Treatment of bulky lymph nodes in locally advanced cervical cancer: boosting versus debulking.

OBJECTIVE: Treatment strategies for bulky lymph nodes in patients with locally advanced cervical cancer scheduled for definitive chemoradiation include nodal boosting with radiotherapy, surgical debulking, or both. The aim of this retrospective cohort study was to compare survival and toxicity in patients receiving these treatments and to compare them with a group that received neither form of treatment. METHODS: Women diagnosed between January 2009 and January 2017 with International Federation of Gynecology and Obstetrics (FIGO) 2009 stage IB2, IIA2-IVA cervical cancer with lymph nodes ≥1.5 cm without upper limit on pretreatment imaging and treated with definitive chemoradiation were selected from the Netherlands Cancer Registry. Patients were categorized by intention-to-treat strategy: boosting, debulking, or neither treatment, with subgroup analysis for patients receiving both treatments, that is, debulking with boosting. Overall and relapse-free survival outcomes were compared by Kaplan-Meier and Cox regression analyses and toxicity by logistic regression analysis. RESULTS: Of 190 patients, 101 (53%) received only nodal boosting, 31 (16%) debulking alone, 29 (15%) debulking combined with boosting, and 29 (15%) received neither treatment. The 5 year overall and relapse-free survival for the treatment groups were 58%, 45% and 45% (p=0.19), and 47%, 44% and 46% (p=0.87), respectively. Multivariable Cox regression analyses demonstrated no differences in overall and relapse-free survival. Combination of debulking with boosting was associated with decreased overall and relapse-free survival compared with debulking alone (HR 2.47, 95% CI 1.22 to 5.00; and HR 2.37, 95% CI 1.14 to 4.93). Nodal boosting was independently associated with a decreased toxicity risk compared with debulking strategy (OR 0.37, 95% CI 0.16 to 0.83). CONCLUSIONS: This study showed no survival benefit from either nodal boosting or debulking strategy in patients with suspicious bulky nodes. Nodal boosting might, however, be associated with less toxicity. Dual treatment with debulking and boosting showed a worse survival outcome because this group probably represents patients with poor prognostic factors.

Safety of mechanical chest compression devices AutoPulse and LUCAS in cardiac arrest: a randomized clinical trial for non-inferiority.

AIMS: Mechanical chest compression (CC) during cardiopulmonary resuscitation (CPR) with AutoPulse or LUCAS devices has not improved survival from cardiac arrest. Cohort studies suggest risk of excess damage. We studied safety of mechanical CC and determined possible excess damage compared with manual CC. METHODS AND RESULTS: This is a randomized non-inferiority safety study. Randomization to AutoPulse, LUCAS, or manual CC with corrective depth and rate feedback was performed. We included patients with in-hospital cardiac arrest or with out-of-hospital cardiac arrest arriving with manual CPR at the emergency department. The primary outcome was serious or life-threatening visceral resuscitation-related damage, assessed blind by post-mortem computed tomography scan and/or autopsy or by clinical course until discharge. Non-inferiority hypothesis: mechanical CC compared with manual control does not increase the primary outcome by a risk difference of > 10% [upper 95% confidence interval (CI)]. We included 115 patients treated with AutoPulse, 122 with LUCAS, and 137 patients received manual CC. Safety outcome analysis was possible in 337 of 374 (90.1%) included patients. The primary outcome was observed in 12 of 103 AutoPulse patients (11.6%), 8 of 108 LUCAS patients (7.4%), and 8 of 126 controls (6.4%). Rate difference AutoPulse-control: +5.3% (95% CI - 2.2% to 12.8%), P = 0.15. Rate difference LUCAS-control +1.0% (95% CI - 5.5% to 7.6%), P = 0.75. CONCLUSION: LUCAS does not cause significantly more serious or life-threatening visceral damage than manual CC. For AutoPulse, significantly more serious or life-threatening visceral damage than manual CC cannot be excluded.

Predicting surgical outcome in patients with International Federation of Gynecology and Obstetrics stage III or IV ovarian cancer using computed tomography: a systematic review of prediction models.

