Personal comorbidities and their subsequent risks for liver,gallbladder and bile duct cancers

Many environmental risk factors for hepatobiliary cancers are known but whether they are associated with specific cancer types is unclear. We present here a novel approach of assessing standardized incidence ratios (SIRs) of previously diagnosed comorbidities for hepatocellular carcinoma (HCC), gallbladder cancer (GBC), cholangiocarcinoma (CCA) and ampullary cancer. The 13 comorbidities included alcohol and nonalcohol related liver disease, chronic obstructive pulmonary disease, gallstone disease, viral and other kinds of hepatitis, infection of bile ducts, hepatic and other autoimmune diseases, obesity and diabetes. Patients were identified from the Swedish Inpatient Register from 1987 to 2018, and their cancers were followed from 1997 onwards. SIRs for HCC were 80 to 100 in men and women diagnosed with hepatitis C virus and they were also >10 in patients diagnosed with hepatitis B virus, other kind of hepatitis, hepatic autoimmune disease and nonalcohol related liver disease. Many of these risks, as well as alcohol related liver disease, were either specific to HCC or were shared with intrahepatic CCA. For GBC, CCA and ampullary cancer infection of bile ducts was the main risk factor. Gallstone disease, nonhepatic autoimmune diseases and diabetes were associated with all hepatobiliary cancers. The limitations of the study include inability to cover some rare risk factors and limited follow-up time. Many of the considered comorbidities are characterized by chronic inflammation and/or overt immune disturbance in autoimmune diseases. The results suggest that local chronic inflammation and a related immune disturbance is the carcinogenic trigger for all these cancers.     

Endometriosis and risk of ovarian cancer: what do we know?

Despite long and intensive research, endometriosis remains one of the leading causes of morbidity among premenopausal women. The majority of endometriosis-related ovarian carcinomas occur in the presence of atypical ovarian endometriosis. Nevertheless, despite the increased incidence of ovarian cancer in patients with endometriosis, our knowledge of the risk factors and mechanisms is still incomplete. Narrative overview, synthesizing the recent findings of literature retrieved from databases. Herein, we reviewed and summarized the most recent knowledge regarding endometriosis and ovarian cancer. The evidence showing that patients with endometriosis have a higher risk of developing ovarian cancer is compelling. However, the question of how much higher the absolute risk is, is not fully clear.     

Autoimmune diseases as comorbidities for liver,gallbladder, and biliary duct cancers in Sweden

Background

Autoimmune diseases are associated with many cancers but there is a lack of population-based studies with different autoimmune diseases that have a long follow-up. This is also true of hepatobiliary cancers, which include hepatocellular cancer (HCC) and rarer entities of gallbladder cancer (GBC), intra- and extrahepatic cholangiocarcinoma (iCCA and eCCA), and ampullary cancer.

Methods

Diagnostic data on 43 autoimmune diseases were collected from the Swedish Inpatient Register from 1987 to 2018, and cancer data were derived from the national cancer registry from 1997 onward. Relative risks were expressed as standardized incidence ratios (SIRs).

Results

In a population of 13.6 million, 1.1 million autoimmune diseases were diagnosed and subsequent hepatobiliary cancer was diagnosed in 3191 patients (17.2% of cancers). SIRs for HCC were 2.73 (men) and 2.86 (women), 3.74/1.96 for iCCA, 2.65/1.37 for GBC, 2.38/1.64 for eCCA, and 1.80/1.85 for ampullary cancer. Significant associations between autoimmune disease and HCC were observed for 13 autoimmune diseases, with the highest risks being for autoimmune hepatitis (48.92/73.53, men/women) and primary biliary cirrhosis (38.03/54.48). GBC was increased after six autoimmune diseases, with high SIRs for ulcerative colitis (12.22/3.24) and men with Crohn disease (9.16). These autoimmune diseases were also associated with a high risk of iCCA, which had seven other associations, and eCCA, which had five other associations. Ampullary cancer occurrence was increased after four autoimmune diseases.

Conclusion

An autoimmune disease is a common precursor condition for hepatobiliary cancers. This calls for careful control of autoimmune disease symptoms in each patient and encouragement to practice a healthy lifestyle.     

Paravaginal defect: A new classification of fascial and muscle tears in the paravaginal region

The lateral support of the vaginal wall depends on the integrity of the paravaginal section of the visceral pelvic fascia, levator ani, and their connection. Various defects of the muscle and fascia can result in identical clinical findings—ie, the descent of the lateral vaginal sulcus. In this study, we created a realistic scheme for classifying paravaginal defects, based on the complex relationship of the pelvic fascia with the levator ani. Surgical observations, cadaver examinations, and a complex magnetic resonance imaging (MRI)‐based 3‐dimensional (3D) model were used to analyze the spatial relationships of normal and defective anatomy of the female pelvic floor. Descent of the lateral vaginal sulcus can result from a defect in the paravaginal visceral pelvic fascia, levator ani, or both. The fascial defect can be partial or complete, and the muscle defect can vary in location. A detailed illustrated classification is presented. We present a new model of the pathology that underlies a common clinical finding. Clin. Anat. 29:524–529, 2016. © 2016 Wiley Periodicals, Inc.     

