Clinically decisive (dis)agreement in multidisciplinary team assessment of esophageal squamous cell carcinoma; a prospective, national, multicenter study.

BACKGROUND: Decisions regarding tumor staging, operability, resectability, and treatment strategy in patients with esophageal cancer are made at multidisciplinary team (MDT) conferences. We aimed to assess interobserver agreement from four national MDT conferences and whether this would have a clinical impact. METHODS: A total of 20 patients with esophageal cancer were included across all four upper gastrointestinal (GI) cancer centers. Fully anonymized patient data were distributed among the MDT conferences which decided on TNM category, resectability, operability, curability, and treatment strategy blinded to each other's decisions. The interobserver agreement was expressed as both the raw observer agreement and with Krippendorff's α values. Finally, a case-by-case evaluation was performed to determine if disagreement would have had a clinical impact. RESULTS: A total of 80 MDT evaluations were available for analysis. A moderate to near-perfect observer agreement of 79.2%, 55.8%, and 82.5% for TNM category was observed, respectively. Substantial agreement for resectability and moderate agreement for curability were found. However, an only fair agreement was observed for the operability category. The treatment strategies had a slight agreement which corresponded to disagreement having a clinical impact in 12 patients. CONCLUSIONS: Esophageal cancer MDT conferences had an acceptable interobserver agreement on resectability and TM categories; however, the operability assessment had a high level of disagreement. Consequently, the agreement on treatment strategy was reduced with a potential clinical impact. In future MDT conferences, emphasis should be on prioritizing the relevant information being readily available (operability, T & M categories) to minimize the risk of disagreement in the assessments and treatment strategies, and thus, delayed or suboptimal treatment.

Prevalence of venous thromboembolism at diagnosis of upper gastrointestinal cancer.

BACKGROUND: Venous thromboembolism (VTE) in patients with upper gastrointestinal (GI) cancer increases morbidity and mortality. This study aimed to determine the prevalence of VTE at diagnosis of upper GI cancer. METHODS: Patients admitted between February 2008 and February 2011 with upper GI cancer (pancreatic, extrahepatic biliary, lower oesophageal, gastro-oesophageal junction or gastric cancer) were investigated in a cross-sectional cohort study. At cancer diagnosis, all patients were examined for deep vein thrombosis (DVT) by means of bilateral compression ultrasonography. From February 2009 and onwards, computed tomographic pulmonary angiography (CTPA) was also performed for the diagnosis of pulmonary embolism (PE). RESULTS: Some 250 patients had ultrasonography; CTPA was performed in 143 patients on admission. DVT was detected in 13 (5·2 per cent) of the 250 patients, eight (3·2 per cent) of whom were asymptomatic. DVT was correlated with tumour location in the pancreaticobiliary tract (odds ratio (OR) 6·27, 95 per cent confidence interval 1·18 to 33·38; P = 0·031) and tumour stage IV (OR 19·34, 2·33 to 160·70; P = 0·006). PE was detected in 11 (7·7 per cent) of 143 patients, eight (5·6 per cent) of whom were asymptomatic. PE embolism was also significantly more common in patients with pancreaticobiliary tract cancer (OR 7·81, 1·28 to 47·62; P = 0·026) and in those with stage IV disease (OR 17·19, 1·83 to 161·50; P = 0·013). CONCLUSION: The prevalence of VTE at cancer diagnosis was significantly higher in patients with pancreaticobiliary tract cancer than in those with other forms of upper GI cancer, and in patients with advanced cancer stage.

Venous thrombosis in pancreaticobiliary tract cancer: outcome and prognostic factors.

BACKGROUND: The differences in outcome among cancer patients with incidental vs. symptomatic venous thromboembolism (VTE) are unknown. In this study, patients with extrahepatic pancreaticobiliary tract cancer (PBC) were selected for a prospective cohort study between February 2008 and February 2011. METHODS: At the time of cancer diagnosis, all patients were examined for deep vein thrombosis with bilateral compression ultrasonography (biCUS). Computed tomography pulmonary angiography was also performed to diagnose pulmonary embolisms. After inclusion, the patients were followed up with clinical examinations, blood collections, and biCUS. RESULTS: A total of 121 PBC patients were enrolled. At the time of cancer diagnosis, 15 patients had experienced a VTE (12.4%, 95% confidence interval [CI] 7.1-19.6), including six symptomatic and nine incidental cases. A total of 25 first-time VTE events were identified (20.7%; 95% CI 13.8-29.0). Patients with a VTE had reduced survival, with a median overall survival (OS) of 4.4 months (95% CI 2.2-11.5). The median OS of the patients with incidental VTE was 3.0 months (95% CI 0.1-15.0), which was not different from the median OS of the patients with symptomatic VTE (5.0 months; 95% CI 2.1-14.5). The median OS was 11.9 months (95% CI 8.1-14.7) in the PBC patients with no VTEs. CONCLUSION: The occurrence of a VTE event in a PBC patient within the first months of the disease is associated with significantly increased mortality.

[Diagnostic possibilities and strategy in the detection of liver metastases]. / Diagnostiske muligheder og strategi ved påvisning af levermetastaser.