OBJECTIVE: Maximal cytoreduction to no residual disease is an important predictor of prognosis in patients with advanced-stage epithelial ovarian cancer. Preoperative prediction of outcome of surgery should guide treatment decisions, for example, primary debulking or neoadjuvant chemotherapy followed by interval debulking surgery. The objective of this study was to systematically review studies evaluating computed tomography imaging based models predicting the amount of residual tumor after cytoreductive surgery for advanced-stage epithelial ovarian cancer. METHODS: We systematically searched the literature for studies investigating multivariable models that predicted the amount of residual disease after cytoreductive surgery in advanced-stage epithelial ovarian cancer using computed tomography imaging. Detected studies were scored for quality and classified as model derivation or validation studies. We summarized their performance in terms of discrimination when possible. RESULTS: We identified 11 studies that described 13 models. The 4 models that were externally validated all had a poor discriminative capacity (sensitivity, 15%-79%; specificity, 32%-64%). The only internal validated model had an area under the receiver operating characteristic curve of 0.67. Peritoneal thickening, mesenterial and diaphragm disease, and ascites were most often used as predictors in the final models. We did not find studies that assessed the impact of prediction model on outcomes. CONCLUSIONS: Currently, there are no external validated studies with a good predictive performance for residual disease. Studies of better quality are needed, especially studies that focus on predicting any residual disease after surgery.

Losartan reduces aortic dilatation rate in adults with Marfan syndrome: a randomized controlled trial.

AIM: Patients with Marfan syndrome have an increased risk of life-threatening aortic complications, mostly preceded by aortic dilatation. Treatment with losartan, an angiotensin-II receptor-1 blocker, may reduce aortic dilatation rate in Marfan patients. METHODS AND RESULTS: In this multicentre, open-label, randomized controlled trial with blinded assessments, we compared losartan treatment with no additional treatment in operated and unoperated adults with Marfan syndrome. The primary endpoint was aortic dilatation rate at any predefined aortic level after 3 years of follow-up, as determined by magnetic resonance imaging. A total of 233 participants (47% female) underwent randomization to either losartan (n = 116) or no additional treatment (n = 117). Aortic root dilatation rate after 3.1 ± 0.4 years of follow-up was significantly lower in the losartan group than in controls (0.77 ± 1.36 vs. 1.35 ± 1.55 mm, P = 0.014). Aortic dilatation rate in the trajectory beyond the aortic root was not significantly reduced by losartan. In patients with prior aortic root replacement, aortic arch dilatation rate was significantly lower in the losartan group when compared with the control group (0.50 ± 1.26 vs. 1.01 ± 1.31 mm, P = 0.033). No significant differences in separate clinical endpoints or the composite endpoint (aortic dissection, elective aortic surgery, cardiovascular death) between the groups could be demonstrated. CONCLUSION: In adult Marfan patients, losartan treatment reduces aortic root dilatation rate. After aortic root replacement, losartan treatment reduces dilatation rate of the aortic arch.

Severe silent ischaemia detected with an Apple Watch in the home setting: a case report.

Background: The Apple Watch has the capability to record a lead 1 electrocardiogram (ECG) and can identify and report atrial fibrillation. The use for detecting myocardial ischaemia is not endorsed by Apple but is documented in this case. Case summary: A 76-year-old man made a lead 1 ECG with his Apple Watch immediately after exercising on a cross trainer. He was fully asymptomatic. The ECG showed an unusual negative T-wave in this lead 1 that deepened in a few minutes and returned to normal after 22 min. He consulted a cardiologist and a standard exercise ECG confirmed the negative T-wave in lead 1 after maximal exercise and in addition showed widespread ST-depression indicating myocardial ischaemia, again without any clinical symptoms. Further studies revealed severe obstructive three-vessel coronary artery disease that was considered not suitable for percutaneous intervention. A coronary artery bypass operation on all involved vessels was performed successfully. Recovery was uneventful and an exercise ECG repeated 11 weeks later was normal. Discussion: We demonstrated that the lead 1 ECG made with the Apple Watch can reliably record T-wave changes indicating myocardial ischaemia. The use of the Apple Watch to document ischaemic changes should be studied systematically for its potential to identify myocardial ischaemia, mainly triggered by symptoms but maybe for asymptomatic persons as well.

Effect of posture on position of subcutaneous implantable cardioverter-defibrillator.

