Node negative colorectal cancer patients: assesment of high-risk features on recurrence.

BACKGROUND: The introduction of population-based screening programs for colorectal cancer (CRC) results in less patients with advanced disease. There is an increase in the amount of node negative CRC, which makes adequate risk stratification for this particular group of patients necessary. The addition of more risk factors to the conventional histological high-risk factors is investigated in this retrospective study. PATIENTS AND METHODS: A cohort of 227 node negative (stage I and II) CRC patients who were not treated with adjuvant chemotherapy were selected from two previously conducted cohort studies. Detailed histopathological examination was performed by two independent observers and molecular background (BRAF/RAS mutations, microsatellite status (MSI)) was studied. Univariate analyses were used to analyse differences in histological and mutational characteristics between patients with and without recurrence. P-values below 0.05 were considered statistically significant. RESULTS: Poorly differentiated histology (p:0.002), BRAF mutation (p:0.002) and MSI status (p:0.006) were found significant relevant risk factors that were related to recurrent disease. Poorly differentiated histology was associated with intermediate/high tumor budding (TB) (p:0.001), a BRAF mutation (p:0.001) and MSI status (p:0.001). A combination of all three features (poorly differentiated histology, BRAF and MSI) was more often present in the recurrence group. CONCLUSIONS: Recurrence in node negative CRC patients could be better predicted when molecular features such as, BRAF mutation and MSI status are incorporated into a model with poorly differentiated CRC. Therefore, these features might help in the selection of patients who possibly will benefit from adjuvant treatment.

Making medical devices safer: impact of plastic and silicone oil on microbial biofilm formation.

BACKGROUND: Medical devices face the challenge of microbial biofilm attached to the surface. Ultimately, this may jeopardize the function of the device and increase the patient's risk of infection. However, reliable methods to prevent biofilm are lacking. AIM: To investigate the effect of silicone oil-coated polypropylene plastic, used in a new automatic urinometer, on biofilm formation; furthermore, to explore the impact of silicone oil viscosity and compare polypropylene with polystyrene, another common medical plastic. METHODS: Common pathogens, including extended-spectrum beta lactamase (ESBL) -producing and multi-drug-resistant bacteria, as well as Candida albicans, were investigated. Isogenic Escherichia coli strains deficient in the important biofilm forming factors curli, cellulose and type 1 fimbriae (fim D) were used to determine the possible mode of action by silicone oil. Clear flat-bottomed polypropylene or polystyrene wells were pretreated with either low- or medium-viscosity silicone oil and microbes were added. After 72 h, biofilm formation was quantified using crystal violet assay. FINDINGS: Silicone oil-coated polypropylene plastic surfaces, regardless of the oil viscosity, significantly inhibited biofilm formation of all tested Gram-negative and Gram-positive bacteria, including ESBL-producing and multi-drug resistant strains, as well as C. albicans. Silicone oil did not affect bacterial or candida growth and curli fimbriae were found to be the main target of silicone oil. Polypropylene plastic itself without oil had a better effect in preventing biofilm formation than polystyrene. CONCLUSION: These findings suggest a new strategy to decrease microbial biofilm formation, which may reduce hospital-acquired infections and prevent dysfunction of medical devices.

Measurement of anti-TSH receptor antibodies: what is the correct cut-off value?

