Summary Background Currently, all patients with vulvar cancer with a positive sentinel node undergo inguinofemoral lymphadenectomy, irrespective of the size of sentinel-node metastases. Our study ...aimed to assess the association between size of sentinel-node metastasis and risk of metastases in non-sentinel nodes, and risk of disease-specific survival in early stage vulvar cancer. Methods In the GROningen INternational Study on Sentinel nodes in Vulvar cancer (GROINSS-V), sentinel-node detection was done in patients with T1–T2 (<4 cm) squamous-cell vulvar cancer, followed by inguinofemoral lymphadenectomy if metastatic disease was identified in the sentinel node, either by routine examination or pathological ultrastaging. For the present study, sentinel nodes were independently reviewed by two pathologists. Findings Metastatic disease was identified in one or more sentinel nodes in 135 (33%) of 403 patients, and 115 (85%) of these patients had inguinofemoral lymphadenectomy. The risk of non-sentinel-node metastases was higher when the sentinel node was found to be positive with routine pathology than with ultrastaging (23 of 85 groins vs three of 56 groins, p=0·001). For this study, 723 sentinel nodes in 260 patients (2·8 sentinel nodes per patient) were reviewed. The proportion of patients with non-sentinel-node metastases increased with size of sentinel-node metastasis: one of 24 patients with individual tumour cells had a non-sentinel-node metastasis; two of 19 with metastases 2 mm or smaller; two of 15 with metastases larger than 2 mm to 5 mm; and ten of 21 with metastases larger than 5 mm. Disease-specific survival for patients with sentinel-node metastases larger than 2 mm was lower than for those with sentinel-node metastases 2 mm or smaller (69·5% vs 94·4%, p=0·001). Interpretation Our data show that the risk of non-sentinel-node metastases increases with size of sentinel-node metastasis. No size cutoff seems to exist below which chances of non-sentinel-node metastases are close to zero. Therefore, all patients with sentinel-node metastases should have additional groin treatment. The prognosis for patients with sentinel-node metastasis larger than 2 mm is poor, and novel treatment regimens should be explored for these patients. Funding None.
To investigate the safety and clinical utility of the sentinel node procedure in early-stage vulvar cancer patients.
A multicenter observational study on sentinel node detection using radioactive ...tracer and blue dye was performed in patients with T1/2 (< 4 cm) squamous cell cancer of the vulva. When the sentinel node was found to be negative at pathologic ultrastaging, inguinofemoral lymphadenectomy was omitted, and the patient was observed with follow-up for 2 years at intervals of every 2 months. Stopping rules were defined for the occurrence of groin recurrences.
From March 2000 until June 2006, a sentinel node procedure was performed in 623 groins of 403 assessable patients. In 259 patients with unifocal vulvar disease and a negative sentinel node (median follow-up time, 35 months), six groin recurrences were diagnosed (2.3%; 95% CI, 0.6% to 5%), and 3-year survival rate was 97% (95% CI, 91% to 99%). Short-term morbidity was decreased in patients after sentinel node dissection only when compared with patients with a positive sentinel node who underwent inguinofemoral lymphadenectomy (wound breakdown in groin: 11.7% v 34.0%, respectively; P < .0001; and cellulitis: 4.5% v 21.3%, respectively; P < .0001). Long-term morbidity also was less frequently observed after removal of only the sentinel node compared with sentinel node removal and inguinofemoral lymphadenectomy (recurrent erysipelas: 0.4% v 16.2%, respectively; P < .0001; and lymphedema of the legs: 1.9% v 25.2%, respectively; P < .0001).
In early-stage vulvar cancer patients with a negative sentinel node, the groin recurrence rate is low, survival is excellent, and treatment-related morbidity is minimal. We suggest that sentinel node dissection, performed by a quality-controlled multidisciplinary team, should be part of the standard treatment in selected patients with early-stage vulvar cancer.
Background
Thyroid nodules are very common in general medical practice, but rarely turn out to be a medullary thyroid carcinoma (MTC). Calcitonin is a sensitive tumour marker for the detection of MTC ...(basal calcitonin). Sometimes a stimulation test is used to improve specificity (stimulated calcitonin). Although the European Thyroid Association's guideline advocates calcitonin determination in people with thyroid nodules, the role of routine calcitonin testing in individuals with thyroid nodules is still questionable.
Objectives
The objective of this review was to determine the diagnostic accuracy of basal and/or stimulated calcitonin as a triage or add‐on test for detection of MTC in people with thyroid nodules.
