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Background: The impact of intraoperative fluid management during cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) on postoperative outcomes has been poorly investigated. This study aimed to retrospectively evaluate the impact of intraoperative fluid management strategy on postoperative outcomes and survival., Methods: 509 patients undergoing CRS and HIPEC at Uppsala University Hospital/Sweden 2004-2017 were categorized into two groups according to the intraoperative fluid management strategy: pre-goal directed therapy (pre-GDT) and goal directed therapy (GDT), where a hemodynamic monitor (CardioQ or FloTrac/Vigileo) was used to optimize fluid management. Impact on morbidity, postoperative hemorrhage, length-of-stay and survival was analyzed., Results: The pre-GDT group received higher fluid volume compared to the GDT group (mean 19.9 vs. 16.2 ml/kg/h, p < 0.001). Overall postoperative morbidity Grade III-V was higher in the GDT group (30% vs. 22%, p = 0.03). Multivariable adjusted odds ratio (OR) for Grade III-V morbidity was 1.80 (95%CI 1.10-3.10, p = 0.02) in the GDT group. Numerically, more cases of postoperative hemorrhage were found in the GDT group (9% vs. 5%, p = 0.09), but no correlation was observed in the multivariable analysis 1.37 (95%CI 0.64-2.95, p = 0.40). An oxaliplatin regimen was a significant risk factor for postoperative hemorrhage (p = 0.03). Mean length of stay was shorter in the GDT group (17 vs. 26 days, p < 0.0001). Survival did not differ between the groups., Conclusion: While GDT increased the risk for postoperative morbidity, it was associated with shortened hospital stay. Intraoperative fluid management during CRS and HIPEC did not affect the postoperative risk for hemorrhage, while the use of an oxaliplatin regimen did., Competing Interests: Declaration of competing interest There is no conflict of interest in this study or in the article submitted. None of the authors has personal or financial interests in, or has received financial support from, any industrial source., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Combining hyperthermic intraperitoneal chemotherapy (HIPEC) treatment with early postoperative intraperitoneal chemotherapy (EPIC) may increase postoperative morbidity. This study aims to investigate postoperative morbidity after HIPEC+EPIC compared with HIPEC alone in patients with peritoneal metastases (PM)., Materials and Methods: This is a retrospective propensity score matched cohort study. All patients undergoing PM treatment at Uppsala University Hospital between February 2004 and December 2014 were included. Propensity score matching with a 1:1 ratio was performed using sex, primary tumor site, preoperative chemotherapy, peritoneal cancer index, completeness of cytoreduction score, and HIPEC regimen. Length of hospital stay, morbidity, reoperation rate, and readmission rate within 6 months were selected as endpoints., Results: A total of 390 consecutive patients were divided in two arms: HIPEC+EPIC (n = 115) and HIPEC alone (n = 275). The propensity score matching (n = 190) was successful with balanced covariates: 95 patients/arm. The length of stay (LOS) was longer in the HIPEC + EPIC group in the total cohort (30 vs 24 days, p < 0.001), with a trend towards significance in the propensity matched group (29 vs 25 days, p = 0.062). No other differences in endpoints were found., Conclusion: HIPEC+EPIC is associated with a prolonged hospital stay, but with no statistically significant relevant increase in postoperative morbidity, reoperation rate or incidence of readmission., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier Ltd.)

Background: Oophorectomy is a common procedure in women with peritoneal metastasis (PM) undergoing cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC), which has unique consequences on hormonal balance and fertility before menopause. The objective of this study was to analyze histopathological results and the prognostic influence of ovarian involvement., Material and Methods: A prospective HIPEC database was used to identify 442 patients with PM from colorectal cancer, pseudomyxoma peritonei and appendix cancer scheduled for CRS-HIPEC between 2012 and 2019 at the University Hospital, Uppsala, Sweden. Statistical analyses were performed using the Chi-square test and Cox regression analysis., Results: In all, 103 of 180 females underwent oophorectomy. Unilateral oophorectomy was performed in 19% (n = 20) and bilateral oophorectomy in 81% (n = 83). The median age was 61 (range 20-80). Benign ovarian histopathology was seen in 23% (n = 24). Of these, two patients were ≤35 years and 8 patients ≤50 years. The median peritoneal cancer index (PCI) was 16 in women undergoing oophorectomy, and 7 in those with no oophorectomy. Bilateral oophorectomy was associated with negative impact on overall survival (HR 4.84; 95% CI; 1.14-20.61). Malignant ovarian histopathology was also associated with a negative impact on overall survival (p = 0.043)., Conclusion: Almost a quarter of the patients had benign histopathology after oophorectomy. This is crucial information for females with childbearing potential when planning for extensive surgery. Extensive pelvic peritoneal cancer growth resulted more often in bilateral oophorectomy which influenced survival negatively., (Copyright © 2021 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

