Efficacy of Preoperative Chemotherapy for High Risk Upper Tract Urothelial Carcinoma.

PURPOSE: The impact of preoperative chemotherapy in patients with upper urinary tract urothelial carcinoma remains poorly investigated. We assessed the rates of pathological complete response (pT0N0/X) and downstaging (pT1N0/X or less) at radical nephroureterectomy after preoperative chemotherapy and evaluated their impact on survival. MATERIALS AND METHODS: This was an international observational study of patients who underwent preoperative chemotherapy and radical nephroureterectomy for high risk upper tract urothelial carcinoma between 2005 and 2017. Multiple imputation of chained equations was applied to account for missing values. Logistic regression analyses were performed to identify predictors of pathological response. Cox proportional hazard regression models were used to estimate recurrence-free survival, cancer specific survival and overall survival. RESULTS: A total of 267 patients met our inclusion criteria. Among included patients 82 (31%) received methotrexate, vinblastine, doxorubicin and cisplatin; 123 (46%) gemcitabine and cisplatin; 25 (9%) gemcitabine and carboplatin; and 32 (12%) other regimens. The overall rates of pathological complete response and pathological downstaging were 10.1% and 44.9%, respectively. On multivariable analysis the use of gemcitabine and cisplatin, and gemcitabine and carboplatin was not statistically different from methotrexate, vinblastine, doxorubicin and cisplatin in achieving pathological complete response and pathological downstaging, respectively. The number of administered cycles did not appear to have an effect on pathological responses. Pathological downstaging was the strongest prognostic factor for recurrence-free survival (HR 0.2, p <0.001), cancer specific survival (HR 0.19, p <0.001) and overall survival (HR 0.40, p <0.001). CONCLUSIONS: Pathological downstaging after preoperative chemotherapy is a robust prognostic factor at radical nephroureterectomy and is associated with improved survival outcomes. Although preoperative chemotherapy appears to be effective, well designed prospective studies are still needed.

[Iatrogenic cecal perforation two days after a caesarian section]. / Een vrouw met buikpijn en braken na een sectio.

A 32-year-old healthy woman was seen two days after a complicated c-section with abdominal pain and vomiting. Inflammatory parameters were high and imaging showed a dilatated colon with intestinal pneumatosis. Surgical exploration showed an iatrogenic perforation of the coecum. Therefore, an ileocecal resection with primary anastomosis was performed. Full recovery occurred two weeks later.

Immediate coiling of a gastroduodenal arterial bleeding in a case of haemorrhagic shock without haematemesis, a case report.

Introduction: and importance: Upper gastrointestinal (GI) bleeding is common in the clinic. In combination with haemorrhagic shock, morbidity is high. Rapid diagnosis and treatment can save lives. With the introduction of precision imaging several treatment options are feasible. Up-to-date diagnosis and treatment requires expertise from interventional radiology, gastroenterology and surgery to form a dedicated intervention team. This is illustrated by a typical case. Case presentation: We report a 78-year-old otherwise healthy male with a severe diverticulum bleeding. He was initially diagnosed with acute pancreatitis. Approximately 60 minutes after CT scanning, he became haemodynamically instable. He also vomited coffee-like fluid but no clear blood or clots. A repeated CT scan showed active bleeding in the retroperitoneal space highly suspicious for a diverticular bleeding just outside the lumen of the duodenum. An acute multidisciplinary intervention team immediately decided not to perform endoscopy (according to the upper GI bleeding guidelines) but to extend the imaging procedure with digital subtraction angiography (DSA). By this time, active bleeding from a side branch of the gastroduodenal artery was noted and successfully coiled. Clinical discussion: Guidelines determine day-to-day management in clinical medicine. Still, there is an exception to every rule. The case presented here was typical of upper GI bleeding with haemodynamic instability and signs of shock, but without haematemesis. This combination indicated a bleeding from somewhere outside the lumen of the GI tract. Instead of endoscopy, the acute intervention team decided to perform CT angiography (CTa) with subsequent DSA. On imaging, the bleeding focus was immediately identified and treated by coiling. Conclusion: Performance of CTa immediately followed by DSA and no endoscopy was decided by an acute intervention team in a patient with upper GI bleeding and haemorrhagic shock. Swift coiling of the bleeding artery outside the GI tract lumen was successful. The team in charge relied on a hybrid multifunctional unit fully equipped to perform interventional radiologic as well as GI procedures.

