Lake sediments as archives of recurrence rates and intensities of past flood events

Palaeoflood hydrology is an expanding field as the damage potential of flood and flood-related processes are increasing with the population density and the value of the infrastructure. Assessing the risk of these hazards in mountainous terrain requires knowledge about the frequency and severness of such events in the past. A wide range of methods is employed using diverse biologic, geomorphic or geologic evidences to track past flood events. Impact of floods are studied and dated on alluvial fans and cones using for example the growth disturbance of trees (Stoffel and Bollschweiler 2008; Schneuwly-Bollschweiler and Stoffel 2012: this volume) or stratigraphic layers deposited by debris flows, allowing to reconstruct past flood frequencies (Bardou et~al. 2003). Further downstream, the classical approach of palaeoflood hydrology (Kochel and Baker 1982) utilizes geomorphic indicators such as overbank sediments, silt lines and erosion features of floods along a river (e.g. Benito and Thorndycraft 2005). Fine-grained sediment settles out of the river suspension in eddies or backwater areas, where the flow velocity of the river is reduced. Records of these deposits at different elevations across a river’s profile can be used to assess the discharge of the past floods. This approach of palaeoflood hydrology studies was successfully applied in several river catchments (e.g. Ely et al. 1993; Macklin and Lewin 2003; O’Connor et al. 1994; Sheffer et al. 2003; Thorndycraft et al. 2005; Thorndycraft and Benito 2006). All these different reconstruction methods have their own advantages and disadvantages, but often these studies have a limited time coverage and the records are potentially incomplete due to lateral limits of depositional areas and due to the erosional power of fluvial processes that remove previously deposited flood witnesses. Here, we present a method that follows the sediment particle transported by a flood event to its final sink: the lacustrine basin.

Disease progression and recurrence in women treated for vulvovaginal intraepithelial neoplasia

OBJECTIVE The malignant potential of intraepithelial neoplasia of the vulva and vagina after treatment is not well defined. Our objective was to examine risk factors for recurrence and invasive disease. METHODS Four hundred sixty-four women with biopsy proven high-grade intraepithelial neoplasia of the vulva and vagina were identified in the electronic databases of four colposcopy clinics. Inclusion criteria were a follow-up of more than one year, no history of invasive cancer and no invasive cancer within the first year after initial treatment. We investigated the potential factors associated with recurrence and progression using a logistic regression analysis to estimate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS Of the 411 eligible patients, 123 patients (29.9%) recurred later than one year after initial treatment and 24 patients (5.8%) progressed to invasive disease. According to multivariate analyses, the risk factors associated with recurrence were multifocality (OR, 3.33; 95% CI, 2.02 to 5.51), immunosuppression (OR, 2.51; 95% CI, 1.09 to 5.81), excision as initial treatment (vs. laser evaporation; OR, 1.79; 95% CI, 1.11 to 2.91) and smoking (OR, 1.61; 95% CI, 1.02 to 2.55). Risk factors for progression to invasive disease were immunosuppression (OR, 4.00; 95% CI, 1.30 to 12.25), multifocality (OR, 3.05; 95% CI, 1.25 to 7.43) and smoking (OR, 2.97; 95% CI, 1.16 to 7.60), but not treatment modality. CONCLUSION Laser evaporation combined with extensive biopsy is at least as efficacious as initial treatment of intraepithelial neoplasia with excision. Smoking is a risk factor for both recurrence and progression to invasive disease. Hence, smoking cessation should be advised and maintaining a long follow-up period due to late relapses is necessary.