River systems have undergone a massive transformation since the Anthropocene. The natural properties of river systems have been drastically altered and reshaped, limiting the use of management frameworks, their scientific knowledge base and their ability to provide adequate solutions for current problems and those of the future, such as climate change, biodiversity crisis and increased demands for water resources. To address these challenges, a socioecologically driven research agenda for river systems that complements current approaches is needed and proposed. The implementation of the concepts of social metabolism and the colonisation of natural systems into existing concepts can provide a new basis to analyse the coevolutionary coupling of social systems with ecological and hydrological (i.e., 'socio-ecohydrological') systems within rivers. To operationalize this research agenda, we highlight four initial core topics defined as research clusters (RCs) to address specific system properties in an integrative manner. The colonisation of natural systems by social systems is seen as a significant driver of the transformation processes in river systems. These transformation processes are influenced by connectivity (RC 1), which primarily addresses biophysical aspects and governance (RC 2), which focuses on the changes in social systems. The metabolism (RC 3) and vulnerability (RC 4) of the social and natural systems are significant aspects of the coupling of social systems and ecohydrological systems with investments, energy, resources, services and associated risks and impacts. This socio-ecohydrological research agenda complements other recent approaches, such as 'socio-ecological', 'socio-hydrological' or 'socio-geomorphological' systems, by focusing on the coupling of social systems with natural systems in rivers and thus, by viewing the socioeconomic features of river systems as being just as important as their natural characteristics. The proposed research agenda builds on interdisciplinarity and transdisciplinarity and requires the implementation of such programmes into the education of a new generation of river system scientists, managers and engineers who are aware of the transformation processes and the coupling between systems., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Introduction: prediction and importance of severe postoperative complications after ovarian cancer surgery is a strong issue in patient selection and evaluation. Pre- and early peroperative predictors of severe 30-days postoperative complications (Clavien-Dindo class ≥3) after surgery for primary ovarian cancer are not fully established, neither their impact on patients' survival., Materials and Methods: A prospective observational study included 256 patients with primary ovarian cancer FIGO stages IIB-IV, operated during 2009-2018 in a primary or interval debulking surgery setting. Patient variables were analysed in relation to severe postoperative complications (Clavien-Dindo class ≥3) and overall survival., Results: High-grade postoperative complications occurred in 24.2% patients. Class 3a complications were observed in 12.5% cases. High-grade complications class ≥3 were observed in 31.6% after primary debulking surgery compared to 12.2% after interval debulking surgery (p = 0.0004). Peritoneal cancer index ≥21 and preoperative albumin concentration ≤33 g/L were independent predictors of high-grade complications. Peritoneal cancer index correlated with the surgical complexity score and completeness of cytoreduction. Increased peritoneal cancer index was a negative predictor of overall survival, but high-grade complications did not influence survival negatively., Conclusions: Peritoneal cancer index ≥21 was an independent predictor of high-grade complications after ovarian cancer surgery. Increased peritoneal cancer index also impacted overall survival negatively, but high-grade complications did not influence overall survival., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interests., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Two factors complicate the ecological status classification of very large rivers in Europe according to the EU Water Framework Directive: First, current assessment methods do not fully consider the specific ecology of very large rivers (such as lateral connectivity and the role of floodplains for ecological status). Second, most of Europe's very large rivers have been severely altered by human activities such as flood protection, damming and navigation. The aim of our study is to develop an assessment method for very large rivers by identifying suitable biological metrics as the basis for multi-metric bioassessment using benthic invertebrates. Based on the pan-European typology of very large rivers by Borgwardt et al. (2019), we established a river type-specific assessment approach using invertebrate samples from 25 European countries and 94 very large rivers. The frequency and intensity of eight pressures jointly acting on the sampling sites were described, and a selection of suitable invertebrate community metrics were correlated with the pressure intensities to establish pressure-response relationships. The very large river types differ in terms of relevant pressures and pressure combinations, with the invertebrate communities distinctly responding to these pressure patterns. Neozoa dominance correlated strongly with 'navigation', being a major pressure at very large rivers, which entails severe hydro-morphological alterations such as channelization, riparian vegetation alteration and impoundment. Under combined pressures, a critical community turnover became evident in terms of neozoa outnumbering EPT taxa and the ratio of hemilimnic invertebrates decreasing. We propose ten bioassessment metrics, including measures of biological diversity as well as newly generated indicators, for the development of a European type-specific assessment method for very large rivers., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Peritoneal cancer index (PCI) >20 is often seen as a contraindication for cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with peritoneal metastases (PM) from colorectal cancer. The aim of this study was to compare the overall survival in colorectal PM patients with PCI >20 and PCI ≤20 treated with CRS and HIPEC to those having open-close/debulking procedure only., Methods: All patients with colorectal PM and intention to treat with CRS and HIPEC in Uppsala Sweden 2004-2017 were included. Patients scheduled for CRS and HIPEC were divided into three groups, PCI >20, PCI ≤20, and those not operated with CRS and HIPEC stated as open-close including those treated with