Novel Classification for Upper Tract Urothelial Carcinoma to Better Risk-stratify Patients Eligible for Kidney-sparing Strategies: An International Collaborative Study.

BACKGROUND: The European Association of Urology risk stratification dichotomizes patients with upper tract urothelial carcinoma (UTUC) into two risk categories. OBJECTIVE: To evaluate the predictive value of a new classification to better risk stratify patients eligible for kidney-sparing surgery (KSS). DESIGN, SETTING, AND PARTICIPANTS: This was a retrospective study including 1214 patients from 21 centers who underwent ureterorenoscopy (URS) with biopsy followed by radical nephroureterectomy (RNU) for nonmetastatic UTUC between 2000 and 2017. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: A multivariate logistic regression analysis identified predictors of muscle invasion (≥pT2) at RNU. The Youden index was used to identify cutoff points. RESULTS AND LIMITATIONS: A total of 811 patients (67%) were male and the median age was 71 yr (interquartile range 63-77). The presence of non-organ-confined disease on preoperative imaging (p < 0.0001), sessile tumor (p < 0.0001), hydronephrosis (p = 0.0003), high-grade cytology (p = 0.0043), or biopsy (p = 0.0174) and higher age at diagnosis (p = 0.029) were independently associated with ≥pT2 at RNU. Tumor size was significantly associated with ≥pT2 disease only in univariate analysis with a cutoff of 2 cm. Tumor size and all significant categorical variables defined the high-risk category. Tumor multifocality and a history of radical cystectomy help to dichotomize between low-risk and intermediate-risk categories. The odds ratio for muscle invasion were 5.5 (95% confidence interval [CI] 1.3-24.0; p = 0.023) for intermediate risk versus low risk, and 12.7 (95% CI 3.0-54.5; p = 0.0006) for high risk versus low risk. Limitations include the retrospective design and selection bias (all patients underwent RNU). CONCLUSIONS: Patients with low-risk UTUC represent ideal candidates for KSS, while some patients with intermediate-risk UTUC may also be considered. This classification needs further prospective validation and may help stratification in clinical trial design. PATIENT SUMMARY: We investigated factors predicting stage 2 or greater cancer of the upper urinary tract at the time of surgery for ureter and kidney removal and designed a new risk stratification. Patients with low or intermediate risk may be eligible for kidney-sparing surgery with close follow-up. Our classification scheme needs further validation based on cancer outcomes.

Iatrogenic caecal perforation two days after a caesarean section, a case report.

INTRODUCTION: and importance: The caesarean section is a widely spread procedure and 29.7 million times performed every year inn 169 countries in the world. Overall, complications are seen in 6% for elective caesarean to 15% for emergency caesarean. CASE PRESENTATION: We here report a case which was initially diagnosed as a postoperative paralytic ileus. After a complicated caesarean section caused by bleeding and problems with haemostasis, a healthy child was born with full mother recovery for the first 24 hours after surgery. Unfortunately, her condition deteriorated between 24 and 48 hours and she reported progressive nausea and painful bloating. Laboratory tests and CT imaging showed progressive signs of inflammation and distention of the caecum and colon. A second CT scan the next day revealed signs of perforation. An ileocecal resection was performed with a primary anastomosis. Full recovery occurred two weeks later. CLINICAL DISCUSSION: With an estimated incidence of only 0,08%, bowel perforations due to caesarean section, are rare. Moreover, is the clinical presentation diverse and computed topography is essential during the diagnostic process. To avoid potential morbidity and mortality, the surgeon must consider performing a laparotomy in case of a deteriorating patient in non-invasive treatment fails. CONCLUSION: Caecal perforation must be considered as complication after a caesarean section. An ileocecal resection is necessary in this situation. This case report shows that a primary anastomosis is a possible option in a healthy patient that is hemodynamically stable during the operation. In case of an unhealthy or hemodynamic unstable patient, the safest option is a temporary ileostomy.