BACKGROUND: Autoantibodies against the thyroid stimulating hormone receptor, thyrotropin receptor autoantibodies (TRAb) are diagnostic for Graves' disease and can be measured by different methods. As antibody concentrations are not comparable between methods, appropriate cut-off values need to be established for every single method. For a third-generation TRAb assay (Phadia, Thermofisher), the manufacturer determined the cut-off value in a study population consisting of Graves' disease (both newly diagnosed and patients under treatment) and non-Graves' disease patients. The aim of this study was to verify whether this cut-off value holds true in our population. METHODS: Retrospective analysis was performed on TRAb measurements collected over a period of six months from all patients referred for TRAb testing. For our study, we included patients that were newly diagnosed with hyperthyroidism including Graves' disease, multinodular goitre, toxic adenoma, and thyroiditis. Furthermore, we included Graves' patients that were under treatment at the time of TRAb measurement. RESULTS: Whereas all patients with Graves' disease had positive TRAb, few patients with multinodular goitre, toxic adenoma, and thyroiditis scored positive for TRAb. ROC curve analysis revealed a cut-off value of 4.5 IU/l (compared to 3.3 IU/l established by the manufacturer). Newly diagnosed Graves' patients had higher TRAb concentrations compared to patients under treatment. CONCLUSION: The cut-off value of this immunoassay should probably be set higher in untreated Graves' patients than proposed by the manufacturer as the cut-off value should be determined in a study population excluding Graves' patients under treatment. The overall clinical picture remains crucial in the diagnosis of Graves' disease.

Convective-Dispersion Modeling in 3D Contrast-Ultrasound Imaging for the Localization of Prostate Cancer.

Despite being the solid tumor with the highest incidence in western men, prostate cancer (PCa) still lacks reliable imaging solutions that can overcome the need for systematic biopsies. Dynamic contrast-enhanced ultrasound imaging (DCE-US) allows us to quantitatively characterize the vascular bed in the prostate, due to its ability to visualize an intravenously administered bolus of contrast agents. Previous research has demonstrated that DCE-US parameters related to the vascular architecture are useful markers for the localization of PCa lesions. In this paper, we propose a novel method to assess the convective dispersion (D) and velocity (v) of the contrast bolus spreading through the prostate from three-dimensional (3D) DCE-US recordings. By assuming that D and v are locally constant, we solve the convective-dispersion equation by minimizing the corresponding regularized least-squares problem. 3D multiparametric maps of D and v were compared with 3D histopathology retrieved from the radical prostatectomy specimens of six patients. With a pixel-wise area under the receiver operating characteristic curve of 0.72 and 0.80, respectively, the method shows diagnostic value for the localization of PCa.

Thyrotoxic periodic paralysis: an unusual presentation of hyperthyroidism.

Thyrotoxic periodic paralysis (TPP) is a complication of hyperthyroidism among Asians, characterised by sudden onset of hypokalaemia and muscle paralysis. Several factors may contribute to a delay in diagnosis, including the subtlety of hyperthyroidism, the transient nature of the events and the rarity of this disease in the West. As life-threatening arrhythmias may occur during an attack, awareness among physicians is necessary for early recognition and treatment. Advances have been made in understanding the pathophysiological mechanism leading to hypokalaemia, which include recently identified mutations of the inwardly rectifying potassium channel Kir2.6. Treatment includes the supplementation of potassium, a nonselective beta-blocker, and ultimately treatment of the underlying hyperthyroidism. Here we report three cases of TPP in the Netherlands, and review the literature on clinical features, pathophysiological hypothesis and treatment.

High-risk human papillomavirus detection in self-sampling compared to physician-taken smear in a responder population of the Dutch cervical screening: Results of the VERA study.

In 2017 the cervical cancer screening program in The Netherlands will be revised. Cervical smears will primarily be tested for the presence of high-risk human papillomavirus (hrHPV) instead of cytology, and vaginal self-sampling will be offered to non-responders. This includes a potential risk that part of the women who would otherwise opt for a cervical smear will wait for self-sampling. However, self-sampling for hrHPV in a responder population has never been studied yet. The aim of this study was to investigate the applicability and accuracy of self-sampling in detecting hrHPV in a screening responder population. A total of 2049 women, aged 30-60years, participating in the screening program in The Netherlands were included from April 2013 to May 2015. After they had their cervical smear taken, women self-collected a cervicovaginal sample with a brush-based device, the Evalyn Brush. Both the cervical smear and self-sample specimen were tested with the COBAS 4800 HPV platform. The hrHPV prevalence was 8.0% (95% CI 6.9-9.2) among the physician-taken samples, and 10.0% (95% CI 8.7-11.3) among the self-samples. There was 96.8% (95% CI 96.0-97.5) concordance of hrHPV prevalence between self-samples and physician-taken samples. Women in our study evaluated self-sampling as convenient (97.1%), user-friendly (98.5%), and 62.8% preferred self-sampling over a physician-taken sampling for the next screening round. In conclusion, self-sampling showed high concordance with physician-taken sampling for hrHPV detection in a responder screening population and highly acceptable to women. Implementation of HPV-self-sampling for the responder population as a primary screening tool may be considered.