palliative debulking., Results: Of 201 operations, 112 (56%) resulted in CRS and HIPEC with PCI ≤20, 45 (22%) in CRS and HIPEC with PCI >20 and 44 (22%) resulted in open-close/debulking. Median survival for CRS and HIPEC and PCI >20 was 20 months (95%CI 14-27 months) with 7% surviving longer than 5 years (n = 3). For CRS and HIPEC and PCI ≤20 the median survival was 33 months (95%CI 30-39 months) with 23% (n = 26) surviving >5years. The median survival for open-close was 9 months (95%CI 4-10 months), no one survived >5years., Conclusion: Patients with PM from colorectal cancer and PCI >20 that were treated with CRS and HIPEC experience a one year longer and doubled overall survival compared with open-close/debulking patients. In addition to PCI, more factors should be taken into account when a decision about proceeding with CRS or not is taken., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Hydropower generation has advantages for societies that seek low-carbon, renewable energy alternatives, but sustainable hydropower production will require an explicit consideration of potential tradeoffs between socioeconomic and environmental priorities. These tradeoffs are often explored during a formal environmental impact assessment process that can be complex and controversial. The steps taken to address stakeholder concerns through impact hypotheses and field studies are not always transparent. We have created a Checklist of River Function Indicators to facilitate stakeholder discussions during hydropower licensing and to support more transparent, holistic, and scientifically informed hydropower environmental analyses. Based on a database of environmental metrics collected from hydropower project studies documented by the Federal Energy Regulatory Commission (FERC), the International Hydropower Association, the Low Impact Hydropower Institute, and peer-reviewed scientific literature, our proposed Checklist of River Function Indicators contains 51 indicators in six categories. We have tested the usefulness of the Indicators by applying them to seven hydropower projects documented by FERC. Among the case study projects, 44 of the 51 Indicators were assessed according to the FERC documentation. Even though each hydropower project presents unique natural resource issues and stakeholder priorities, the proposed Indicators can provide a transparent starting point for stakeholder discussions about which ecological impacts should be considered in hydropower planning and relicensing assessments., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Effective identification of species using short DNA fragments (DNA barcoding and DNA metabarcoding) requires reliable sequence reference libraries of known taxa. Both taxonomically comprehensive coverage and content quality are important for sufficient accuracy. For aquatic ecosystems in Europe, reliable barcode reference libraries are particularly important if molecular identification tools are to be implemented in biomonitoring and reports in the context of the EU Water Framework Directive (WFD) and the Marine Strategy Framework Directive (MSFD). We analysed gaps in the two most important reference databases, Barcode of Life Data Systems (BOLD) and NCBI GenBank, with a focus on the taxa most frequently used in WFD and MSFD. Our analyses show that coverage varies strongly among taxonomic groups, and among geographic regions. In general, groups that were actively targeted in barcode projects (e.g. fish, true bugs, caddisflies and vascular plants) are well represented in the barcode libraries, while others have fewer records (e.g. marine molluscs, ascidians, and freshwater diatoms). We also found that species monitored in several countries often are represented by barcodes in reference libraries, while species monitored in a single country frequently lack sequence records. A large proportion of species (up to 50%) in several taxonomic groups are only represented by private data in BOLD. Our results have implications for the future strategy to fill existing gaps in barcode libraries, especially if DNA metabarcoding is to be used in the monitoring of European aquatic biota under the WFD and MSFD. For example, missing species relevant to monitoring in multiple countries should be prioritized for future collaborative programs. We also discuss why a strategy for quality control and quality assurance of barcode reference libraries is needed and recommend future steps to ensure full utilisation of metabarcoding in aquatic biomonitoring., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

The bioassessment of aquatic ecosystems is currently based on various biotic indices that use the occurrence and/or abundance of selected taxonomic groups to define ecological status. These conventional indices have some limitations, often related to difficulties in morphological identification of bioindicator taxa. Recent development of DNA barcoding and metabarcoding could potentially alleviate some of these limitations, by using DNA sequences instead of morphology to identify organisms and to characterize a given ecosystem. In this paper, we review the structure of conventional biotic indices, and we present the results of pilot metabarcoding studies using environmental DNA to infer biotic indices. We discuss the main advantages and pitfalls of metabarcoding approaches to assess parameters such as richness, abundance, taxonomic composition and species ecological values, to be used for calculation of biotic indices. We present some future developments to fully exploit the potential of metabarcoding data and improve the accuracy and precision of their analysis. We also propose some recommendations for the future integration of DNA metabarcoding to routine biomonitoring programs., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Early diagnosis to target minimal volume disease has received increased attention in the management of appendiceal and colorectal peritoneal metastases (PM). This study aimed to identify risk factors for appendiceal, colon and rectal PM., Methods: