Violation of onco-surgical principles is associated with survival outcomes in upper tract urothelial carcinomas after radical nephroureterectomy.

OBJECTIVE: Disease recurrence, particularly intravesical recurrence (IVR) after radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC), is common. We investigated whether violations of onco-surgical principles before or during RNU, collectively referred to as surgical violation (SV), were associated with survival outcomes.  Material and methods: Data from a consecutive series of patients who underwent RNU for UTUC 2001-2012 at Skåne University Hospital Lund/Malmö were collected. Preoperative insertion of a nephrostomy tube, opening the urinary tract during surgery or refraining from excising the distal ureter were considered as SVs. Survival outcomes in patients with and without SV (IVR-free [IVRFS], disease-specific [DSS] and overall survival [OS]) were assessed using multivariate Cox regression analyses (adjusted for tumour stage group, prior or concomitant bladder cancer, comorbidity and preoperative urinary cytology). RESULTS: Of 150 patients, 47 (31%) were subjected to at least one SV. Overall, SV was not associated with IVRFS (HR 0.81, 95% CI 0.4-1.6) but with worse DSS (HR 1.9, 95% CI 1.03-3.7) and OS (HR 1.9, 95% CI 1.2-3) in multivariable analysis. Additional analyses with a broader definition of SV including also preoperative instrumentation of the upper urinary tract (ureteroscopy and/or double J stenting) showed similar outcomes for DSS (HR 2.1, 95% CI 1.1-4.3). CONCLUSION: Worse survival outcomes, despite no difference in IVR, for patients that were subjected to the violation of sound onco-surgical principles before or during RNU for UTUC strengthen the notion that adhering to such principles is a cornerstone in upper tract urothelial cancer surgery.

Homozygous factor V Leiden and double heterozygosity for factor V Leiden and prothrombin mutation.

The most common forms of familial thrombophilia are factor V Leiden (FVL) and prothrombin mutation (PTM). Homozygous FVL and PTM have long been feared conditions thought to cause high rates of morbidity and mortality. To analyse clinical features in patients with homozygous FVL and PTM, as well as patients with double heterozygosity for FVL and PTM. All patients with homozygous FVL, PTM or double heterozygosity in the MATS database of 1465 consecutive unselected patients were analysed regarding age at inclusion venous thromboembolism (VTE), age at first thrombosis, recurrence, clinical course and acquired risk factors. We found 36 patients homozygous for FVL. Patients homozygous for FVL were younger than controls at group level (56 ± 18 vs. 63 ± 17, p < 0.02). Homozygous women were younger than female controls (50 ± 19 vs. 63 ± 18, p < 0.002). No difference was observed when comparing male subjects. Women were younger than men at inclusion thrombosis (50 ± 19 vs. 65 ± 14, p < 0.02) and at first thrombosis (47 ± 19 vs. 64 ± 14, p < 0.01). Deep venous thrombosis (DVT) was seen in 33 patients (92 %), 6 (17 %) had pulmonary embolism (PE) and 3 (8 %) had combined DVT and PE. PE was less frequent in homozygous FVL women compared to female controls (p < 0.03). VTE recurred in 3 subjects during the duration of the study. Odds ratio for VTE in homozygous FVL patients compared to controls was 13.9 (95 % CI 9.9-19.7). We found no subjects with homozygous PTM. Double heterozygosity for FVL and PTM was seen in 12 subjects. There was no difference in age at inclusion VTE between double heterozygotes and controls (59 ± 16 vs. 63 ± 17, ns.). DVT was seen in 92 % at inclusion, 8 % had PE. Mean age at first VTE was 52 ± 17 (27-82). Consecutive homozygous FVL patients had a higher age at first thrombosis than previously described. Homozygous females are affected at an earlier age than homozygous men and female controls. It seems that thrombi in homozygous FVL have a different pattern compared to controls i.e. more prone for thrombosis in the lower extremity. The odds ratio for thrombosis among homozygous FVL seems to be lower than previously described.

Location of Retroperitoneal Lymph Node Metastases in Upper Tract Urothelial Carcinoma: Results from a Prospective Lymph Node Mapping Study.