The value of laboratory tests, scintigraphy, angiography, ultrasonography (US), computed tomography (CT) and magnetic resonance imaging (MR) in the detection of hepatic metastases is evaluated through a review of the literature. The diagnostic value, advantages, disadvantages and limitations of each test are discussed separately. The discussion also includes, economic aspects such as costs, time consumption and examination capacity as well as invasiveness, side-effects, use of contrast medium and patient tolerance. Based on an over-all evaluation, high-quality US combined with US-guided needle biopsy is recommended as the first-choice examination in the detection of liver metastases. In cases of doubt, CT with intravenous contrast and CT-guided biopsy are advisable as a supplement to US. For assessing the effect of treatment, CT is the most suited modality because of its reproducibility. In planning a resection of the liver, detailed information about the localization, size and extent of each lesion is required. Under these circumstances a combination of angiography, CT (or MR) and intraoperative US is to be preferred.

[Spontaneously bleeding renal hemangioma treated by embolization]. / Spontant blødende renalt haemangiom behandlet med embolisering.

Until 1990, a total of 198 cases of renal haemangiomas have been reported; these patients often have to undergo partial or total nephrectomy. We report a case of a 37 year old female admitted with severe haematuria. Selective renal angiography revealed a haemangioma with arteriovenous shunting, situated centrally in her left kidney. Embolization of the artery supplying the shunt was performed with five coils, and four months later isotope renography showed that both kidneys were functioning equally well. The only observed side-effect was mild hypertension.

[Intracranial lipomas]. / Intrakranielle lipomer.

Intracranial lipomas are rare lesions that should be regarded as congenital malformations. They are usually asymptomatic and incidental findings during neuroradiological investigations. Other brain malformations are often seen in association with intracranial lipomas. The most common is hypoplasia of the corpus callosum. An attempt at surgical removal is not advisable. Lipomas are strongly adherent to the surroundings and typically enclose both vessels and nerves. Magnetic resonance imaging is capable of differentiating lipomas from dermoid cysts and teratomas, making this the diagnostic method of choice.

[Renal vein thrombosis in the neonatal period]. / Nyrevenetrombose i neonatalperioden.

Renal vein thrombosis is a rare disease, which most often occurs in the newborn, in premature babies with complicated deliveries, dehydration, septicaemia or congenital heart defects or in neonates delivered by diabetic mothers. Renal vein thrombosis is due to venous stasis secondary to haemoconcentration or decreased renal perfusion. The typical features are a palpable flank mass, microscopic haematuria, thrombocytopenia, leucocytosis and fever. Ultrasonographic examination shows an enlarged kidney with decreased echogenicity and loss of corticomedullary differentiation combined with hyperechoic streaks throughout the kidney. In Doppler sonography the obstruction of the peripheral veins causes a missing or even negative diastolic flow in the renal arteries. Intravenous pyelography and CT demonstrate missing or delayed excretion in the enlarged kidney. Usually the affected kidney becomes atrophic with calcifications of the renal parenchyma, the renal vein or the inferior vena cava. Therapy is symptomatic. The prognosis is dependent on the extent of the thrombus. In 25% of cases the affected kidney will improve or regain its normal function.

MRI and PET/CT of patients with bone metastases from breast carcinoma.

3.0Tesla magnetic resonance imaging (MRI) with diffusion-weighted imaging (DWI) was compared with combined 18F-fluorodeoxyglucose positron emission tomography and computed tomography (PET/CT) in patients with suspected bone metastases from breast cancer. A prospective clinical study was performed in 13 female breast cancer patients (mean age 61years; range 45-85 years). The spine was imaged in the sagittal plane with T1-weighted (T1), short tau inversion recovery (STIR), and T2-weighted fat-saturated (T2) sequences. The pelvis was imaged similarly in the coronal plane. Axial DWI was performed from the skull base to the mid-thigh. MRI and PET/CT were performed in all patients at a maximum interval of 10 working days and at least 14 days after chemotherapy. MRI was reviewed by two radiologists, and their consensus on potential metastases in 27 predefined locations was recorded. The predefined locations were the vertebral bodies (24), the left (1) and right (1) pelvic bones, and the sacral bone (1). The PET/CT was reviewed by a radiologists and a nuclear medicine physician. MRI detected 59 of the 60 active metastases found with our gold standard modality PET/CT. T1 had the highest sensitivity (98%) but rather low specificity (77%), but with the addition of STIR and DWI, the specificity increased to 95%. The additional metastases detected with MRI most likely represented postherapeutic residual scars without active tumour. In conclusion, 3.0Tesla MRI with T1, STIR, and DWI is useful for the clinical evaluation of bone metastases from breast cancer and compares well to PET/CT.

Hydralazine-induced changes in tissue perfusion and radiation response in a C3H mammary carcinoma and mouse normal tissues.