Data were retrieved from the Swedish Colorectal Cancer Registry for all patients undergoing bowel resection of appendiceal and colorectal tumours, in Sweden, 2007-2015. Risk factors for synchronous and metachronous PM were analysed with multivariate logistic and Cox proportional hazard regression models., Results: Synchronous PM was most common in appendiceal cancer (23.5%), followed by colon (3.1%) and rectal (0.6%) cancer. The 5-year cumulative incidence was 9.0% for appendiceal, 2.5% for right colon, 1.8% for left colon and 1.2% for rectal cancer. In appendiceal cancer (n = 327), T4, N2, mucinous tumour, and non-radical surgery were associated with PM. In colon cancer (n = 24,399), synchronous PM were primarily associated with T4 (OR 18.37, 95% CI 8.12-41.53), T3 and N2 but also with N1, right-sided tumour, mucinous tumour, vascular and perineural invasion, female gender, age <60 and emergency surgery. These factors were also associated with metachronous PM. In rectal cancer (n = 10,394), T4 (OR 19.12, 95% CI 5.52-66.24), proximal tumour and mucinous tumour were associated with synchronous PM and T4 and mucinous tumour with metachronous PM., Conclusions: This study shows that appendiceal cancer, right-sided colon cancer, advanced tumour and node stages and mucinous histopathology are the main high-risk features for PM and should increase the awareness of current or future PM., (Copyright © 2018 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Large rivers cover and function over large spatial extents. Accordingly, the detailed assessment of their morphology is complex. Here, a methodology is presented to assess large rivers' morphology (LaRiMo) based on free datasets of geographic information systems. This approach could help to achieve a comparable, transboundary assessment of large river morphology to support the implementation of the European Water Framework Directive. The analyses are based on seven parameters describing processes and characteristics related to large river morphology. These parameters are evaluated for and compared between the rivers Danube, Elbe and Loire. A significantly higher amount of gravel and sand bars within the river bed strongly supported the overall higher morphological status of the Loire. A PCA highlighted that the parameters Wetlands, Active Riparian Zones and Free Flowing Sections similarly described a good morphological situation. In contrast, Canal, Dams and Impervious Surface indicated bad morphological conditions. Finally, the approach was successfully validated with data from a detailed, field-based morphological assessment for the Danube. LaRiMo represents an efficient and cost-effective approach to assess large river morphology across large extents. This method provides comparable results across countries and regions., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: The aim was to compare health-related quality-of-life (HRQOL) and cost-effectiveness between cytoreductive surgery with intraperitoneal chemotherapy (CRS + IPC) and systemic chemotherapy for patients with colorectal peritoneal metastases., Methods: Patients included in the Swedish Peritoneal Trial comparing CRS + IPC and systemic chemotherapy completed the EORTC QLQ-C30 and SF-36 questionnaires at baseline, 2, 4, 6, 12, 18, and 24 months. HRQOL at 24 months was the primary endpoint. EORTC sum score, SF-36 physical and mental component scores at 24 months were calculated and compared for each arm and then referenced against general population values. Two quality-adjusted life-year (QALY) indices were applied (EORTC-8D and SF-6D) and an incremental cost-effectiveness ratio (ICER) per QALY gained was calculated. A projected life-time ICER per QALY gained was calculated using predicted survival according to Swedish population statistics., Results: No statistical differences in HRQOL between the arms were noted at 24 months. Descriptively, survivors in the surgery arm had higher summary scores than the general population at 24 months, whereas survivors in the chemotherapy arm had lower scores. The projected life-time QALY benefit was 3.8 QALYs in favor of the surgery arm (p=0.06) with an ICER per QALY gained at 310,000 SEK (EORTC-8D) or 362,000 SEK (SF-6D) corresponding to 26,700-31,200 GBP., Conclusion: The HRQOL in patients with colorectal peritoneal metastases undergoing CRS + IPC appear similar to those receiving systemic chemotherapy. Two-year survivors in the CRS + IPC arm have comparable HRQOL to a general population reference. The treatment is cost-effective according to NICE guidelines., (Copyright © 2018 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Background: Epilepsy surgery for focal cortical dysplasia type II (FCD II) offers good chances for seizure freedom, but remains a challenge with respect to lesion detection, defining the epileptogenic zone and the optimal resection strategy. Integrating results from magnetic source imaging from magnetoencephalography (MEG) with magnetic resonance imaging (MRI) including MRI postprocessing may be useful for optimizing these goals., Methods: We here present data from 21 adult FCD II patients, investigated during a 10 year period and evaluated including magnetic source imaging. 16 patients had epilepsy surgery, i.e. histopathologically verified FCD II, and a long follow up. We present our analysis of epileptogenic zones including MEG in relation to structural data according to MRI data and relate these results to surgical outcomes., Results: FCD II in our cohort was characterized by high MEG yield and localization accuracy and MEG showed impact on surgical success-rates. MEG source localizations were detected in 95.2% of patients and were as close as 12.3 ± 8,1 mm to the MRI-lesion. After a mean follow up of >3 years, we saw >80% Engel I outcomes, with more favourable outcomes when the MEG source was completely resected (Fishers exact test 0,033)., Conclusion: We argue for a high value of conducting a combined MEG-MRI approach in the presurgical workup and the resection strategy in patients with FCD II related epilepsy.