The Performance of Tumor Size as Risk Stratification Parameter in Upper Tract Urothelial Carcinoma (UTUC).

INTRODUCTION: The objective of this study was to evaluate the performance of different tumor diameters for identifying ≥ pT2 upper tract urothelial carcinoma (UTUC) at radical nephroureterectomy. PATIENTS AND METHODS: This was a multi-institutional retrospective study that included 932 patients who underwent radical nephroureterectomy for nonmetastatic UTUC between 2000 and 2016. Tumor sizes were pathologically assessed and categorized into 4 groups: ≤ 1 cm, 1.1 to 2 cm, 2.1 to 3 cm, and > 3 cm. We performed logistic regression and decision-curve analyses. RESULTS: Overall, 45 (4.8%) patients had a tumor size ≤ 1 cm, 141 (15.1%) between 1.1 and 2 cm, 247 (26.5%) between 2.1 and 3 cm, and 499 (53.5%) > 3 cm. In preoperative predictive models that were adjusted for the effects of standard clinicopathologic features, tumor diameters > 2 cm (odds ratio, 2.38; 95% confidence interval, 1.70-3.32; P < .001) and > 3 cm (odds ratio, 1.81; 95% confidence interval, 1.38-2.38; P < .001) were independently associated with ≥ pT2 pathologic staging. The addition of the > 2-cm diameter cutoff improved the area under the curve of the model from 58.8% to 63.0%. Decision-curve analyses demonstrated a clinical net benefit of 0.09 and a net reduction of 8 per 100 patients. CONCLUSION: The 2-cm cutoff appears to be most useful in identifying patients at risk of harboring ≥ pT2 UTUC. This confirms the current European Association of Urology guideline's risk stratification. Tumor size alone is not sufficient for optimal risk stratification, rather a constellation of features is needed to select the best candidate for kidney-sparing surgery.

Pretreatment Risk Stratification for Endoscopic Kidney-sparing Surgery in Upper Tract Urothelial Carcinoma: An International Collaborative Study.

BACKGROUND: Several groups have proposed features to identify low-risk patients who may benefit from endoscopic kidney-sparing surgery in upper tract urothelial carcinoma (UTUC). OBJECTIVE: To evaluate standard risk stratification features, develop an optimal model to identify ≥pT2/N+ stage at radical nephroureterectomy (RNU), and compare it with the existing unvalidated models. DESIGN, SETTING, AND PARTICIPANTS: This was a collaborative retrospective study that included 1214 patients who underwent ureterorenoscopy with biopsy followed by RNU for nonmetastatic UTUC between 2000 and 2017. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We performed multiple imputation of chained equations for missing data and multivariable logistic regression analysis with a stepwise selection algorithm to create the optimal predictive model. The area under the curve and a decision curve analysis were used to compare the models. RESULTS AND LIMITATIONS: Overall, 659 (54.3%) and 555 (45.7%) patients had ≤pT1N0/Nx and ≥pT2/N+ disease, respectively. In the multivariable logistic regression analysis of our model, age (odds ratio [OR] 1.02, 95% confidence interval [CI] 1.0-1.03, p = 0.013), high-grade biopsy (OR 1.81, 95% CI 1.37-2.40, p < 0.001), biopsy cT1+ staging (OR 3.23, 95% CI 1.93-5.41, p < 0.001), preoperative hydronephrosis (OR 1.37 95% CI 1.04-1.80, p = 0.024), tumor size (OR 1.09, 95% CI 1.01-1.17, p = 0.029), invasion on imaging (OR 5.10, 95% CI 3.32-7.81, p < 0.001), and sessile architecture (OR 2.31, 95% CI 1.58-3.36, p < 0.001) were significantly associated with ≥pT2/pN+ disease. Compared with the existing models, our model had the highest performance accuracy (75% vs 66-71%) and an additional clinical net reduction (four per 100 patients). CONCLUSIONS: Our proposed risk-stratification model predicts the risk of harboring ≥pT2/N+ UTUC with reliable accuracy and a clinical net benefit outperforming the current risk-stratification models. PATIENT SUMMARY: We developed a risk stratification model to better identify patients for endoscopic kidney-sparing surgery in upper tract urothelial carcinoma.

