External validation of a predictive model of survival after cytoreductive nephrectomy for metastatic renal cell carcinoma.

INTRODUCTION: Recent trials have emphasized the importance of a precise patient selection for cytoreductive nephrectomy (CN). In 2013, a nomogram was developed for pre- and postoperative prediction of the probability of death (PoD) after CN in patients with metastatic renal cell carcinoma. To date, the single-institutional nomogram which included mostly patients from the cytokine era has not been externally validated. Our objective is to validate the predictive model in contemporary patients in the targeted therapy era. METHODS: Multi-institutional European and North American data from patients who underwent CN between 2006 and 2013 were used for external validation. Variables evaluated included preoperative serum albumin and lactate dehydrogenase levels, intraoperative blood transfusions (yes/no) and postoperative pathologic stage (primary tumour and nodes). In addition, patient characteristics and MSKCC risk factors were collected. Using the original calibration indices and quantiles of the distribution of predictions, Kaplan-Meier estimates and calibration plots of observed versus predicted PoD were calculated. For the preoperative model a decision curve analysis (DCA) was performed. RESULTS: Of 1108 patients [median OS of 27 months (95% CI 24.6-29.4)], 536 and 469 patients had full data for the validation of the pre- and postoperative models, respectively. The AUC for the pre- and postoperative model was 0.68 (95% CI 0.62-0.74) and 0.73 (95% CI 0.68-0.78), respectively. In the DCA the preoperative model performs well within threshold survival probabilities of 20-50%. Most important limitation was the retrospective collection of this external validation dataset. CONCLUSIONS: In this external validation, the pre- and postoperative nomograms predicting PoD following CN were well calibrated. Although performance of the preoperative nomogram was lower than in the internal validation, it retains the ability to predict early death after CN

Starreveld scoring method in diagnosing childhood constipation

Four scoring methods exist to assess severity of fecal loading on plain abdominal radiographs in constipated patients (Barr-, Starreveld-, Blethyn- and Leech). So far, the Starreveld score was used only in adult patients. To determine accuracy and intra- and inter-observer agreement of the Starreveld scoring method in the diagnosis of functional constipation among pediatric patients. In addition, we compared the Starreveld with the Barr scoring method. Thirty-four constipated and 34 non-constipated children were included. Abdominal radiographs, obtained before treatment, were rated (Starreveld- and Barr) by 4 observers. A second observation after 4 weeks was done by 3 observers. Cut-off level for the Starreveld score, accuracy as measured by the area under the receiver operator characteristics curve, and inter- and intra-observer agreement were calculated. Cut-off value for the Starreveld score was 10. AUC for Starreveld score was 0.54 and for Barr score 0.38, indicating poor discriminating power. Inter-observer agreement was 0.49-0.52 4 (Starreveld) and 0.44 (Barr), which is considered moderate. Intra-observer agreement was 0.52-0.71 (Starreveld) and 0.62- 0.76 (Barr). The Starreveld scoring method to assess fecal loading on a plain abdominal radiograph is of limited value in the diagnosis of childhood constipatio

The hemostatic system in patients with type 2 diabetes with and without cardiovascular disease

The contribution of the hemostatic system in the development of cardiovascular disease (CVD) in patients with type 2 diabetes is not completely defined. The aim of this study was to elucidate associations of hemostatic factors with the development of CVD in patients with type 2 diabetes. Patients with type 2 diabetes without CVD (n = 113), with CVD (n = 94), and controls without CVD (n = 100) were enrolled in this study. Several hemostatic markers were measured. A disturbed hemostatic balance in patients with type 2 diabetes was observed as illustrated by hypofibrinolysis and increased levels of von Willebrand factor (vWF) and plasminogen-activator inhibitor 1 (PAI-1). Patients with type 2 diabetes with CVD have more thrombin generation compared to patients without CVD. This hemostatic imbalance might contribute to the development of CVD in patients with type 2 diabete

External validation of a predictive model of survival after cytoreductive nephrectomy for metastatic renal cell carcinoma.