Prognostic implications of occult nodal tumour cells in stage I and II colon cancer: The correlation between micrometastasis and disease recurrence.

INTRODUCTION: Occult nodal tumour cells should be categorised as micrometastasis (MMs) and isolated tumour cells (ITCs). A recent meta-analysis demonstrated that MMs, but not ITCs, are prognostic for disease recurrence in patients with stage I/II colon cancer. AIMS & METHODS: The objective of this retrospective multicenter study was to correlate MMs and ITCs to characteristics of the primary tumour, and to determine their prognostic value in patients with stage I/II colon cancer. RESULTS: One hundred ninety two patients were included in the study with a median follow up of 46 month (IQR 33-81 months). MMs were found in eight patients (4.2%), ITCs in 37 (19.3%) and occult tumour cells were absent in 147 patients (76.6%). Between these groups, tumour differentiation and venous or lymphatic invasion was equally distributed. Advanced stage (pT3/pT4) was found in 66.0% of patients without occult tumour cells (97/147), 72.9% of patients with ITCs (27/37), and 100% in patients with MMs (8/8), although this was a non-significant trend. Patients with MMs showed a significantly reduced 3 year-disease free survival compared to patients with ITCs or patients without occult tumour cells (75.0% versus 88.0% and 94.8%, respectively, p = 0.005). When adjusted for T-stage, MMs independently predicted recurrence of cancer (OR 7.6 95% CI 1.5-37.4, p = 0.012). CONCLUSION: In this study, the incidence of MMs and ITCs in patients with stage I/II colon cancer was 4.2% and 19.3%, respectively. MMs were associated with an reduced 3 year disease free survival rate, but ITCs were not.

Carbon dioxide insufflation deflects airborne particles from an open surgical wound model.

BACKGROUND: Surgical site infections remain a significant burden on healthcare systems and may benefit from new countermeasures. AIM: To assess the merits of open surgical wound CO2 insufflation via a gas diffuser to reduce airborne contamination, and to determine the distribution of CO2 in and over a wound. METHODS: An experimental approach with engineers and clinical researchers was employed to measure the gas flow pattern and motion of airborne particles in a model of an open surgical wound in a simulated theatre setting. Laser-illuminated flow visualizations were performed and the degree of protection was quantified by collecting and characterizing particles deposited in and outside the wound cavity. FINDINGS: The average number of particles entering the wound with a diameter of <5µm was reduced 1000-fold with 10L/min CO2 insufflation. Larger and heavier particles had a greater penetration potential and were reduced by a factor of 20. The degree of protection was found to be unaffected by exaggerated movements of hands in and out of the wound cavity. The steady-state CO2 concentration within the majority of the wound cavity was >95% and diminished rapidly above the wound to an atmospheric level (∼0%) at a height of 25mm. CONCLUSION: Airborne particles were deflected from entering the wound by the CO2 in the cavity akin to a protective barrier. Insufflation of CO2 may be an effective means of reducing intraoperative infection rates in open surgeries.