Influence of intervertebral disc fenestration at the herniation site in association with hemilaminectomy on recurrence in chondrodystrophic dogs with thoracolumbar disc disease: a prospective MRI study

OBJECTIVE To describe the influence of fenestration at the disc herniation site on recurrence in thoracolumbar disc disease of chondrodystrophoid dogs. STUDY DESIGN Prospective clinical study. ANIMALS Chondrodystrophic dogs (n=19). METHODS Dogs were divided into 2 groups: group 1 (9 dogs) had thoracolumbar disc extrusion (Hansen type I) treated by hemilaminectomy and concomitant fenestration of the affected intervertebral disc and group 2 (10 dogs) had hemilaminectomy without fenestration. All dogs had 3 magnetic resonance imaging (MRI) examinations: preoperatively, immediately postoperatively to assess removal of herniated disc material, and again 6 weeks after surgery. RESULTS There were 13 male and 6 female dogs; mean age, 7.1 years. Thoracolumbar disc herniation was confirmed with MRI. Immediate post surgical MRI revealed that the herniated disc removal was complete in all but 1 dog and that fenestration did not lead to complete removal of nucleus pulposus within the intervertebral disc space. On the 3rd MRI examination, none of the group 1 dogs had further disc material herniation at the fenestrated site. Six of the 10 group 2 dogs had a recurrence of herniation leading to clinical signs in 3 dogs (pain in 2 dogs, paresis in 1 dog). CONCLUSION In thoracolumbar disc herniation, fenestration of the affected intervertebral disc space prevents further extrusion of disc material. CLINICAL RELEVANCE Fenestration reduces the risk of early recurrence of disc herniation and associated postoperative complications.

Tumour genomic and microenvironmental heterogeneity for integrated prediction of 5-year biochemical recurrence of prostate cancer: a retrospective cohort study.

BACKGROUND Clinical prognostic groupings for localised prostate cancers are imprecise, with 30-50% of patients recurring after image-guided radiotherapy or radical prostatectomy. We aimed to test combined genomic and microenvironmental indices in prostate cancer to improve risk stratification and complement clinical prognostic factors. METHODS We used DNA-based indices alone or in combination with intra-prostatic hypoxia measurements to develop four prognostic indices in 126 low-risk to intermediate-risk patients (Toronto cohort) who will receive image-guided radiotherapy. We validated these indices in two independent cohorts of 154 (Memorial Sloan Kettering Cancer Center cohort [MSKCC] cohort) and 117 (Cambridge cohort) radical prostatectomy specimens from low-risk to high-risk patients. We applied unsupervised and supervised machine learning techniques to the copy-number profiles of 126 pre-image-guided radiotherapy diagnostic biopsies to develop prognostic signatures. Our primary endpoint was the development of a set of prognostic measures capable of stratifying patients for risk of biochemical relapse 5 years after primary treatment. FINDINGS Biochemical relapse was associated with indices of tumour hypoxia, genomic instability, and genomic subtypes based on multivariate analyses. We identified four genomic subtypes for prostate cancer, which had different 5-year biochemical relapse-free survival. Genomic instability is prognostic for relapse in both image-guided radiotherapy (multivariate analysis hazard ratio [HR] 4·5 [95% CI 2·1-9·8]; p=0·00013; area under the receiver operator curve [AUC] 0·70 [95% CI 0·65-0·76]) and radical prostatectomy (4·0 [1·6-9·7]; p=0·0024; AUC 0·57 [0·52-0·61]) patients with prostate cancer, and its effect is magnified by intratumoral hypoxia (3·8 [1·2-12]; p=0·019; AUC 0·67 [0·61-0·73]). A novel 100-loci DNA signature accurately classified treatment outcome in the MSKCC low-risk to intermediate-risk cohort (multivariate analysis HR 6·1 [95% CI 2·0-19]; p=0·0015; AUC 0·74 [95% CI 0·65-0·83]). In the independent MSKCC and Cambridge cohorts, this signature identified low-risk to high-risk patients who were most likely to fail treatment within 18 months (combined cohorts multivariate analysis HR 2·9 [95% CI 1·4-6·0]; p=0·0039; AUC 0·68 [95% CI 0·63-0·73]), and was better at predicting biochemical relapse than 23 previously published RNA signatures. INTERPRETATION This is the first study of cancer outcome to integrate DNA-based and microenvironment-based failure indices to predict patient outcome. Patients exhibiting these aggressive features after biopsy should be entered into treatment intensification trials. FUNDING Movember Foundation, Prostate Cancer Canada, Ontario Institute for Cancer Research, Canadian Institute for Health Research, NIHR Cambridge Biomedical Research Centre, The University of Cambridge, Cancer Research UK, Cambridge Cancer Charity, Prostate Cancer UK, Hutchison Whampoa Limited, Terry Fox Research Institute, Princess Margaret Cancer Centre Foundation, PMH-Radiation Medicine Program Academic Enrichment Fund, Motorcycle Ride for Dad (Durham), Canadian Cancer Society.