Hydralazine has been reported to reduce blood perfusion in tumours, thereby increasing hypoxia and subsequently enhancing tumour sensitivity to certain drugs and hyperthermia. We have investigated the ability of hydralazine to induce such changes in a C3H mouse mammary carcinoma and various normal tissues. In tumours, hydralazine (5 mg/kg; i.v.) modified the radiation response, measured by a local tumour control assay, producing an effect equivalent to that seen in tumours made fully hypoxic by clamping. This effect was time-dependent and correlated with the decrease in tissue perfusion estimated by the 86-RbCl extraction procedure. Similar effects were seen in normal skin, although the changes were less dramatic and of a shorter duration. Hydralazine also reduced 86-RbCl uptake in liver, kidney, gut and spleen, but not in bladder, muscle and lung, suggesting that it may have the potential to increase the sensitivity of some normal tissues to hypoxic cell cytotoxins.

Resistive index: an experimental study of the normal range in the pig.

OBJECTIVES: To study the normal range and distribution of the resistive index (RI) and the resistive index ratio (RIR) in the non-obstructed non-dilated porcine kidney, and to assess the reliability of the threshold values RI 0.70 and RIR 1.10 as prognosticators of true obstruction in the upper urinary tracts. METHODS AND MATERIALS: Twenty female pigs of Danish land race breed were studied under general anaesthesia. Blood pressure and urine output was monitored throughout the experiment. Doppler evaluations were obtained from an interlobar artery in the lower half of each kidney, and the RI was calculated as the average of 3 x 3 cycles for each side independently. Statistical analysis of the obtained results was performed. RESULTS: Forty renal units were studied. The RI values ranged from 0.48-0.85 (mean 0.63). Nine renal units (22.5%) had RI values > or = 0.70. RIR values ranged from 1.00-1.38 (mean 1.07). Three RIR values (15%) were above 1.10. There was no statistically significant relationship between RI and laterality (p = 0.25), and no overall significant relationship between RI and mean arterial blood pressure (r2 = 0.21) or urine output (r2 = 0.004). CONCLUSIONS: This study shows a wide distribution of the RI normal values in the pig model, and our results do not support the normal ranges for RI and RIR, or the cut-off values used in clinical practice.

In vivo assessment of the antiproliferative properties of interferon-alpha during immunotherapy: Ki-67 (MIB-1) in patients with metastatic renal cell carcinoma.

The aim of the present study was to investigate the in vivo antiproliferative effect of interferon alpha (IFN-alpha) in patients with metastatic renal cell carcinoma (mRCC). Core needle biopsies of metastatic and/or the primary kidney cancer were obtained before interleukin-2 (IL-2)- and IFN-alpha-based immunotherapy in 34 patients and repeated after 5 weeks in 25 patients. Tumour proliferation was assessed by use of the anti-Ki-67 antibody MIB-1 and evaluated in multiple, random systematic sampled fields of vision. Ki-67 labelling index (LI) at baseline was median 13.6% (range 1.2-85.0) and median 10.6% (range 1.3-48.6%) at week 5 with a median overall decline of 15.2% (range -95 to +258%) from baseline to week 5. There was no difference between responding and nonresponding patients. Ki-67 LI at week 5 was significantly correlated to survival. Thus, median survival of patients with Ki-67 LI 10.6% (P=0.016). Baseline or change in Ki-67 LI did not correlate to survival. These data suggest that IFN-alpha in vivo has only modest effect on tumour proliferation in patients with mRCC. Tumour Ki-67 (MIB-1) reactivity after 1 month of immunotherapy appears to be a significant predictor of patient survival.

Intratumoural and peripheral blood lymphocyte subsets in patients with metastatic renal cell carcinoma undergoing interleukin-2 based immunotherapy: association to objective response and survival.

The aim of the present study was to analyse lymphocyte subsets in consecutive peripheral blood samples and consecutive tumour tissue core needle biopsies performed before and during interleukin-2 based immunotherapy, and to correlate the findings with objective response and survival. Twenty-six patients with metastatic renal cell carcinoma were treated with low dose s.c. interleukin-2, interferon-alpha and histamine. A total of 250 blood samples and 62 core needle biopsies from 23 and 19 of these patients, respectively, were analysed. After 2 weeks of treatment, a significant positive correlation between absolute number of peripheral blood lymphocytes (P=0.028), CD3 (P=0.017), CD57 (P=0.041) and objective response was demonstrated. There was no correlation between any peripheral blood leukocyte subsets and survival. Cytotoxicity of peripheral blood mononuclear cells was not correlated to objective response or survival. Within the tumour tissue at baseline, a significant positive correlation between CD4 (P=0.027), CD8 (P=0.028), CD57 (P=0.007) and objective response was demonstrated. After one month of immunotherapy, a significant positive correlation between intratumoral CD3 (P=0.026), CD8 (P=0.015), CD57 (P=0.009) and objective response was demonstrated. A significant positive correlation between intratumoral baseline CD4 (P=0.047), baseline CD57 (P=0.035), CD3 at one month (P=0.049) and survival was demonstrated. These data provide novel in vivo evidence of the possible contribution of lymphocyte subsets in the tumour reduction in responding patients during interleukin-2 based immunotherapy. Confirmation of the results requires further studies including a larger number of patients.