Investigating screening for diabetes in women with a history of gestational diabetes.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is encountered more frequently in women with a history of gestational diabetes (GD). Screening for T2DM after pregnancy is, therefore, recommended every ≥ 1-3 years in this population. Early detection could allow for timely intervention strategies, especially in women of childbearing age. Data on adherence to diabetes screening recommendations and the prevalence of T2DM in this population are not available in the Dutch population. AIM: To investigate the T2DM screening rate and evaluate the risk of T2DM in the five-year period following GD pregnancy. METHODS: Single-centre survey in 85 women diagnosed with GD in 2010, using electronic medical records. Primary care physicians were asked to complete a survey regarding the screening frequency and the onset of T2DM in the five-year period following the GD pregnancy. RESULTS: On average 33% underwent yearly screening. The screening rate, however, went up to 61.2% after primary care physicians were requested to screen this population in 2015. Of the women who were screened, 10 (19.2%) developed T2DM within five years after GD. CONCLUSION: Current screening recommendations are poorly met, leading to missed, or delayed diagnosis of T2DM in our population. T2DM is a frequently occurring long-term complication in those who were screened in the five-year period after delivery. Optimising awareness amongst health care professionals of GD as a risk factor for T2DM is warranted and strategies to improve surveillance are necessary.

Relation of intraoperative temperature to postoperative mortality in open colon surgery--an analysis of two randomized controlled trials.

INTRODUCTION: The open surgical wound is exposed to cold and dry ambient air resulting in heat loss mainly through radiation and convection. This cools the wound and promotes local vasoconstriction and hypoxia. Carbon dioxide (CO2) and water vapor are greenhouse gases with a warming effect. The aim was to evaluate if warm humidified CO2 insufflated in surgical wound can affect long-term overall mortality METHODS: This is a retrospective study of two clinical trials, where patients were randomized to warm humidified CO2 (n = 80) or not (n = 78). All patients underwent elective major open colon surgery. Patients in the treatment group received insufflation of warm humidified CO2 into the open wound cavity via a gas diffuser to create a local atmosphere of 100% CO2. Temperature in the wound cavity was measured with a heat-sensitive infrared camera. Core temperature was measured at the tympanic membrane. Median follow-up was 70.9 months. RESULTS: A multivariate analysis adjusted for age (p = 0.001) and cancer (p = 0.165) showed that the larger the temperature difference between final core temperature and wound edge temperature, the lower the overall survival rate (p = 0.050). Patients receiving insufflation of warm humidified CO2 had a tendency to a better overall survival compared with control patients (p = 0.508). End-of-operation wound edge temperature was negatively associated with mortality (OR = 0.80, 95% CI = 0.68-0.95, p = 0.011), whereas mortality was positively associated with age (10-year increase, OR = 1.78, 95% CI = 1.37-2.33, p < 0.001) and cancer (OR = 8.1, 95% CI = 1.95-33.7, p = 0.004). CONCLUSIONS: A small end-of-operation temperature difference between final core and wound edge temperature was positively associated with patient survival in open colon surgery.

Prospective multicenter international surveillance of azole resistance in Aspergillus fumigatus.

To investigate azole resistance in clinical Aspergillus isolates, we conducted prospective multicenter international surveillance. A total of 3,788 Aspergillus isolates were screened in 22 centers from 19 countries. Azole-resistant A. fumigatus was more frequently found (3.2% prevalence) than previously acknowledged, causing resistant invasive and noninvasive aspergillosis and severely compromising clinical use of azoles.

Epidural analgesia associated with better survival in colon cancer.