Treatment and outcomes of urethral recurrence of urinary bladder cancer in women after radical cystectomy and orthotopic neobladder: a series of 12 cases

INTRODUCTION The incidence, treatment, and outcome of urethral recurrence (UR) after radical cystectomy (RC) for muscle-invasive bladder cancer with orthotopic neobladder in women have rarely been addressed in the literature. PATIENTS AND METHODS A total of 12 patients (median age at recurrence: 60 years) who experienced UR after RC with an orthotopic neobladder were selected for this study from a cohort of 456 women from participating institutions. The primary clinical and pathological characteristics at RC, including the manifestation of the UR and its treatment and outcome, were reviewed. RESULTS The primary bladder tumors in the 12 patients were urothelial carcinoma in 8 patients, squamous cell carcinoma and adenocarcinoma in 1 patient each, and mixed histology in 2 patients. Three patients (25%) had lymph node-positive disease at RC. The median time from RC to the detection of UR was 8 months (range 4-55). Eight recurrences manifested with clinical symptoms and 4 were detected during follow-up or during a diagnostic work-up for clinical symptoms caused by distant metastases. Treatment modalities were surgery, chemotherapy, radiotherapy, and bacillus Calmette-Guérin urethral instillations. Nine patients died of cancer. The median survival after the diagnosis of UR was 6 months. CONCLUSIONS UR after RC with an orthotopic neobladder in females is rare. Solitary, noninvasive recurrences have a favorable prognosis when detected early. Invasive recurrences are often associated with local and distant metastases and have a poor prognosis. © 2014 S. Karger AG, Basel.

Methylation of PITX2, HOXD3, RASSF1 and TDRD1 predicts biochemical recurrence in high-risk prostate cancer

PURPOSE To explore differential methylation of HAAO, HOXD3, LGALS3, PITX2, RASSF1 and TDRD1 as a molecular tool to predict biochemical recurrence (BCR) in patients with high-risk prostate cancer (PCa). METHODS A multiplexed nested methylation-specific PCR was applied to quantify promoter methylation of the selected markers in five cell lines, 42 benign prostatic hyperplasia (BPH) and 71 high-risk PCa tumor samples. Uni- and multivariate Cox regression models were used to assess the importance of the methylation level in predicting BCR. RESULTS A PCa-specific methylation marker HAAO in combination with HOXD3 and a hypomethylation marker TDRD1 distinguished PCa samples (>90 % of tumor cells each) from BPH with a sensitivity of 0.99 and a specificity of 0.95. High methylation of PITX2, HOXD3 and RASSF1, as well as low methylation of TDRD1, appeared to be significantly associated with a higher risk for BCR (HR 3.96, 3.44, 2.80 and 2.85, correspondingly) after correcting for established risk factors. When DNA methylation was treated as a continuous variable, a two-gene model PITX2 × 0.020677 + HOXD3 × 0.0043132 proved to be the best predictor of BCR (HR 4.85) compared with the individual markers. This finding was confirmed in an independent set of 52 high-risk PCa tumor samples (HR 11.89). CONCLUSIONS Differential promoter methylation of HOXD3, PITX2, RASSF1 and TDRD1 emerges as an independent predictor of BCR in high-risk PCa patients. A two-gene continuous DNA methylation model "PITX2 × 0.020677 + HOXD3 × 0.0043132" is a better predictor of BCR compared with individual markers.