BACKGROUND: The PRAETORIAN score was developed as an alternative for defibrillation testing after subcutaneous implantable cardioverter-defibrillator implantation to assess 3 aspects of implant position on a bidirectional chest radiograph. The score is validated on a standard standing chest radiograph with arms elevated in the lateral view. OBJECTIVE: We aimed to evaluate the effect of different anatomic positions on the PRAETORIAN score. METHODS: Thirty patients with a subcutaneous implantable cardioverter-defibrillator underwent standard posterior-anterior and lateral chest radiography, including additional lateral views in 2 positions: standing with arms down and supine with arms alongside the body. PRAETORIAN score and weighted κ coefficient were calculated for each position. RESULTS: In 8 of 30 patients, the PRAETORIAN score was ≥90 in standard position. The agreement in PRAETORIAN score was substantial (κ = 0.677) for the position with the arms down and fair (κ = 0.399) for the supine position. With the arms down, the PRAETORIAN score decreased in 10 patients (33%), 4 of whom changed to a lower risk category. In supine position, the PRAETORIAN score decreased in 16 patients (53%), 7 of whom changed to a lower risk category, 1 from high to low risk. CONCLUSION: A supine or arms-down position during chest radiography can result in lower PRAETORIAN scores and underestimation of associated risk on defibrillation testing failure. This emphasizes the importance of correct anatomic positioning (arms up) during chest radiography when the PRAETORIAN score is used.

Diagnostic accuracy of MRI, CT, and [18F]FDG-PET-CT in detecting lymph node metastases in clinically early-stage cervical cancer - a nationwide Dutch cohort study.

OBJECTIVES: Imaging is increasingly used to assess lymph node involvement in clinically early-stage cervical cancer. This retrospective study aimed to evaluate the diagnostic accuracy of MRI, CT, and [18F]FDG-PET-CT. METHODS: Women with International Federation of Gynaecology and Obstetrics (FIGO) 2009 stage IA2-IIA cervical cancer and pretreatment imaging between 2009 and 2017 were selected from the Netherlands Cancer Registry. Patient-based and region-based (i.e. pelvic and common iliac) nodal status was extracted from radiology reports. Pathology results were considered the reference standard for calculating accuracy indices. Multiple imputation was used for missing pathology to limit verification bias risk. RESULTS: Nodal assessment was performed in 1676 patients with MRI, 926 with CT, and 379 with [18F]FDG-PET-CT, with suspicious nodes detected in 17%, 16%, and 48%, respectively. [18F]FDG-PET-CT was used to confirm MRI/CT results in 95% of patients. Pathology results were imputed for 30% of patients. [18F]FDG-PET-CT outperformed MRI and CT in detecting patient-based nodal metastases with sensitivities of 80%, 48%, and 40%, and AUCs of 0.814, 0.706, and 0.667, respectively, but not in specificity: 79%, 92%, and 92%. Region-based analyses showed similar indices in the pelvic region, but worse performance in the common iliac region with AUCs of 0.575, 0.554, and 0.517, respectively. CONCLUSIONS: [18F]FDG-PET-CT outperformed MRI and CT in detecting nodal metastases, which may be related to its use as a verification modality. However, MRI and CT had the highest specificity. As MRI is generally performed routinely to assess local and regional spread of cervical cancer, [18F]FDG-PET-CT can be used to confirm suspicious nodes. CRITICAL RELEVANCE STATEMENT: Accurate assessment of the nodal status in clinically early-stage cervical cancer is essential for tumour staging, treatment decision making and prognosis. KEY POINTS: • The accuracy of MRI, CT or [18F]FDG-PET-CT for nodal staging in early cervical cancer is a subject of discussion. • Overall, [18F]FDG-PET-CT outperformed MRI, followed by CT, when used as a verification modality. • Staging with MRI and the addition of [18F]FDG-PET-CT to verify high-risk cases seems to be a good approach.

Dynamic contrast-enhanced MRI in determining disease activity in perianal fistulizing Crohn disease: a pilot study.