Search methods
We searched CENTRAL, MEDLINE, Embase and Web of Science from inception to June 2018.
Selection criteria
We included all retrospective and prospective cohort studies in which all participants with thyroid nodules had undergone determination of basal calcitonin levels (and stimulated calcitonin, if performed).
Data collection and analysis
Two review authors independently scanned all retrieved records. We extracted data using a standard data extraction form. We assessed risk of bias and applicability using the QUADAS‐2 tool. Using the hierarchical summary receiver operating characteristic (HSROC) model, we estimated summary curves across different thresholds and also obtained summary estimates of sensitivity and specificity at a common threshold when possible.
Main results
In 16 studies, we identified 72,368 participants with nodular thyroid disease in whom routinely calcitonin testing was performed. All included studies performed the calcitonin test as a triage test. Median prevalence of MTC was 0.32%. Sensitivity in these studies ranged between 83% and 100% and specificity ranged between 94% and 100%.
An important limitation in 15 of the 16 studies (94%) was the absence of adequate reference standards and follow‐up in calcitonin‐negative participants. This resulted in a high risk of bias with regard to flow and timing in the methodological quality assessment.
At the median specificity of 96.6% from the included studies, the estimated sensitivity (95% confidence interval (CI)) from the summary curve was 99.7% ( 68.8% to 100%). For the median prevalence of MTC of 0.23%, the positive predictive value (PPV) for basal calcitonin testing at a threshold of 10 pg/mL was 7.7% (4.9% to 12.1%).
Summary estimates of sensitivity and specificity for the threshold of 10 pg/mL of basal calcitonin testing was 100% (95% CI 99.7 to 100) and 97.2% (95% CI 95.9 to 98.6), respectively. For combined basal and stimulated calcitonin testing, sensitivity ranged between 82% and 100% with specificity between 99% and 100%. The median specificity was 99.8% with an estimated sensitivity of 98.8% (95% CI 65.8 to 100) .
Authors' conclusions
Both basal and combined basal and stimulated calcitonin testing have a high sensitivity and specificity. However, this may be an overestimation due to high risk of bias in the use and choice of reference standard The value of routine testing in patients with thyroid nodules remains questionable, due to the low prevalence, which results in a low PPV of basal calcitonin testing. Whether routine calcitonin testing improves prognosis in MTC patients remains unclear.
The metabolic syndrome may be an important risk factor for cardiovascular disease in long-term survivors of testicular cancer (TC). We investigated the associations between hormone levels and the ...metabolic syndrome in these men.
We included TC patients cured by orchidectomy and cisplatin-based chemotherapy, stage I TC patients after orchidectomy only, and healthy men of comparable age. Presence of the metabolic syndrome was determined using guidelines from the National Cholesterol Education Program Adult Treatment Panel III. Thyroid-stimulating hormone, follicle-stimulating hormone (FSH), inhibin B, luteinizing hormone (LH), total testosterone, sex-hormone-binding globulin, free testosterone, estradiol, dehydroepiandrosterone sulfate, and insulin-like growth factor 1 were determined in blood. Cortisol metabolite excretion was measured in urine.
Eighty-six chemotherapy patients (median follow-up, 7 years) were compared with 44 stage I patients and 47 controls. LH and FSH were higher, and inhibin B and total and free testosterone were lower in chemotherapy patients than controls. Adrenal and thyroid hormone production were unaffected. Chemotherapy patients with the metabolic syndrome (n = 22; 26%) had a higher body mass index (BMI) pretreatment, a larger BMI increase during follow-up, lower total testosterone, and higher urinary cortisol metabolite excretion than those patients without the metabolic syndrome. BMI and insulin were associated with the metabolic syndrome, while total testosterone and urinary cortisol metabolite excretion were associated with BMI.
We found gonadal dysfunction, but normal adrenal and thyroid function. Through its association with BMI, testosterone may play a role in the development of the metabolic syndrome in long-term TC survivors.
