Prognostic value of histopathologic traits independent of stromal tumor-infiltrating lymphocyte levels in chemotherapy-naïve patients with triple-negative breast cancer

Background: In the absence of prognostic biomarkers, most patients with early-stage triple-negative breast cancer (eTNBC) are treated with combination chemotherapy. The identification of biomarkers to select patients for whom treatment de-escalation or escalation could be considered remains an unmet need. We evaluated the prognostic value of histopathologic traits in a unique cohort of young, (neo)adjuvant chemotherapy-naïve patients with early-stage (stage I or II), node-negative TNBC and long-term follow-up, in relation to stromal tumor-infiltrating lymphocytes (sTILs) for which the prognostic value was recently reported. Materials and methods: We studied all 485 patients with node-negative eTNBC from the population-based PARADIGM cohort which selected women aged &lt;40 years diagnosed between 1989 and 2000. None of the patients had received (neo)adjuvant chemotherapy according to standard practice at the time. Associations between histopathologic traits and breast cancer-specific survival (BCSS) were analyzed with Cox proportional hazard models. Results: With a median follow-up of 20.0 years, an independent prognostic value for BCSS was observed for lymphovascular invasion (LVI) [adjusted (adj.) hazard ratio (HR) 2.35, 95% confidence interval (CI) 1.49-3.69], fibrotic focus (adj. HR 1.61, 95% CI 1.09-2.37) and sTILs (per 10% increment adj. HR 0.75, 95% CI 0.69-0.82). In the sTILs &lt;30% subgroup, the presence of LVI resulted in a higher cumulative incidence of breast cancer death (at 20 years, 58%; 95% CI 41% to 72%) compared with when LVI was absent (at 20 years, 32%; 95% CI 26% to 39%). In the ≥75% sTILs subgroup, the presence of LVI might be associated with poor survival (HR 11.45, 95% CI 0.71-182.36, two deaths). We confirm the lack of prognostic value of androgen receptor expression and human epidermal growth factor receptor 2 -low status. Conclusions: sTILs, LVI and fibrotic focus provide independent prognostic information in young women with node-negative eTNBC. Our results are of importance for the selection of patients for de-escalation and escalation trials.</p

Diagnosis of biliary tract and ampullary carcinomas

Diagnostic methods for biliary tract carcinoma and the efficacy of these methods are discussed. Neither definite methods for early diagnosis nor specific markers are available in this disease. When this disease is suspected on the basis of clinical symptoms and risk factors, hemato-biochemical examination and abdominal ultrasonography are performed and, where appropriate, enhanced computed tomography (CT) and/or magnetic resonance cholangiopancreatography (MRCP) is carried out. Diagnoses of extrahepatic bile duct cancer and ampullary carcinoma are often made based on the presence of obstructive jaundice. Although rare, abdominal pain and pyrexia, as well as abnormal findings of the hepatobiliary system detected by hemato-biochemical examination, serve as a clue to making a diagnosis of these diseases. On the other hand, the early diagnosis of gallbladder cancer is scarcely possible on the basis of clinical symptoms, so when this cancer is found with the onset of abdominal pain and jaundice, it is already advanced at the time of detection, thus making a cure difficult. When gallbladder cancer is suspected, enhanced CT is carried out. Multidetector computed tomography (MDCT), in particular — one of the methods of enhanced CT — is useful for decision of surgical criteria, because MDCT shows findings such as localization and extension of the tumor, and the presence or absence of remote metastasis. Procedures such as magnetic resonance imaging, endoscopic ultrasonography, bile duct biopsy, and cholangioscopy should be carried out taking into account indications for these procedures in individual patients. However, direct biliary tract imaging is necessary for making a precise diagnosis of the horizontal extension of bile duct cancer

Flowcharts for the management of biliary tract and ampullary carcinomas

No strategies for the diagnosis and treatment of biliary tract carcinoma have been clearly described. We developed flowcharts for the diagnosis and treatment of biliary tract carcinoma on the basis of the best clinical evidence. Risk factors for bile duct carcinoma are a dilated type of pancreaticobiliary maljunction (PBM) and primary sclerosing cholangitis. A nondilated type of PBM is a risk factor for gallbladder carcinoma. Symptoms that may indicate biliary tract carcinoma are jaundice and pain in the upper right area of the abdomen. The first step of diagnosis is to carry out blood biochemistry tests and ultrasonography (US) of the abdomen. The second step of diagnosis is to find the local extension of the carcinoma by means of computed tomography (CT), magnetic resonance imaging (MRI), magnetic resonance cholangiopancreatography (MRCP), percutaneous transhepatic cholangiography (PTC), and endoscopic retrograde cholangiopancreatography (ERCP). Because resection is the only way to completely cure biliary tract carcinoma, the indications for resection are determined first. In patients with resectable disease, the indications for biliary drainage or portal vein embolization (PVE) are checked. In those with nonresectable disease, biliary stenting, chemotherapy, radiotherapy, and/or best supportive care is selected

Open Innovation in Practice: Goal Complementarity and Closed NPD Networks to Explain Differences in Innovation Performance for SMEs in the Medical Devices Sector

Cooperation with other organizations increases the innovation performance of organization, especially for small and medium-sized enterprises (SMEs) as they encounter liabilities of “smallness” (e.g., limited financial resources, and manpower). In the medical devices sector, collaboration with external partners for NPD becomes increasingly important due to the complexity of the products and the development process. About 80% of companies in this sector are SMEs. These companies operate in a highly regulated sector, which affects the organization of the external network required for the new product development (NPD) process. SMEs are practicing extensively open innovation activities, but in practice face a number of barriers in trying to apply open innovation. This paper examines multiple network characteristics simultaneously in relation to innovation performance and thereby aligns with and builds further on configuration theory. Configuration theory posits that for each set of network characteristics, there exists an ideal set of organizational characteristics that yields superior performance. In this research, the systems approach to fit is used. Fit is high to the extent that an organization is similar to an ideal profile along multiple dimensions. This ideal profile represents the network profile that the 15% highest performing companies use. It is argued that the smaller the distance between the ideal profile and the network profile that is used, the higher the performance.\ud \ud The objective of this research is (1) to examine the relation between the ideal profile and innovation performance and (2) to examine which organization of the network profile is related to high innovation performance. Quantitative survey data (n = 60, response rate 61.9%) form the core of this research. The quantitative results are clarified and have been triangulated with qualitative interview data (n = 50).\ud \ud Our findings suggest the presence of an “ideal” NPD network profile (in terms of goal complementarity, resource complementarity, fairness trust, reliability trust, and network position strength): the more a company's NPD network profile differs from this ideal profile, the lower the innovation performance. In addition, the results of our study indicate that the NPD network profiles of successful and less successful SMEs in the medical devices sector significantly differ in terms of “goal complementarity,” while this is less the case for trust and resource complementarity labeled distinctive by previous research. Finally, results show that a relatively closed, focused, and consistent “business-like” NPD networking approach, which is characterized by result orientation and professionalism, is related to high innovation performance. It is recommended that SMEs in the medical devices sector aiming to distinguish themselves from competitors in terms of innovation performance focus on goal complementarity while adopting such a business-like attitude toward their NPD network partner