine/cisplatin. A classical 3 + 3 phase I study was employed, while the maximum tolerated dose (MTD) of oral afatinib was determined in a 2 step dose escalation. Safety, overall survival (OS) and progression free survival (PFS) were evaluated for all patients. Finally, a translational biomarker analysis was conducted for the EGFR and VEGF signalling cascades. RESULTS: Overall, 9 patients were enrolled. Further recruitment was discontinued due to lack of efficacy results of the tested drug in other indications. 30 mg afatinib could be safely administered as add-on to 80% of standard dose gemcitabine/cisplatin. The mOS and mPFS were 7.7 and 6.0 months, respectively. Diarrhoea and haematological disorders were the most common observed AEs. Almost all patients overexpressed EGFR on their tumour tissues, whereas none of them expressed mutations in Exons 18, 19 and 21. Non-responders showed a higher variation of VEGF-C, -D, leptin and sEGFR in their sera. CONCLUSIONS: Afatinib failed to show survival benefits in combination with gemcitabine/cisplatin in patients with advanced CCA. Mutational analysis of EGFR and pathways associated with VEGF-C, -D and leptin might show promising results in future studies. CLINICAL TRIALS REGISTRATION: NCT01679405 August, 2012.

Feasibility Trial of the Newly Introduced Optical Enhancement Technology in Patients with Gastroesophageal Reflux Disease.

BACKGROUND: Optical Enhancement technology (OE) combines bandwidth-limited light and image enhancement processing technology to enhance subtle mucosal and vascular details. This is the first study assessing the new technology for the diagnosis of gastroesophageal reflux disease (GERD). PATIENTS AND METHODS: Consecutive patients with GERD and controls were prospectively included. The distal esophagus was examined in all quadrants with high definition white-light endoscopy (HD-WLE) followed by OE and biopsies for histopathological analysis. Features observed only by OE were compared between controls and patients with GERD. RESULTS: A total of 100 areas were evaluated. About 56% of patients had a diagnosis of GERD. The mean age of patients was 53 years (range 27-89 years), 60% were female. Compared to controls, patients with diagnosis of GERD showed significantly more often tortuosity (p = 0.042), dilation (p = 0.0003), and increased number (p = 0.001) of intrapapillary capillary loops (IPCLs). In addition, increased vascularity and mucosal breaks were significantly more often found in patients with GERD as compared to controls (p < 0.05). On multivariate analysis, increased number and dilation of IPCL were the best predictors of GERD. CONCLUSIONS: The newly introduced OE technology significantly improves the diagnosis of GERD compared to HD-WLE. The results should be confirmed in a multicenter trial.

Lapatinib with ECF/X in the first-line treatment of metastatic gastric cancer according to HER2neu and EGFR status: a randomized placebo-controlled phase II study (EORTC 40071).

PURPOSE: HER2-targeted therapy with trastuzumab and (CF/X) prolonged overall survival (OS) in metastatic HER2neu+ gastric carcinoma (GC). Lapatinib inhibits both EGFR and HER2neu. We investigated the efficacy and safety of lapatinib with epirubicin (E) + CF/X in GC according to HER2neu and EGFR status. METHODS: Tumors from chemotherapy-naïve patients were screened centrally by fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC). Patients with EGFR and/or HER2neu expression or amplification were allocated to three strata based on EGFR/HER2neu status and were randomized to lapatinib (arm A) or placebo (arm B), with 6 cycles of ECF or ECX (investigator-selected). The primary endpoint was progression-free survival (PFS) in stratum 3. RESULTS: 29 of 72 screened patients were randomized to strata 1 (HER2neu+: by FISH and IHC, n = 6), 2 (HER2neu-: by FISH/+ by IHC, n = 5) and 3 (HER2neu-/EGFR+, n = 18), of which 28 patients were eligible (14 per arm). Enrollment was curtailed after announcement of the negative LOGiC trial results. Median PFS was 8.0 versus 5.9 months (HR = 0.86, 95% CI 0.37-1.99) in the per protocol population, and 8.0 versus 6.3 months (HR = 0.85, 95% CI 0.30-2.46) for stratum 3, in the lapatinib versus placebo arm respectively. Median OS was 13.8 versus 10.1 months, respectively (HR = 0.90, 95% CI 0.35-2.27). There were no safety concerns. CONCLUSIONS: Central EGFR and HER2neu stratification by IHC and FISH can be used for further pan-HER strategies. Lapatinib with ECF/X was well tolerated, but did not show clear activity in patients with metastatic GC.