Purpose: The incidence of epilepsy in older adults is growing, as does the incidence of comorbidities. Therefore, when it comes to epilepsy surgery in medically intractable epilepsy, age is often seen as a limiting factor. To investigate the outcome after epilepsy surgery in a population of older adults, we compared the benefit for patients aged 50-59 years with those aged 60 years and older in respect of efficacy and safety., Method: Patients aged ≥50 years with medically intractable epilepsy who underwent epilepsy surgery from 1990 to 2013 were selected from the database of a German epilepsy center. All of them received a standardised and detailed presurgical diagnostic evaluation. Follow-up included at least four scheduled visits with EEG, MRI and neuropsychological testing. Outcome was assessed using the Engel outcome scale., Results: 79 patients aged between 50 and 67 years were followed-up for a median of 4.7 years (2-16 years). 68% of patients were free of disabling seizures (Engel class I, ≥60 years: 75%) and 58% were seizure-free (Engel class IA, ≥60 years: 70%). 90% of our patients suffered from temporal lobe epilepsy (TLE), 9% from frontal lobe epilepsy (FLE) and one occipital lobe epilepsy (OLE). After surgery, 9% discontinued or tapered their medication. Permanent surgical complications occurred in 10% of cases and transient neurological deficits were seen in 11%. Older patients had a higher risk for postoperative hygroma (≥60 years 15%; <60 years 8%) and were more prone to postoperative memory deficits (≥60 years 45%), especially after resection of the dominant temporal lobe. Verbal and figural memory testing did not differ significantly between the groups., Conclusions: The results support the view that in selected older patients, epilepsy surgery shows equal or even higher success rates as compared to younger patients. However, patients of older age may be at greater risk for postoperative hygroma and memory deficits, especially after dominant temporal lobe resections., (Copyright © 2018 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Background: Bariatric procedures are increasingly being used, but data on bowel habits are scarce., Objectives: To assess changes in gastrointestinal function and patient-scored symptoms after Roux-en-Y gastric bypass (RYGB) and biliopancreatic diversion with duodenal switch (BPD/DS)., Setting: University hospital in Sweden., Methods: We recruited 268 adult patients (mean age of 42.5 yr, body mass index 44.8, 67.9% female) listed for RYGB and BPD/DS. Patients answered validated questionnaires prospectively concerning bowel function, the Fecal Incontinence Quality of Life Scale, and the 36-Item Short Form Health Survey before and after their operation., Results: Postoperatively, 208 patients (78.2% of 266 eligible patients) answered the questionnaires. RYGB patients had fewer bowel motions per week (8 versus 10) and more abdominal pain postoperatively (P<.001). Postoperatively, the 35 BPD/DS patients (69% versus 23%) needed to empty their bowel twice or more than twice daily, reported more flatus and urgency, and increased need for keeping a diet (P<.001). Concerning Fecal Incontinence Quality of Life Scale, coping and behavior was slightly reduced while depression and self-perception scores were improved after RYGB. Lifestyle, coping and behavior, and embarrassment were reduced after BPD/DS (P<.05). In the 36-Item Short Form Health Survey, physical scores were markedly improved, while mental scores were largely unaffected., Conclusion: RYGB resulted in a reduced number of bowel movements but increased problems with abdominal pain. In contrast, BPD/DS-patients reported higher frequency of bowel movements, more troubles with flatus and urgency, and increased need for keeping a diet. These symptoms affected quality of life negatively, however, general quality of life was markedly improved after both procedures. These results will be of great value for preoperative counseling., (Copyright © 2017 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.)