Low back pain risk factors associated with persistence, recurrence and delayed presentation

BACKGROUND: There is little knowledge in the literature on the role of time-related variables for the prognosis of acute and subacute low back pain (LBP). OBJECTIVE: The aim of this study was to estimate the relationship between time-related LBP characteristics and prognostic factors for acute/subacute LBP. METHODS: We performed a prospective inception cohort study of 315 patients attending a health practitioner for acute/subacute LBP or recurrent LBP. One-tailed correlations were conducted between patient characteristics and time-related variables. RESULTS: The pattern of correlation between risk factors for and resources against persistent LBP differed between three time-related variables. 'Subacute LBP' and 'delayed presentation' were positively associated with psychological factors. Both indicators were negatively correlated with resources against development of persistent LBP. Moreover, 'delayed presentation' was related positively with occupational stressors. In contrast, 'recurrent LBP' was only related to more impaired health-related factors. CONCLUSIONS: Patients with current LBP waiting longer until seeking help in primary care have a more disadvantageous profile of occupational and psychological risk factors and lower resource levels. A similar but less pronounced pattern occurred in those with subacute LBP compared to those with acute LBP. Consideration of time characteristics of LBP may help to better understand LBP.

Laparoscopic management of bowel endometriosis: resection margins as a predictor of recurrence.

OBJECTIVE To evaluate possible predictive factors for recurrence after laparoscopic segmental bowel resection for bowel endometriosis. DESIGN Cohort study. SETTING Academic tertiary referral center. METHODS 95 symptomatic women with bowel endometriosis who underwent laparoscopic segmental bowel resection at the Endometriosis clinic, University of Berne, between 2002 and 2012 were enrolled. Since 14 women were lost to follow-up, 81 formed the final cohort. Clinical and histological characteristics were examined as possible predictive factors for disease recurrence. MAIN OUTCOME MEASURES Recurrence, defined as a subsequent operation due to recurrent endometriosis-associated pain with a histologically confirmed endometriotic lesion. RESULTS Recurrence was observed in 13 (16%) patients. Variables that were significantly associated to recurrence by the Cox regression analysis were positive bowel resection margins (hazard ratio 6.5, 95% confidence interval 1.8-23.5, p = 0.005), age <31 years (hazard ratio 5.6, 95% confidence interval 1.7-18.6, p = 0.005) and body mass index ≥23 kg/m(2) (hazard ratio 11.0, 95% confidence interval 2.7-44.6, p = 0.001). CONCLUSIONS Positive bowel resection margins as well as age <31 years and body mass index ≥23 kg/m(2) appear to be independent predictors of disease recurrence.

Urethral recurrence in women with orthotopic bladder substitutes: A multi-institutional study.

OBJECTIVES To evaluate risk factors for urethral recurrence (UR) in women with neobladder. MATERIAL AND METHODS From 1994 to 2011, 297 women (median age = 54y; interquartile range: 47-57) underwent radical cystectomy with ileal neobladder for bladder cancer in 4 centers. None of the patients had bladder neck involvement at preoperative assessment. Univariable and multivariable analyses were used to estimate recurrence-free survival and overall survival. The median follow-up was 64 months (interquartile range: 25-116). RESULTS Of the 297 patients, 81 developed recurrence (27%). The 10- and 15-year recurrence-free survival rates were 66% and 66%, respectively. The 10- and 15-year overall survival rates were 57% and 55%, respectively. UR occurred in 2 patients (0.6%) with solitary urethral, 4 (1.2%) with concomitant urethral and distant recurrence, and 1 with concomitant urethral and local recurrence (0.3%). Bladder tumors were located at the trigone in 27 patients (9.1%). None of these patients developed UR. Lymph node tumor involvement was present in 60 patients (20.2%). On univariable and multivariable analyses, pathologic tumor and nodal stage were independent predictors for the overall risk of recurrence. UR was associated with a positive final urethral margin status (P<0.001) whereas no significant associations were found for carcinoma in situ, pathologic tumor and nodal stage, and bladder trigone involvement. CONCLUSIONS In this series, only 0.6% of women developed solitary UR. A positive final urethral margin was associated with an increased risk of UR. Women with involvement of the bladder trigone were not at higher risk of UR.