Cytokeratin-18 fragments predict treatment response and overall survival in gastric cancer in a randomized controlled trial.

BACKGROUND: Gastric cancer is common malignancy and exhibits a poor prognosis. At the time of diagnosis, the majority of patients present with metastatic disease which precludes curative treatment. Non-invasive biomarkers which discriminate early from advanced stages or predict the response to treatment are urgently required. This study explored the cytokeratin-18 fragment M30 and full-length cytokeratin-18 M65 in predicting treatment response and survival in a randomized, placebo-controlled trial of advanced gastric cancer. METHODS: Patients enrolled in the SUN-CASE study received sunitinib or placebo as an adjunct to standard therapy with leucovorin (Ca-folinate), 5-fluorouracil, and irinotecan in second or third line. Treatment response rates, progression-free survival and overall survival were assessed during a follow-up period of 12 months. Cytokeratin-18 fragments were analyzed in 52 patients at baseline and day 14 of therapy. RESULTS: Levels of M30 correlated with the presence of metastasis and lymph node involvement and decreased significantly during chemotherapy. Importantly, baseline levels of M30 were significantly higher in patients who failed therapy. In addition, patients who did not respond to treatment were also identifiable at day 14 based on elevated M30 levels. By stepwise regression analysis, M30 at day 14 was identified as independent predictor of treatment response. Likewise, serum levels of full-length cytokeratin-18 M65 at baseline also correlated with treatment failure and progression-free survival. The addition of sunitinib did not exert any effects on serum levels of M30 or M65. CONCLUSION: The cytokeratin-18 fragment M30 at day 14 identifies patients that fail to second- or third-line therapy for advanced gastric cancer. Validation of this non-invasive biomarker in gastric cancer is warranted.

External Validation of the Proposed Kiel Staging System and Comparison with the Old (6th Edition) and the Currently Used (7th Edition) TNM Classification in Gastric Cancer.

BACKGROUND: Despite the announcement of the 8th edition of TNM classification, the 7th edition (2010) is still being used for prognostic assessment in gastric cancer patients. A proposed new staging system (termed as the Kiel proposal) claims to offer a better prognostic stratification. Our objective was to retrospectively evaluate the Kiel proposal and compare it with the 6th and 7th TNM editions on a collected database. METHODS: We retrospectively analyzed gastric cancer patients who had undergone surgical resection without any previous treatment from selected randomized trials and from a cohort of patients operated at the University Hospital of Mainz, Germany. All patients were restaged using the 3 staging systems and overall survival was estimated and compared. RESULTS: A study population of 491 patients was identified. Relevant changes in stage distribution between the 6th and 7th TNM and the Kiel staging systems were observed. The 6th classification appears to display the best discriminatory measures. The Kiel staging system is slightly less prognostic than the TNM editions, but provides clearly separated strata as with the 6th edition. CONCLUSIONS: The Kiel staging system for gastric cancer appears promising in terms of simplicity, predictability and applicability and should be taken into consideration in future TNM revisions.

Last line therapy with sorafenib in colorectal cancer: A retrospective analysis.

AIM: To analyze the efficacy of last line sorafenib treatment in colorectal cancer patients. METHODS: All patients receiving chemotherapy for colorectal cancer in the outpatient clinic of the University of Mainz since 2006 were retrospectively analyzed for last line sorafenib exposure. Charts of identified patients were analyzed for clinic-pathological parameters, like data on gender, age, date of initial diagnosis, UICC stage, number and kind of the pre-therapies, therapy start and end of sorafenib, sorafenib mediated treatment cessation, side effects, response rates, time to progression and overall survival. RESULTS: Ten patients with a median of 3.0 prior chemotherapy lines had received a last line sorafenib therapy either alone (10%) or in combination with 5-fluorouracil derivates (90%). All patients suffered from colorectal cancer stage UICC 4 and were routinely seen in 2-wk intervals in the oncology outpatient clinic. Median duration of treatment was 142.0 d. At 8 wk 80% of patients showed stable disease but we did not observe any remissions. Median time to progression was 140.5 d (4.7 mo), while median overall survival reached 176.5 d. One patient ceased treatment due to side effects. Reason for treatment stop was bleeding complication in one case and non-specified sorafenib intolerance in another case. Due to the retrospective approach we did not further quantify side effects. CONCLUSION: This retrospective analysis encourages further investigation of sorafenib in colorectal cancer last line therapy.