Optimization of the High-Shear Wet Granulation Wetting Process Using Fuzzy Logic Modeling

A fuzzy model has been developed for the optimization of high-shear wet granulation wetting on a plant scale depending on the characteristics of pharmaceutical active substance particles. The model optimized on the basis of experimental data involves a set of rules obtained from expert knowledge and full-scale process data. The skewness coefficient of particle size distribution and the tapped density of the granulated mixture were chosen as the model input variables. The output of the fuzzy ruled system is the optimal quantity of wetting liquid. In comparison to manufacturing practice, a very strong sensitivity of the optimal quantity of the added wetting liquid to the size and shape of the active substance particles has been identified by fuzzy modeling.     

High-resolution melting analysis for detection of MYH9 mutations

May-Hegglin anomaly (MHA), Sebastian (SBS), Fechtner (FTNS) and Epstein (EPS) syndromes are rare autosomal dominant disorders with giant platelets and thrombocytopenia. Other manifestations of these disorders are combinations of the presence of granulocyte inclusions and deafness, cataracts and renal failure. Currently, MHA, SBS, FTNS and EPS are considered to be distinct clinical manifestation of a single illness caused by mutations of the MYH9 gene encoding the heavy chain of non-muscle myosin IIA (NMMHC-IIA). As the MYH9 gene has a high number of exons, it takes much time and material to use this method for the detection of MYH9 mutations. Recently, a new method has been introduced for scanning DNA mutations without the need for direct sequencing: high-resolution melting analysis (HRMA). Mutation detection with HRMA relies on the intercalation of the specific dye (LC Green plus) in double-strand DNA and fluorescence monitoring of PCR product melting profiles. In our study, we optimized the conditions and used HRMA for rapid screening of mutations in all MYH9 exons in seven affected individuals from four unrelated families with suspected MYH9 disorders. Samples identified by HRMA as positive for the mutation were analysed by direct sequencing. HRMA saved us over 85% of redundant sequencing.     

Acute mesenteric ischemia

BACKGROUND/AIMS: Acute mesenteric ischemia (AMI) is a serious disease in old age with low incidence but with a very high mortality rate (60-70%). The etiology is either primary (embolism or thrombosis of mesenteric arteries or veins, non-occlusive mesenteric ischemia) or secondary (mechanical obstruction such as intestinal volvulus, intussusception, tumor-caused compression). Independent of the origin of the illness, the clinical-pathological picture is the same: intestinal ischemia with subsequent necrosis. The aim of this study was to ascertain which underlying conditions lead to increased probability of development of acute mesenteric ischemia. METHODS: Two hundred and fifteen patients with a primary form of AMI were treated in the years 1991-2007, in the 1st Clinic of Surgery in Brno, Czech Republic and in the Department of General Surgery, Derer's University Hospital in Bratislava, Slovak Republic; the results of the treatment have been statistically evaluated. CONCLUSION: The probability of arterial mesenteric ischemia development rises significantly (p < 0.05) in patients with a history of atrial fibrillation and/or myocardial infarction. This probability is also significantly higher in smokers with symptoms of hypertension and clinical signs of abdominal angina (p < 0.05).     

A Method for Evaluation the Fatigue Microcrack Propagation in Human Cortical Bone Using Differential X-ray Computed Tomography

Fatigue initiation and the propagation of microcracks in a cortical bone is an initial phase of damage development that may ultimately lead to the formation of macroscopic fractures and failure of the bone. In this work, a time-resolved high-resolution X-ray micro-computed tomography (CT) was performed to investigate the system of microcracks in a bone sample loaded by a simulated gait cycle. A low-cycle (1000 cycles) fatigue loading in compression with a 900 N peak amplitude and a 0.4 Hz frequency simulating the slow walk for the initialization of the internal damage of the bone was used. An in-house developed laboratory X-ray micro-CT imaging system coupled with a compact loading device were employed for the in situ uni-axial fatigue experiments reaching a 2μm effective voxel size. To reach a comparable quality of the reconstructed 3D images with the SEM microscopy, projection-level corrections and focal spot drift correction were performed prior to the digital volume correlation and evaluation using differential tomography for the identification of the individual microcracks in the microstructure. The microcracks in the intact bone, the crack formation after loading, and the changes in the topology of the microcracks were identified on a volumetric basis in the microstructure of the bone.