PURPOSE: Surgery remains the mainstay of treatment for potentially curable colon cancer. Otherwise, the surgical stress response might increase the likelihood of cancer dissemination during and after cancer surgery. There is growing evidence that the type of anaesthesia during cancer surgery plays a role in the metastatic process. Therefore, we assessed if the method of anaesthesia is associated with long-term survival after colon cancer surgery. METHOD: A retrospective single-centre study was conducted including 588 patients who underwent colorectal cancer surgery, TNM stage I-IV, in the Jeroen Bosch Hospital between 1995 and 2003. The Cox proportional hazard model was used for statistical analysis. Adjustments were made for age, sex, comorbidity, TNM stage, chemotherapy, emergency surgery status and year of incidence. RESULTS: Of the 588 primary colon cancer patients with a median age of 70 years, 399 (68 %) patients underwent colon surgery with epidural anaesthesia, whilst 189 (32 %) patients were operated without epidural anaesthesia. Five-year survival for patients not receiving epidural analgesia was 42 % versus 51 % for patients receiving epidural analgesia (p = 0.03). This effect remained after adjustment for relevant patient, tumour, and treatment characteristics (hazard ratio (HR) 1.30 (95 % confidence interval (CI) 1.05-1.59), p = 0.01). Subgroup analysis in patients of 80 years and older (n = 100) showed also a better overall survival after receiving epidural analgesia (HR 1.74 (95 % CI 1.11-2.72), p = 0.01). CONCLUSION: Epidural analgesia during colon cancer surgery was associated with a better overall survival. Prospective trials evaluating the effects of locoregional analgesia on colon cancer recurrence are warranted.

Electromagnetic fields do not affect bone micro-architecture in osteoporotic rats.

OBJECTIVES: Electromagnetic fields (EMF) are widely used in musculoskeletal disorders. There are indications that EMF might also be effective in the treatment of osteoporosis. To justify clinical follow-up experiments, we examined the effects of EMF on bone micro-architectural changes in osteoporotic and healthy rats. Moreover, we tested the effects of EMF on fracture healing. METHODS: EMF (20 Gauss) was examined in rats (aged 20 weeks), which underwent an ovariectomy (OVX; n = 8) or sham-ovariectomy (sham-OVX; n = 8). As a putative positive control, all rats received bilateral fibular osteotomies to examine the effects on fracture healing. Treatment was applied to one proximal lower leg (three hours a day, five days a week); the lower leg was not treated and served as a control. Bone architectural changes of the proximal tibia and bone formation around the osteotomy were evaluated using in vivo microCT scans at start of treatment and after three and six weeks. RESULTS: In both OVX and sham-OVX groups, EMF did not result in cancellous or cortical bone changes during follow-up. Moreover, EMF did not affect the amount of mineralised callus volume around the fibular osteotomy. CONCLUSIONS: In this study we were unable to reproduce the strong beneficial findings reported by others. This might indicate that EMF treatment is very sensitive to the specific set-up, which would be a serious hindrance for clinical use. No evidence was found that EMF treatment can influence bone mass for the benefit of osteoporotic patients. Cite this article: Bone Joint Res 2014;3:230-5.

The diagnostic value of one-step nucleic acid amplification (OSNA) for sentinel lymph nodes in colon cancer patients.

BACKGROUND: Lymph node status in colon cancer is critical for prognosis estimation and treatment allocation. The purpose of this study was to compare the performance of one-step nucleic acid amplification (OSNA) through detection of cytokeratin 19 mRNA levels with routine pathological examination (RP) and multilevel fine pathological examination (FP) in sentinel lymph nodes (SLN), detected using the ex vivo SLN mapping (SLNM) procedure, in presurgically defined nonmetastatic colon cancer patients. METHODS: In this prospective study, 325 SLNs of 128 patients from the Jeroen Bosch Hospital in 's-Hertogenbosch and the Leiden University Medical Center were investigated by RP (H&E), FP (H&E and Keratin Pan immunohistochemical staining), and OSNA. The SLNs were harvested by the SLNM procedure, using Patent blue or Indocyanine green. SLNs were divided and separate parts were used for RP, FP, and the OSNA assay. RESULTS: The diagnostic value of OSNA was 82.1 and 100 % for both FP and combined method (OSNA and FP) compared with RP. An upstaging rate of 20.2 % was obtained with the use of OSNA only and 36.4 % with the use of FP only. An upstaging rate of 46.5 % was obtained by combining the two methods together. CONCLUSIONS: OSNA and FP appeared to be promising tools for the detection of lymph node micro- and macrometastases in SLNs after SLNM. The performances of OSNA and FP in this study were superior to RP. Because OSNA allows analysis of the whole lymph node, sampling bias can be avoided. OSNA therefore may improve tumor staging.