INTRODUCTION: Recent trials have emphasized the importance of a precise patient selection for cytoreductive nephrectomy (CN). In 2013, a nomogram was developed for pre- and postoperative prediction of the probability of death (PoD) after CN in patients with metastatic renal cell carcinoma. To date, the single-institutional nomogram which included mostly patients from the cytokine era has not been externally validated. Our objective is to validate the predictive model in contemporary patients in the targeted therapy era. METHODS: Multi-institutional European and North American data from patients who underwent CN between 2006 and 2013 were used for external validation. Variables evaluated included preoperative serum albumin and lactate dehydrogenase levels, intraoperative blood transfusions (yes/no) and postoperative pathologic stage (primary tumour and nodes). In addition, patient characteristics and MSKCC risk factors were collected. Using the original calibration indices and quantiles of the distribution of predictions, Kaplan-Meier estimates and calibration plots of observed versus predicted PoD were calculated. For the preoperative model a decision curve analysis (DCA) was performed. RESULTS: Of 1108 patients [median OS of 27 months (95% CI 24.6-29.4)], 536 and 469 patients had full data for the validation of the pre- and postoperative models, respectively. The AUC for the pre- and postoperative model was 0.68 (95% CI 0.62-0.74) and 0.73 (95% CI 0.68-0.78), respectively. In the DCA the preoperative model performs well within threshold survival probabilities of 20-50%. Most important limitation was the retrospective collection of this external validation dataset. CONCLUSIONS: In this external validation, the pre- and postoperative nomograms predicting PoD following CN were well calibrated. Although performance of the preoperative nomogram was lower than in the internal validation, it retains the ability to predict early death after CN

Topographic distribution of first landing sites of lymphatic metastases from patients with renal cancer

Introduction and Objective: Adjuvant studies with checkpoint inhibitors have attracted new interest in accurate pathological lymph node (LN) staging in renal cell carcinoma. Sentinel lymph node (SN) studies in cN0 patients revealed the pattern of lymphatic radiotracer drainage from renal tumors. The aim of this study was to describe the location of single- or oligometastatic LN and analyze if the topography of these first landing sites matches the drainage pattern observed in SN studies of renal tumors. Materials and Methods: We collected data from 8 referral centers from 1990 to 2018 of all patients with pT1-4 cN0 or cN1 M0 renal cell carcinoma with pathologically confirmed single- or oligometastases in locoregional LN. The location of LN metastases, number, size of metastatic LN, and survival were analyzed using descriptive statistics with SPSS version 22 (IBM, Chicago, IL). Results: From 3,794 patients with histologically confirmed pN1, a total of 76 patients (2%) with single- or oligometastatic pN1 were identified, of whom 24 (31.6%) and 52 (68.4%) were cN0 and cN1, respectively. On the left side, LN metastases were predominantly located in the para-aortal (48.0%; 95% confidence interval [CI] 29.22–63.12%) and hilar (31.42%; 95% CI 17.4–49.4%) area. On the right side, metastases located in retrocaval (26.82%; 95% CI 14.7–43.2%), hilar (26.82%; 95% CI 14.7–43.2%), interaortocaval (26.82%; 95% CI 14.7–43.2%), and paracaval (17.07%; 95% CI 7.6–32.6%) LNs. These landing sites exactly matched the lymphatic drainage pattern of intratumorally injected radiotracer reported in SN studies for both sides. Conclusions: Single- or oligometastatic LNs in renal cancer are mainly located in the hilar, retro-, para, and interaortocaval region on the right side and para-aortal region on the left side. These first landing sites match the drainage pattern reported in SN trials

Lymphatic drainage from renal tumors in vivo: a prospective sentinel node study using SPECT/CT imaging

PURPOSE: Lymphatic drainage from renal tumors is unpredictable and in vivo drainage studies of primary lymphatic landing sites may reveal the variability and dynamics of lymphatic connections. The purpose of this study was to investigate the lymphatic drainage pattern from renal tumors in vivo with SPECT/CT imaging after intra-tumoral radiotracer injection. MATERIALS AND METHODS: We conducted a phase II prospective single-arm study to investigate the distribution of SNs from renal tumors on SPECT/CT imaging. Patients with cT1-3 (<10 cm) cN0M0 renal tumors of any subtype were enrolled. After intra-tumoral ultrasound guided injection of 0.4 ml99mTc-nanocolloid, preoperative imaging of SNs with lymphoscintigraphy and SPECT/CT was performed. SN and locoregional non-SNs were resected using a gamma probe in combination with a mobile gamma camera. The primary study endpoint was location of SNs outside the locoregional retroperitoneal templates (LRT) on SPECT/CT imaging. Using a Simon Minimax two-stage design to detect a 25% extra-LRT location of SNs on imaging with an alpha of 0.05 and a power of 80%, at least 40 patients with SN imaging on SPECT/CT were needed. RESULTS: Sixty-eight patients were included. Forty patients had preoperative SPECT/CT imaging of SNs and were used for primary endpoint analysis. Lymphatic drainage outside the LRT was observed in 14 (35%) patients. Eight patients (20%) had supradiaphragmatic SN. CONCLUSIONS: SNs from renal tumors were mainly located in their respective LRT, but simultaneous SNs located outside the suggested LND templates, including supradiaphragmatic SNs were observed in more than one third of the patients