Background: There is an ongoing debate on the use of antibiotics instead of appendectomy for treating appendicitis but diagnostic difficulties and longstanding inflammation might lead to increased incidence of bowel cancer in these patients. The aim of this population-based study was to investigate the incidence of bowel cancer after non-surgical treatment of appendicitis., Patients and Methods: Patients diagnosed with appendicitis but lacking the surgical procedure code for appendix removal were retrieved from the Swedish National Inpatient Register 1987-2013. The cohort was matched with the Swedish Cancer Registry and the standardised incidence ratios (SIR) with 95% confidence interval (95% CI) for appendiceal, colorectal and small bowel cancers were calculated., Results: Of 13 595 patients with non-surgical treatment of appendicitis, 352 (2.6%) were diagnosed with appendiceal, colorectal or small bowel cancer (SIR 4.1, 95% CI 3.7-4.6). The largest incidence increase was found for appendiceal (SIR 35, 95% CI 26-46) and right-sided colon cancer (SIR 7.5, 95% CI 6.6-8.6). SIR was still elevated when excluding patients with less than 12 months since appendicitis and the incidence of right-sided colon cancer was elevated five years after appendicitis (SIR 3.5, 95% CI 2.1-5.4). An increased incidence of bowel cancer was found after appendicitis with abscess (SIR 4.6, 95% CI 4.0-5.2), and without abscess (SIR 3.5, 95% CI 2.9-4.1)., Conclusion: Patients with non-surgical treatment of appendicitis have an increased short and long-term incidence of bowel cancer. This should be considered in the discussion about optimal management of patients with appendicitis., (Copyright © 2017 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Hydropeaking as a result of peak-load electricity production has been identified as one of the most significant pressures in alpine streams. Scouring of macroinvertebrates leads to downstream transport of aquatic organisms (catastrophic drift). Additionally, invertebrates are affected by periodic drying of wetted area during the dewatering of gravel bars and exposed areas along the banks. Even though fish are physiologically better adapted to switch to suitable habitats, artificial flow fluctuations may be followed by lethal stranding and quick alteration in habitat quantity and quality. Nevertheless, the interactions between pressures on fish and macroinvertebrates in terms of hydropeaking have not been investigated so far. The aim of this paper is to evaluate effects of flow fluctuations on potential epibenthic feeding grounds. Therefore, we evaluated changes in habitat distribution resulting from rapid flow fluctuations in river reaches with different river morphological characteristics, for five different macroinvertebrate taxa. Additionally, microhabitats for brown trout at two different life stages were calculated using representative peaking events (seasonal analysis) based on mid- to long term times series. Moreover, GIS-analysis allowed the evaluation of hydropeaking impacts (interaction) on both, macroinvertebrates and fish. In this study, it could be documented that feeding from the benthos for juvenile and subadult brown trout is inhibited during peak flow and is therefore reduced to times of base flow. Moreover, potential benthic feeding areas occurring at base flow have been found to increase with the level of morphological heterogeneity within analyzed river reaches. Likewise, hydrological sensitivity testing in terms of reducing ∆Q at different levels was performed and revealed that possible positive effects required heterogeneous river morphology as a precondition. However, this approach might be applied for estimating the impacts of hydrological mitigation measures in hydropeaked rivers concerning physical condition and/or growth rate of salmonids considering the river morphology of the investigated stream., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Hydropeaking is one of the main pressures on the aquatic ecology in alpine rivers. Beside studies on abiotic process and biotic response on the local scale there is a lack in process understanding on the reach scale. Especially longitudinal changes of hydropeaking impacts based on retention processes have not been studied yet. Thus, based on unsteady one-dimensional and two-dimensional depth averaged modelling it was targeted to investigate possible changes in vertical ramping velocity for the discussion of possible mitigation measures at the local scale. Here, we compared artificial and natural sheltering habitats in terms of peak flow. Additionally, the hydropeaking assessment on various river scales was supported by an evaluation of tributaries in an alpine river system. Based on the modelling results and the discussion of the impact assessment of hydropeaking in different case studies we state, that on the first 5km downstream of the turbine outlet a significant decrease in vertical ramping velocity occurs. In this reach, habitat improvements should focus on increasing retention processes considering the higher risk of stranding for juvenile fish and macroinvertebrates. For morphological mitigation measures at the local scale, it turned out that self-formed, near-natural morphology should be targeted in terms of mitigation measure design compared to artificial sheltering habitats. Abundance and biomass of macroinvertebrates are directly linked to substrate variability in self-formed sheltering habitats downstream of gravel bars. Moreover, we ascertained that tributaries are able to contribute to the 'ecological potential' in multi-stressed hydropeaking rivers by providing spawning and rearing habitats for fish. However, for a sustainable improvement of the aquatic environment on all relevant scales, both sediment and flood dynamics have to be considered as important drivers to establish self-formed sheltering habitats in terms of hydropeaking., (Copyright © 2016. Published by Elsevier B.V.)

Artificial flow fluctuations due to the operation of hydropower plants, frequently described as hydropeaking, result in a constant decrease of biomass of specific macrozoobenthos (MZB) taxa. For the presented case study, we assessed three reaches in the Ziller River catchment. At each sampling reach we performed the Multi-Habitat-Sampling (MHS) method with a Water Framework Directive (WFD) compliant AQEM/MHS net according to the Austrian guideline. Additionally, a hydraulic-specific sampling was conducted with a modified Box (Surber) sampler. As a basis for predictive habitat modelling of the MZB fauna, we measured abiotic parameters like mean (v 40 ) and bottom-near (v bottom ) flow rate or water depth respectively, for each box sample. In addition, the choriotope type, representing grain size classes, was determined. One of the main results is, that the national status assessment was not capable to reflect the impact of pulse release at the investigated river stretches on the basis of status classes. Moreover, we figured out that 1) habitats of stagnophilic macroinvertebrate taxa are minimized in channelized stretches affected by hydropeaking, leading to heavy quantitative losses for populations, becoming apparent in significant decreases in total individual numbers and biomass for many taxa. 2) The minor respond of the ecological status class in affected stretches by applying the WFD compliant national assessment method for macroinvertebrates owes to the tolerance of rheobiont or rheophilic taxa commonly classified as indicators for good conditions regarding saprobity or degradation score. 3) A development of a stressor-specific sampling design is required as the MHS method largely ignores vulnerable habitats. 4) The habitat suitability of selected species provides efficient expertise for impact assessment and mitigation measure design in terms of predictive habitat modelling., (Copyright © 2016 Elsevier B.V. All rights reserved.)