Background In multiple endocrine neoplasia type 1 (MEN1), pancreatic neuroendocrine tumors (pNETs) are the leading MEN1-related cause of death. Objective To evaluate EUS and11 C-5-hydroxytryptophan ...positron emission tomography (11 C-5-HTP PET), compared with the recommended screening techniques in MEN1 patients for early detection of pNETs. Design Cross-sectional study. Setting Tertiary-care university medical center. Patients This study involved 41 patients with a proven MEN1 mutation or with one MEN1 manifestation and a mutation carrier as a first-degree family member, with recent screening by abdominal CT or magnetic resonance imaging (MRI) and somatostatin receptor scintigraphy (SRS). Interventions EUS by using a linear Pentax echoendoscope and Hitachi EUB-525 and11 C-5-HTP PET. Main Outcome Measurements Patient-based and lesion-based positivity for pNET was calculated for all imaging techniques. The McNemar test was used to compare the yield of the 4 imaging techniques. Results In 35 of 41 patients, 107 pancreatic lesions were detected in total. EUS detected 101 pancreatic lesions in 34 patients,11 C-5-HTP PET detected 35 lesions in 19 patients, and CT/MRI + SRS detected 32 lesions in 18 patients ( P < .001).11 C-5-HTP PET performed similarly to CT/MRI + SRS and better compared with SRS only (13 lesions in 12 patients), both at a patient-based and lesion-based level ( P < .05). Limitations Single-center study. Conclusion EUS is superior to CT/MRI + SRS for pancreatic lesion detection in patients with MEN1. In this setting,11 C-5-HTP PET is not useful. We recommend EUS as the first-choice pancreas imaging technique in patients with MEN1. (Clinical trial registration number: NTR1668 .)
Most longitudinal studies showed increased relative mortality in individuals with type 2 diabetes mellitus until now. As a result of major changes in treatment regimes over the past years, with more ...stringent goals for metabolic control and cardiovascular risk management, improvement of life expectancy should be expected. In our study, we aimed to assess present-day life expectancy of type 2 diabetes patients in an ongoing cohort study.
We included 973 primary care type 2 diabetes patients in a prospective cohort study, who were all participating in a shared care project in The Netherlands. Vital status was assessed from May 2001 till May 2007. Main outcome measurement was life expectancy assessed by transforming actual survival time to standardised survival time allowing adjustment for the baseline mortality rate of the general population. At baseline, mean age was 66 years, mean HbA(1c) 7.0%. During a median follow-up of 5.4 years, 165 patients died (78 from cardiovascular causes), and 17 patients were lost to follow-up. There were no differences in life expectancy in subjects with type 2 diabetes compared to life expectancy in the general population. In multivariate Cox regression analyses, concentrating on the endpoints 'all-cause' and cardiovascular mortality, a history of cardiovascular disease: hazard ratio (HR) 1.71 (95% confidence interval (CI) 1.23-2.37), and HR 2.59 (95% CI 1.56-4.28); and albuminuria: HR 1.72 (95% CI 1.26-2.35), and HR 1.83 (95% CI 1.17-2.89), respectively, were significant predictors, whereas smoking, HbA(1c), systolic blood pressure and diabetes duration were not.
This study shows a normal life expectancy in a cohort of subjects with type 2 diabetes patients in primary care when compared to the general population. A history of cardiovascular disease and albuminuria, however, increased the risk of a reduction of life expectancy. These results show that, in a shared care environment, a normal life expectancy is achievable in type 2 diabetes patients.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background: Smoking is a remarkable risk factor for inflammatory bowel disease (IBD), aggravating Crohn's disease (CD) while having beneficial effects on ulcerative colitis (UC). We studied the ...effects of active and passive smoking in Dutch IBD patients.
Methods: A questionnaire focusing on cigarette smoke exposure was sent to 820 IBD patients. Returned questionnaires were incorporated into a retrospective chart review, containing details about disease behavior and received therapy.
Results: In all, 675 IBD patients (380 56% CD and 295 44% UC) responded. At diagnosis there were 52% smokers in CD, 41% in the general population, and 28% in UC. The number of present smokers in CD is lower than in the general population (26% versus 35%). No detrimental effects of active smoking on CD were observed, but passive smokers needed immunosuppressants and infliximab more frequently than nonpassive smokers. Active smoking had beneficial effects on UC, indicated by reduced rates of colectomy, primary sclerosing cholangitis, and backwash‐ileitis in active smokers compared to never smokers, and higher daily cigarette dose correlated with less extensive colitis and a lower need for therapy. Furthermore, smoking cessation after diagnosis was detrimental for UC patients, indicated by increased needs for steroids and hospitalizations for patients that stopped smoking after compared to before the diagnosis.
Conclusions: Active smoking is a risk factor for CD, but does not affect the outcome; passive smoking is detrimental for the outcome of CD patients. In UC, active smoking shows dose‐dependent beneficial effects. Our data suggest that passive smoking is a novel risk factor for CD.