[Fracture prevention in metastatic prostate cancer]. / Fractuurpreventie bij androgeendeprivatie-therapie.

Patients with metastatic prostate cancer are living longer than they used to, thanks to a wider range of therapeutic options. This means that an increasing number of men will receive long-term treatment with anti-hormonal therapy - androgen-deprivation therapy (ADT) - and the risk of side effects from this therapy is increasing. A relevant decrease in bone density is increasingly seen in patients receiving ADT, which means that a disproportionate increase in risk of fractures is seen in aging patients. Urologists are confronted with these patients in clinical practice. The question is how urologist-care for these patients is organised in the Netherlands. A survey among urologists in the Netherlands revealed that there is great diversity in how they think and act, and that there is a need for national guidelines and additional training on this subject.

Diagnostic Value of 18F-fluorodeoxyglucose Positron Emission Tomography with Computed Tomography for Lymph Node Staging in Patients with Upper Tract Urothelial Carcinoma.

BACKGROUND: Presence of lymph node metastases (LNM) is an important prognostic factor for cancer-specific survival (CSS) in patients with upper tract urothelial carcinoma (UTUC). In various neoplasms, 18F-fluorodeoxyglucose positron emission tomography with computed tomography (FDG-PET/CT) is an established modality for preoperative lymph node (LN) staging. In UTUC, the diagnostic value of FDG-PET/CT for LN staging is unknown. OBJECTIVE: To determine the diagnostic value of FDG-PET/CT for LN staging in patients with UTUC. DESIGN, SETTING, AND PARTICIPANTS: Data of 152 patients with UTUC who underwent FDG-PET/CT followed by surgical treatment in eight centers between 2007 and 2017 were retrospectively collected. Patients receiving neoadjuvant chemotherapy were excluded. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: FDG-PET/CT results were compared with histopathology after lymph node dissection (LND). Recurrence-free survival (RFS), CSS, and overall survival (OS) were analyzed using Kaplan-Meier estimates, and compared for patients with and without suspicious LNs on FDG-PET/CT. RESULTS AND LIMITATIONS: We included 117 patients, of whom 62 underwent LND. Seventeen patients had LNM at histopathological evaluation. Sensitivity and specificity of FDG-PET/CT for diagnosis of LNM were 82% (95% confidence interval [CI]: 57-96) and 84% (95% CI: 71-94), respectively. RFS was significantly worse in patients with LN-positive FDG-PET/CT than in those with LN-negative FDG-PET/CT (p=0.03). CSS (p=0.11) and OS (p=0.5) were similar between groups. This study is limited by its retrospective design and by its sample size. Our results warrant further validation. CONCLUSIONS: FDG-PET/CT has 82% sensitivity and 84% specificity for the detection of LNM in patients with UTUC. Presence of suspicious LNs on FDG-PET/CT is associated with worse RFS. PATIENT SUMMARY: In patients with upper tract urothelial cancer, positron emission tomography with computed tomography (PET/CT) scans can detect lymph node metastases with noteworthy accuracy. Presence of suspicious lymph nodes on 18F-fluorodeoxyglucose PET/CT is associated with worse recurrence-free survival.