Thrombophilia and risk of VTE recurrence according to the age at the time of first VTE manifestation

BACKGROUND Whether screening for thrombophilia is useful for patients after a first episode of venous thromboembolism (VTE) is a controversial issue. However, the impact of thrombophilia on the risk of recurrence may vary depending on the patient's age at the time of the first VTE. PATIENTS AND METHODS Of 1221 VTE patients (42 % males) registered in the MAISTHRO (MAin-ISar-THROmbosis) registry, 261 experienced VTE recurrence during a 5-year follow-up after the discontinuation of anticoagulant therapy. RESULTS Thrombophilia was more common among patients with VTE recurrence than those without (58.6 % vs. 50.3 %; p = 0.017). Stratifying patients by the age at the time of their initial VTE, Cox proportional hazards analyses adjusted for age, sex and the presence or absence of established risk factors revealed a heterozygous prothrombin (PT) G20210A mutation (hazard ratio (HR) 2.65; 95 %-confidence interval (CI) 1.71 - 4.12; p < 0.001), homozygosity/double heterozygosity for the factor V Leiden and/or PT mutation (HR 2.35; 95 %-CI 1.09 - 5.07, p = 0.030), and an antithrombin deficiency (HR 2.12; 95 %-CI 1.12 - 4.10; p = 0.021) to predict recurrent VTE in patients aged 40 years or older, whereas lupus anticoagulants (HR 3.05; 95%-CI 1.40 - 6.66; p = 0.005) increased the risk of recurrence in younger patients. Subgroup analyses revealed an increased risk of recurrence for a heterozygous factor V Leiden mutation only in young females without hormonal treatment whereas the predictive value of a heterozygous PT mutation was restricted to males over the age of 40 years. CONCLUSIONS Our data do not support a preference of younger patients for thrombophilia testing after a first venous thromboembolic event.

Recurrence-free survival, but not surgical therapy per se, determines 583 patients' long-term satisfaction following primary pilonidal sinus surgery.

PURPOSE With pilonidal sinus disease (PSD) incidence increasing and patients freely choosing their surgeon, patients' interest issues have been brought forward estimating patient satisfaction following pilonidal sinus surgery. The influence of wound healing time and long-term recurrence rate on patient satisfaction in primary PSD surgery has not been investigated yet. METHODS Five hundred eighty-three patients (German military cohort) were interviewed, compiling wound healing time, aesthetic satisfaction, long-term recurrence-free survival and patient satisfaction having undergone primary open (PO) treatment, marsupialization (MARS) or primary midline closure (PMC) treatment. Recurrence rate was determined by Kaplan-Meier calculation following up to 20 years after primary PSD surgery. RESULTS Patient satisfaction ranking from 1 to 10 (10 = max. satisfied) showed an average satisfaction of 8.2 (range 0-10; 95% confidence interval (CI) 7891-8250). In-hospital stay time was significantly longer in primary open (PO) and marsupialization (MARS) group as compared to primary midline closure (PMC; p < 0.0001, Kruskal-Wallis test). Satisfaction was comparable between treatment groups, and was neither linked to in-hospital stay time nor to longer outpatient wound care period or total treatment time. Recurrence-free survival, as seen in the PO and PMC treatment group, revealed a highly significant difference for all patients. Improvement in MARS patients with versus without recurrence was low, as satisfaction with primary treatment was lower as the other groups. CONCLUSIONS Neither choice of surgical treatment nor treatment duration within hospital or after hospital influences patient satisfaction, as long as recurrence-free survival can be provided. Marsupialization was ranked lower in both groups (with or without recurrence), and should be abandoned, as patients are significantly less satisfied with either results, independent of recurrence.