(Inflamm Bowel Dis 2009)
Purpose
Evidence accumulates that an active lifestyle positively influences cancer treatment outcome. A “smartphone application” (app) such as “RunKeeper,” to self-monitor physical activity (PA) ...might be helpful. This study aimed to examine whether using RunKeeper to increase self-reported PA is feasible in cancer patients and to evaluate patients’ opinion about using RunKeeper in a 12-week program.
Methods
Adult patients (
n
= 32), diagnosed with cancer, were randomized between usual care (
n
= 16) or a 12-week intervention with instructions to self-monitor PA with RunKeeper (
n
= 16). Changes in PA were determined with the Physical Activity Scale for the Elderly (PASE) at baseline (T0), 6 weeks (T1), and 12 weeks (T2). Usability and patients’ experiences were tested at T2 with the System Usability Scale (SUS) and a semi-structured interview.
Results
Patient mean age was 33.6 years. Between T0 and T1, an increase in PA of 51% (medium estimated effect size
r
= 0.40) was found in PASE sum score in the intervention group compared with usual care. In addition, total minutes of PA increased with 46% (
r
= 0.37). These effects decreased over time (T2). Sedentary time decreased with 19% between T0 and T1 and 27% between T0 and T2. Usability was rated “good” and most patients found RunKeeper use helpful to improve PA.
Conclusions
Self-monitoring PA with RunKeeper was safe and feasible in cancer patients. The RunKeeper use resulted in an increase in PA after 6 weeks. RunKeeper usability was rated good and can be used to study PA in cancer patients.
Trial registration
NCT02391454
Elevated circulating levels of pro-inflammatory biomarkers are associated with adverse health effects, but the extent to which enhanced low-grade inflammation influences remaining life expectancy ...(LE) is uncertain. GlycA is a novel pro-inflammatory marker. We determined effects of GlycA and high sensitivity C-reactive protein (hsCRP) on LE.
GlycA and hsCRP were determined in 5526 subjects. LE was compared in the upper quartile of both GlycA and hsCRP vs. the respective lower three quartiles combined, adjusted for LE of individuals in the Dutch general population of the same birth cohort and sex.
Median follow up was 8.5 years interquartile range 7.9–9.0, during which 348 (6.3%) subjects had deceased. LE at the end of follow up was lower in the highest vs. the lower three quartiles of GlycA (P < .001) and hsCRP (P < .001). Both men as well as women in the highest GlycA quartile had reduced LE vs. the lowest three quartiles combined (P < .001 and P = .02). For hsCRP, this was only observed in men (P < .001) but not in women (P = .67).
This population-based cohort study demonstrates that higher plasma levels of GlycA were associated with reduced LE in men and women. With regard to hsCRP this only applied to men.
•GlycA is a nuclear magnetic resonance spectroscopy-measured glycoprotein biomarker.•GlycA is strongly correlated with hsCRP and related to adverse health effects.•Higher plasma levels of GlycA were associated with reduced life expectancy.
Metastatic rectal cancer patients could benefit from novel therapeutic approaches. The signaling network formed by chemokines and their receptors can promote metastasis and resistance to current ...anticancer treatments. This study assessed the expression of chemokine receptor 4 (CXCR4) and its ligand CXCL12 immuhistochemically in stage IV rectal tumors. Paraffin-embedded primary tumor collected before and after local radiotherapy and systemic treatment with bevacizumab, oxaliplatin and capecitabine was analyzed. Receptor and ligand expression was assessed in the cytoplasm and nucleus of tumor, stromal and normal rectal crypt cells. Baseline expression of CXCR4 and CXCL12 was correlated with patients' pathologic response to treatment. At diagnosis (n=46), 89% of the rectal tumors expressed cytoplasmic CXCR4 and 81% CXCL12. Nuclear CXCR4 expression in tumor cells was present in 30% and nuclear CXCL12 expression in 35% of the tumors. After radiochemotherapy and administration of bevacizumab, nuclear CXCL12 expression was observed in 79% of residual tumors, as compared to 31% of the paired tumor samples expressing nuclear CXCL12 before treatment (P=0.001). There were no differences in CXCR4 or CXCL12 expression at baseline between the patients who had (n=9) and did not have (n=30) a pathologic complete response. Our results show that CXCR4 and CXCL12 are extensively expressed in primary rectal tumors of patients presenting with metastatic disease, while radiochemotherapy and bevacizumab further upregulate CXCL12 expression. These data indicate the importance of the CXCR4/CXCL12 axis in rectal tumor biology, and may suggest the CXCR4/CXCL12 receptor-ligand pair as a potential therapeutic target in metastatic rectal cancer.
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