The operation of storage hydropower plants is commonly linked to frequent fluctuations in discharge and water level (hydropeaking) of downstream river stretches and is often accompanied by cooling or warming of the water body downstream (cold or warm thermopeaking, respectively). The objective of this study is to assess the single and combined effects of hydropeaking and cold thermopeaking on the drift of selected aquatic macroinvertebrates in experimental flumes. The study specifically aims to (1) investigate the macroinvertebrate drift induced by hydropeaking, (2) identify taxon-specific drift patterns following combined hydropeaking and cold thermopeaking and (3) quantify diurnal drift differences under both impact types. Overall, hydropeaking induced significantly higher drift rates of most macroinvertebrate taxa. Combined hydropeaking and cold thermopeaking, however, revealed reduced total drift rates, however with strong taxon-specific response patterns. Hydropeaking during night led to significantly higher drift rates than during daytime, while in combination with thermopeaking the same trend was observable, although insignificant. Taxon-specific analysis revealed lower drift rates following hydropeaking for rheophilic and interstitial taxa (e.g. Leuctra sp., Hydropsyche sp.), whereas many limnophilic taxa adapted to low current showed markedly increased drift (e.g. Lepidostoma hirtum and Leptoceridae). In line with previous studies, our results confirm a significant loss of limnophilic macroinvertebrate taxa following hydraulic stress. The mitigating effect of cold thermopeaking might be explained by behavioural patterns, but requires further investigation to clarify if macroinvertebrates actively avoid drift and intrude into the interstitial, when cold water is discharged. Our results imply that river restoration projects must address the hydrological regime and, if necessary need to include suitable management schemes for hydropower plants. Besides operative management measures, the construction of reservoirs to buffer hydropeaks or the diversion of hydropeaks into larger water bodies could mitigate hydropeaking effects and foster biological recovery including limnophilic taxa., (Copyright © 2016 Elsevier B.V. All rights reserved.)

A key challenge for the ecological risk assessment of chemicals has been to evaluate the relative contribution of chemical pollution to the variability observed in biological communities, as well as to identify multiple stressor groups. In this study we evaluated the toxic pressure exerted by >200 contaminants to benthic macroinvertebrates in the Danube River using the Toxic Unit approach. Furthermore, we evaluated correlations between several stressors (chemical and non-chemical) and biological indices commonly used for the ecological status assessment of aquatic ecosystems. We also performed several variation partitioning analyses to evaluate the relative contribution of contaminants and other abiotic parameters (i.e. habitat characteristics, hydromorphological alterations, water quality parameters) to the structural and biological trait variation of the invertebrate community. The results of this study show that most biological indices significantly correlate to parameters related to habitat and physico-chemical conditions, but showed limited correlation with the calculated toxic pressure. The calculated toxic pressure, however, showed little variation between sampling sites, which complicates the identification of pollution-induced effects. The results of this study show that the variation in the structure and trait composition of the invertebrate community are mainly explained by habitat and water quality parameters, whereas hydromorphological alterations play a less important role. Among the water quality parameters, physico-chemical parameters such as suspended solids, nutrients or dissolved oxygen explained a larger part of the variation in the invertebrate community as compared to metals or organic contaminants. Significant correlations exist between some physico-chemical measurements (e.g. nutrients) and some chemical classes (i.e. pharmaceuticals, chemicals related to human presence) which constitute important multiple stressor groups. This study demonstrates that, in large rivers like the Danube, the variation in the invertebrate community seems to be more related to varying habitat and physico-chemical conditions than to chemical pollution., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: Various brain stimulation techniques are in use to treat epilepsy. These methods usually require surgical implantation procedures. Transcutaneous vagus nerve stimulation (tVNS) is a non-invasive technique to stimulate the left auricular branch of the vagus nerve at the ear conch., Objective: We performed a randomized, double-blind controlled trial (cMPsE02) to assess efficacy and safety of tVNS vs. control stimulation in patients with drug-resistant epilepsy., Methods: Primary objective was to demonstrate superiority of add-on therapy with tVNS (stimulation frequency 25 Hz, n = 39) versus active control (1 Hz, n = 37) in reducing seizure frequency over 20 weeks. Secondary objectives comprised reduction in seizure frequency from baseline to end of treatment, subgroup analyses and safety evaluation., Results: Treatment adherence was 84% in the 1 Hz group and 88% in the 25 Hz group, respectively. Stimulation intensity significantly differed between the 1 Hz group (1.02 ± 0.83 mA) and the 25 Hz group (0.50 ± 0.47 mA; p = 0.006). Mean seizure reduction per 28 days at end of treatment was -2.9% in the 1 Hz group and 23.4% in the 25 Hz group (p = 0.146). In contrast to controls, we found a