Does Full Wound Rupture following Median Pilonidal Closure Alter Long-Term Recurrence Rate?

OBJECTIVE The purpose of this study was to examine the recurrence rate of wound rupture in primary pilonidal sinus disease (PSD) after median closure. SUBJECTS AND METHODS A total of 583 patients from the German military cohort were interviewed. We compared the choice of surgical therapy, wound dehiscence (if present) and long-term recurrence-free survival for patients with primary open treatment, marsupialization and primary median treatment (closed vs. secondary open, respectively). Actuarial recurrence rate was determined using the Kaplan-Meier calculation with a follow-up of up to 20 years after primary PSD surgery. RESULTS Patients with excision followed by primary open wound treatment showed a significantly lower 5- than 10-year recurrence rate (8.3 vs. 11.2%) compared to the patients with primary midline closure (17.4 vs. 20.5%, p = 0.03). The 20-year recurrence rate was 28% in primary open wound treatment versus 44% in primary midline closure without wound rupture. In contrast to these findings, long-term recurrence rates following secondary open wound treatment (12.2% at 5 years vs. 17.1% at 10 years) tended to be higher (although not significantly, p = 0.57) compared to primary open treatment (8.3% at 5 years vs. 11.2% at 10 years). There was no statistical difference in long-term recurrence rates between secondary open and primary midline closure (p = 0.7). Hence, despite only a short wound closure time experienced before wound rupture, the patient does not fully benefit from an open wound treatment in terms of recurrence rate. CONCLUSION The postoperative pilonidal sinus wound rupture of primary midline closures did not significantly increase the 5- and 10-year long-term recurrence rates compared to uneventfully healing primary midline closures.

Predicting recurrence after unprovoked venous thromboembolism: prospective validation of the updated Vienna Prediction Model.

The updated Vienna Prediction Model for estimating recurrence risk after an unprovoked venous thromboembolism (VTE) has been developed to identify individuals at low risk for VTE recurrence in whom anticoagulation (AC) therapy may be stopped after 3 months. We externally validated the accuracy of the model to predict recurrent VTE in a prospective multicenter cohort of 156 patients aged ≥65 years with acute symptomatic unprovoked VTE who had received 3 to 12 months of AC. Patients with a predicted 12-month risk within the lowest quartile based on the updated Vienna Prediction Model were classified as low risk. The risk of recurrent VTE did not differ between low- vs higher-risk patients at 12 months (13% vs 10%; P = .77) and 24 months (15% vs 17%; P = 1.0). The area under the receiver operating characteristic curve for predicting VTE recurrence was 0.39 (95% confidence interval [CI], 0.25-0.52) at 12 months and 0.43 (95% CI, 0.31-0.54) at 24 months. In conclusion, in elderly patients with unprovoked VTE who have stopped AC, the updated Vienna Prediction Model does not discriminate between patients who develop recurrent VTE and those who do not. This study was registered at www.clinicaltrials.gov as #NCT00973596.

Rapid Recurrence of a Benign Meningial Perineurioma.

BACKGROUND We describe a rare case of a rapidly recurring benign meningial-based perineurioma. Clinical, radiologic, and pathologic features of a rapidly recurring falxial perineurioma are described; the perineurioma was discovered incidentally in an 86-year-old woman. CASE DESCRIPTION Due to progressive gait disturbances and radiologically proven progression after a 3-year symptom-free interval, subtotal resection of a large falxial-based meningeal tumor was performed. CONCLUSIONS The pathologic examination confirmed the diagnosis of a perineurioma (World Health Organization grade I). Follow-up magnetic resonance tomography 5 months later due to neurologic deterioration revealed an abnormally rapidly growing and extensive local tumor recurrence. Due to the mass effect, reoperation was performed and adjuvant radiation of 20 Gy to the tumor bed was implemented thereafter. Meningeal-based perineuriomas of the central nervous system are extremely rare, and literature on proper management is scarce. Although histologic classification reveals a benign lesion, follow-up may be considered for this type of tumor.