OBJECTIVE: The objective of our study was to perform a semiquantitative analysis of dynamic contrast-enhanced MRI for the evaluation of disease activity and therapeutic response in patients with perianal fistulizing Crohn disease. SUBJECTS AND METHODS: Sixteen consecutively registered patients with perianal Crohn disease underwent pelvic MRI. A dynamic contrast-enhanced sequence was performed at 3 T (temporal resolution, 4.2 seconds) during i.v. contrast injection. Maximum enhancement, initial slope of increase, volume transfer constant (K(trans)), and the extravascular space fractional volume (x028B;(e)) were calculated in a region of interest drawn around the fistula. Perianal disease activity index, C-reactive protein concentration, and an MRI-based activity score were calculated as reference standards. Six patients underwent a second MRI examination 6 weeks after starting treatment with anti-tumor necrosis factor α (anti-TNF-α). RESULTS: Perianal disease activity index moderately correlated with maximum enhancement (r = 0.67, p = 0.005), initial slope of increase (r = 0.58, p = 0.018), and volume of enhancing pixels (r = 0.79, p < 0.001) but not with K(trans) or x028B;(e). Volume of enhancing pixels also correlated with C-reactive protein concentration and the MRI-based score (r = 0.52, p = 0.041; r = 0.79, p < 0.001). The K(trans) values had decreased significantly 6 weeks after the start of anti-TNF-α therapy. CONCLUSION: Maximum enhancement and initial slope of increase correlate with disease activity in perianal Crohn disease. K(trans) may be an indicator of the effect of therapy on patients starting anti-TNF-α treatment.

The negative predictive value of clinical examination with or without anesthesia versus magnetic resonance imaging for parametrial infiltration in cervical cancer stages IB1 to IIA.

OBJECTIVE: This study aimed to compare the negative predictive value (NPV) of clinical examination with or without anesthesia and magnetic resonance imaging (MRI) in identifying patients with cervical carcinoma without parametrial infiltration. METHODS: This retrospective cohort study was conducted at the Academic Medical Center in Amsterdam. The medical files of 203 patients diagnosed with cervical cancer stages IB1-IIA, who underwent surgical treatment between January 1, 2003, and January 31, 2011, were reviewed. We compared clinical International Federation of Gynecology and Obstetrics staging and MRI during the staging procedure. The results were compared with the parametrial status by surgical-pathological investigation, which was considered to be the reference standard. RESULTS: Based on the surgical-pathological findings, 16.7% of the patients treated surgically had parametrial infiltration. For parametrial infiltration, examination under anesthesia (EUA) had an NPV of 65.3% and MRI of 76.9%, respectively. We found no significant difference between these NPVs. CONCLUSIONS: Examination under anesthesia and MRI are equal in identifying cervical cancer patients without parametrial infiltration with a tendency for MRI to perform better than EUA. When outpatient clinical staging is considered inconclusive, pretreatment staging may be limited to MRI. In these cases, EUA seems to have no additional value.

Laparoscopy to predict the result of primary cytoreductive surgery in advanced ovarian cancer patients (LapOvCa-trial): a multicentre randomized controlled study.

BACKGROUND: Standard treatment of advanced ovarian cancer is surgery and chemotherapy. The goal of surgery is to remove all macroscopic tumour, as the amount of residual tumour is the most important prognostic factor for survival. When removal off all tumour is considered not feasible, neoadjuvant chemotherapy (NACT) in combination with interval debulking surgery (IDS) is performed. Current methods of staging are not always accurate in predicting surgical outcome, since approximately 40% of patients will have more than 1 cm residual tumour after primary debulking surgery (PDS). In this study we aim to assess whether adding laparoscopy to the diagnostic work-up of patients suspected of advanced ovarian carcinoma may prevent unsuccessful primary debulking surgery for ovarian cancer. METHODS: Multicentre randomized controlled trial, including all gynaecologic oncologic centres in the Netherlands and their affiliated hospitals. Patients are eligible when they are planned for PDS after conventional staging. Participants are randomized between direct PDS or additional diagnostic laparoscopy. Depending on the result of laparoscopy patients are treated by PDS within three weeks, followed by six courses of platinum based chemotherapy or with NACT and IDS 3-4 weeks after three courses of chemotherapy, followed by another three courses of chemotherapy. Primary outcome measure is the proportion of PDS's leaving more than one centimetre tumour residual in each arm. In total 200 patients will be randomized. Data will be analysed according to intention to treat. DISCUSSION: Patients who have disease considered to be resectable to less than one centimetre should undergo PDS to improve prognosis. However, there is a need for better diagnostic procedures because the current number of debulking surgeries leaving more than one centimetre residual tumour is still high. Laparoscopy before starting treatment for ovarian cancer can be an additional diagnostic tool to predict the outcome of PDS. Despite the absence of strong evidence and despite the possible complications, laparoscopy is already implemented in many countries. We propose a randomized multicentre trial to provide evidence on the effectiveness of laparoscopy before primary surgery for advanced stage ovarian cancer patients. TRIAL REGISTRATION: Netherlands Trial Register number NTR2644.