Understanding of headache patterns modification in an emergency department during the economic crisis of Greece.

Very few neurological research is published regarding health effects of global economic crisis. Our aim was to assess the impact of economic recession on frequency and severity of headaches. We also tested if depression, anxiety and experiences associated with crisis, such as unemployment, were reflected in headaches. This is a retrospective observational study in the Emergency setting of tertiary Clinic from 1 January 2008 until 31 December 2009 and from 1 January 2010 until 31 December 2011. Demographic data were collected of 1094 consecutive adult patients with headache. Multinomial logistic regression performed to examine if hospital anxiety depression (HAD), HAD anxiety, experience of serious life events, year of survey had influence on type of headache. The total number of headache cases increased significantly from 2008 to 2011 (p < 0.001). Tension type and medication overuse headaches remained unchanged over time (p > 0.05), while migraines decreased. Secondary and not otherwise specified (NOS) increased significantly (p < 0.05). The most common, overtime, was Tension type headache, followed by migraines (in 2008, 2011) and NOS (2010). Chi square test showed significant correlation between type of headache and year, as well medication type and year (p < 0.05). Common analgesics, the most common medication, increased five times during survey period (77 % 2008 to 87.6 % 2011). Multivariate analysis revealed stronger association for experience serious events with NOS vs. tension type headache [odds ratio (OR) 0.13; 95 % confidence interval (CI) 0.03, 0.7]. This is the first study showing that the prolonged economic crisis affected headache frequency accompanied by a higher use of analgesics.

The count of tender rather than swollen joints correlates with aortic stiffness in patients with rheumatoid arthritis.

BACKGROUND: Patients with rheumatoid arthritis (RA) are at a higher cardiovascular (CV) risk in comparison to the general population. CV risk associates closely with aortic stiffness. Aim of this exploration was therefore to evaluate aortic stiffness in patients with RA and to examine its association with various RA associated parameters as well as with traditional CV risk factors. METHODS: Measurements of carotid-femoral pulse wave velocity (cfPWV) were analyzed retrospectively in 38 RA patients and 25 controls. We investigated the statistical difference between cfPWV values in the two groups. Furthermore, we analyzed the associations of cfPWV with laboratory and clinical RA parameters including Disease Activity Score 28 and its components, rheumatoid factor, cyclic citrullinated peptide antibodies, antinuclear antibodies and RA duration. Finally, we explored the relationship of cfPWV with traditional CV risk factors in the RA group. RESULTS: cfPWV was not significantly higher in RA patients in comparison to controls in an adjusted statistical model for confounding factors [-0.587 95 % CI (-1.38 to 0.201), p = 0.144]. Among RA patients there was a statistically significant correlation of cfPWV with age (rho = 0.544, p = 0.001) and the count of tender joints [0.051 95 % CI (0.008-0.207), p = 0.034]. Finally, C-reactive protein associated only marginally with cfPWV [0.105 95 % CI (-0.410 to 0.003), p = 0.053]. CONCLUSIONS: In RA patients the number of tender, rather than swollen joints correlates with stiffness of the aorta, as measured through cfPWV. Therefore, RA associated joint pain might play a role in the development of aortic stiffness and thus increase CV risk.

Melatonin 4 mg as prophylactic therapy for primary headaches: a pilot study.

There is growing evidence that headaches are connected to melatonin secretion. Our aim was to assess the potential effectiveness of melatonin for primary headache prevention. Forty-nine patients (37 with migraine and 12 with chronic tension-type headache, TTH) were prescribed oral melatonin, 4 mg, 30 minutes before bedtime for six months. Forty-one (83.6%) of the 49 patients completed the study, while eight dropped out for personal reasons. A statistically significant reduction in headache frequency was found between baseline and final follow-up after six months of treatment (p=0.033 for TTH patients and p<0.001 for migraineurs). The Headache Impact Test score was significantly reduced in both groups of headache patients (p=0.002 and p<0.001, respectively). At baseline, melatonin levels, measured both during a headache attack and a pain-free period, did not differ between patients with TTH and migraineurs (p=0.539 and p=0.693, respectively), and no statistically significant differences in Hamilton Depression Rating Scale scores were found between the two groups. This pilot study shows promising results, in terms of headache frequency reduction and daily quality of life improvement, in both groups.