Lymph node metastasis after a soft tissue sarcoma of the leg: a case report and a review of the literature.

Introduction. Soft tissue sarcomas (STSs) represent 1 percent of all adult malignancies and sarcomas only rarely spread to the regional lymph nodes. Case Presentation. We present a case of a woman with a dermatofibrosarcoma protuberans and a sarcoma not therwise specified of the lower extremity. The patient had no distant metastasis during follow-up, but did develop a regional lymph nodemetastasis (RLNM) in the groin. We reviewed the literature about RLNM in STSs. Discussion. Reviewing the literature we see that within specific histological types RLNM occurs as often as distant metastasis. Furthermore RLNM occurs in over 10% for specific histological types and in 24% of all patients with a soft tissue sarcoma of the lower extremity. Except for radical lymphadenectomy with a 5-year survival rate of 46% there is no appropriate treatment. Conclusion. The risk for a RLNM in certain histological types and anatomical locations might transcend the risk for a distant lung metastasis.

Ultrasound-guided radiofrequency ablation of early breast cancer in a resection specimen: lessons for further research.

PURPOSE: To assess the feasibility and effectiveness of radiofrequency ablation (RFA) in breast cancer, using different histopathologic staining methods to evaluate tissue viability. MATERIALS AND METHODS: In twenty patients with unifocal small (≤1, 5 cm) invasive ductal carcinoma, ultrasound-guided RFA was performed immediately after surgery. Cell viability was assessed using cytokeratin 8 (CK 8) and nicotinamide adenine dinucleotide diaphorase (NADHD) in addition to hematoxylin-eosin (HE). RESULTS: At histopathological examination, ex vivo RFA resulted in complete cell death of the target lesion in 17/20 patients. In two cases viable ductal carcinoma in situ (DCIS) was found just outside the completely ablated lesion. CONCLUSION: RFA of small invasive breast cancer seems to be a feasible treatment option. Both NADHD and CK 8 demonstrate a clear and comparable demarcation between viable and non-viable tissue. A high level of accuracy is required in proper positioning of the needle electrode and a "hot retraction" is mandatory.

Protocolised inpatient care of diabetes mellitus.

BACKGROUND: The prevalence of hyperglycaemia in patients with diabetes mellitus at admission is high. Prevention and treatment is important to prevent further clinical complications. We have conducted a study evaluating implementation of a new protocol to standardise inpatient care of patients with diabetes mellitus. METHODS: A retrospective study including all glucose measurements of adult patients with diabetes mellitus type 1 o r 2 , admitted to a surgery department, was performed before and after implementation of the new protocol. This protocol included direct consultation of an internist and diabetes specialist nurse at admission, who initiated a daily treatment program and adjustment scheme based on glucose measurements four times a day by the HemoCue201DM glucose point of care device. We compared the prevalence of hyperglycaemia and hypoglycaemia before and after implementation with logistic regression analyses adjusted for age and gender. RESULTS: Overall, 360 patients with diabetes mellitus type 1 or 2 with 5322 glucose measurements were included. The risk of developing hyperglycaemia was significantly reduced after implementation of the protocol (22 patients with 65 hyperglycaemias) compared with before the intervention (70 patients with 417 hyperglycaemias) (RR adjusted 0.24 (95% confidence interval 0.19; 0.32)). Overall, 45 patients experienced 95 episodes of hypoglycaemia, which did not differ significantly between the two groups. CONCLUSION: After implementation of a new protocol to standardise inpatient care of diabetes mellitus we established a decrease in the risk to develop hyperglycaemia of 76% without an increased risk of developing hypoglycaemia. Implementation of this protocol required frequent glucose measurements which are facilitated by point of care glucose measurements.