Background: There is limited information on the distribution of retroperitoneal lymph node metastases (LNMs) in upper tract urothelial carcinoma (UTUC). Objective: To investigate the location of LNMs in UTUC of the renal pelvis or proximal ureter and short-term complications after radical nephroureterectomy (RNU) with lymph node dissection (LND). Design setting and participants: This was a prospective Nordic multicenter study (four university hospitals, two county hospitals). Patients with clinically suspected locally advanced UTUC (stage >T1) and/or clinical lymph node-positive (cN+) disease were invited to participate. Participants underwent RNU and fractionated retroperitoneal LND using predefined side-specific templates. Outcome measurements and statistical analysis: The location of LNMs in the LND specimen and retroperitoneal lymph node recurrences during follow-up was recorded. Postoperative complications within 90 d of surgery were ascertained from patient charts. Descriptive statistics were used. Results and limitations: LNMs were present in the LND specimen in 23/100 patients, and nine of 100 patients experienced a retroperitoneal recurrence. Distribution per side revealed LNMs in the LND specimen in 11/38 (29%) patients with right-sided tumors, for whom the anatomically larger, right-sided template was used, in comparison to 12/62 (19%) patients with left-sided tumors, for whom a more limited template was used. High-grade complications (Clavien grade ≥3) within 90 d of surgery were registered for 13/100 patients. The study is limited in size and not powered to assess survival estimates. Conclusions: The suggested templates that we prospectively applied for right-sided and left-sided LND in patients with advanced UTUC included the majority of LNMs. High-grade complications directly related to the LND part of the surgery were limited. Patient summary: This study describes the location of lymph node metastases in patients with cancer in the upper urinary tract who underwent surgery to remove the affected kidney and ureter. The results show that most metastases occur within the template maps for lymph node surgery that we investigated, and that this surgery can be performed with few severe complications.

Abnormal uterine artery Doppler in pregnancies suspected of a SGA fetus is related to increased risk of recurrence during next pregnancy.

OBJECTIVE: To investigate if placental Doppler velocimetry can predict the recurrence of a small-for-gestational age (SGA) fetus in subsequent pregnancies. DESIGN: Retrospective study. SETTING: City cohort over 15 years attending a university hospital. METHODS: A total of 196 pregnancies suspected of a SGA fetus (<3rd percentile) evaluated by uterine and umbilical artery Doppler velocimetry. Blood velocity waveform was analyzed for pulsatility index (PI) as well as the uterine artery waveform for notching in early diastole. MAIN OUTCOME MEASURE: The occurrence of a SGA newborn during the succeeding pregnancy by Doppler results from the previous pregnancy. RESULTS: In the group of 196 pregnancies suspected for SGA, 27 (13.8%) delivered a SGA newborn in the following pregnancy. Thirty-seven (18.9%) of the 196 had an abnormally high PI in the uterine arteries in their first pregnancy, 12 (32.4%) of these delivered a SGA child in the next pregnancy (relative risk 3.44, p<0.001). The corresponding figure for those with normal uterine artery PI was 15 (9.4%). Abnormal umbilical artery Doppler was a worse predictor of recurrence of SGA (p=0.051). Uterine artery notching was not related to a SGA newborn during next pregnancy. CONCLUSION: The results suggest that abnormal uterine artery Doppler is related to increased risk of recurrence of SGA during the next pregnancy. This knowledge might provide the clinician with an opportunity to initiate preventive treatment and increase surveillance to women at risk during succeeding pregnancy.

Evaluation of recurrent venous thromboembolism in patients with Factor V Leiden mutation in heterozygous form.

INTRODUCTION: To evaluate the risk for recurrence after first venous thromboembolism (VTE) among patients with or without Factor V Leiden (FVL) mutation. MATERIALS AND METHODS: A prospective population based study of 1465 consecutive unselected VTE patients was performed at Skåne University Hospital 1998-2008. The VTE was objectively verified and the patients answered questionnaire and left blood samples for evaluation. RESULTS: Out of 1465 patients (721[49%] men and 744[51%] women) thrombophilia data were available for 1267, and FVL mutation was found in heterozygous form in 339 (27). The homozygous form and prothrombin mutation (PTM) were much less common. Patients were followed during 4.8 ± 2.3 years (total 6133 patient years) and recurrence after first VTE (evaluated in 1108 patients) occurred in 131 (12%, 95%CI 10-14%), where of 49(37%) had heterozygous FVL mutation and 57(44%) were without thrombophilia. The remaining 25(19%) patients had either PTM, FVL in homozygous form, compound PTM/FVL or unknown thrombophilia status. Having FVL mutation in heterozygous form significantly increased the risk for VTE recurrence (odds ratio 2.4 (95 %CI 1.6-3.6; p<0.01). In a Kaplan-Meier analysis the FVL group also differed significantly (p<0.01) from the other patients concerning time to recurrence (almost 25% vs. 10% after 8 years). CONCLUSIONS: FVL mutation in heterozygous form is common among VTE patients and significantly increases the risk for VTE recurrence.