significant reduction in seizure frequency in patients of the 25 Hz group who completed the full treatment period (20 weeks; n = 26, 34.2%, p = 0.034). Responder rates (25%, 50%) were similar in both groups. Subgroup analyses for seizure type and baseline seizure frequency revealed no significant differences. Adverse events were usually mild or moderate and comprised headache, ear pain, application site erythema, vertigo, fatigue, and nausea. Four serious adverse events were reported including one sudden unexplained death in epilepsy patients (SUDEP) in the 1 Hz group which was assessed as not treatment-related., Conclusions: tVNS had a high treatment adherence and was well tolerated. Superiority of 25 Hz tVNS over 1 Hz tVNS could not be proven in this relatively small study, which might be attributed to the higher stimulation intensity in the control group. Efficacy data revealed results that justify further trials with larger patient numbers and longer observation periods., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Cytoreductive surgery (CRS) plus perioperative intraperitoneal chemotherapy is a highly invasive treatment of peritoneal metastasis and requires many surgical procedures before mastering. The aim of this study was to estimate how many procedures are needed before stabilization can be seen in surgical outcome (R1 surgery, adverse events and bleeding) in patients with pseudomyxoma peritonei (PMP)., Patients and Methods: All 128 patients with PMP who were treated with CRS alone or CRS plus perioperative intraperitoneal chemotherapy between 2003 and 2008 at the Uppsala University Hospital, Uppsala, Sweden, were included. The learning curve was calculated using the partial least square (PLS) and cumulative sum control chart (CUSUM) graph. Two groups were formed based on the results of the learning curve. The learning curve plateau was considered the same as the stabilization in the CUSUM graph. Group I consisted of patients included during the learning period (n = 73) and Group II of patients treated after the learning period ended (n = 55). Comparisons between the groups were made on surgical outcome, survival and adverse events., Results: Stabilization was seen after 220 ± 10 procedures. A higher occurrence of R1 surgery was seen in Group II (80%) compared to Group I (48%; P = 0.0002). Overall survival increased at four years after surgery in Group II compared to Group I (80% vs. 63%; P = 0.02)., Conclusion: CRS plus perioperative intraperitoneal chemotherapy is a highly demanding procedure that requires more than 200 procedures before optimisation in surgical outcome is seen., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Objective: In a previous study we proposed a robust method for automatic seizure detection in scalp EEG recordings. The goal of the current study was to validate an improved algorithm in a much larger group of patients in order to show its general applicability in clinical routine., Methods: For the detection of seizures we developed an algorithm based on Short Time Fourier Transform, calculating the integrated power in the frequency band 2.5-12 Hz for a multi-channel seizure detection montage referenced against the average of Fz-Cz-Pz. For identification of seizures an adaptive thresholding technique was applied. Complete data sets of each patient were used for analyses for a fixed set of parameters., Results: 159 patients (117 temporal-lobe epilepsies (TLE), 35 extra-temporal lobe epilepsies (ETLE), 7 other) were included with a total of 25,278 h of EEG data, 794 seizures were analyzed. The sensitivity was 87.3% and number of false detections per hour (FpH) was 0.22/h. The sensitivity for TLE patients was 89.9% and FpH=0.19/h; for ETLE patients sensitivity was 77.4% and FpH=0.25/h., Conclusions: The seizure detection algorithm provided high values for sensitivity and selectivity for unselected large EEG data sets without a priori assumptions of seizure patterns., Significance: The algorithm is a valuable tool for fast and effective screening of long-term scalp EEG recordings., (Copyright © 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.)

Purpose: Optimized therapy in epilepsy should include individual care for cognitive functions. Here we introduce a computerized screening instrument, called "Computerized Cognitive Testing in Epilepsy" (CCTE), which allows for time-efficient repetitive assessment of the patient's cognitive profile regarding the domains of memory and attention, which are frequently impaired due to side effects of antiepileptic medication., Methods: The CCTE battery takes 30min and covers tasks of verbal and figural memory, cognitive speed, attention and working memory. The patient's results are displayed immediately in comparison to age-related normative data. For evaluation of psychometrics and clinical correlations, data from patients of a tertiary referral epilepsy center (n=240) and healthy subjects (n=83) were explored., Results: CCTE subtests show good reliability and concurrent validity compared to standard neuropsychological tests (p<0.01). Adverse cognitive effects of antiepileptic medication can be detected (p<0.05), e.g. significant negative effects of increasing drug load. Specific epilepsy subgroups, e.g. focal versus primary generalized epilepsy or right versus left mesial temporal lobe epilepsy, showed different CCTE profiles., Conclusion: CCTE appears valuable for early detection of individual cognitive alterations related to medication. In addition, it displays interesting differences between epilepsy syndromes. The CCTE battery provides a standardized, time- and personnel-efficient assessment of cognitive functions open to a large number of patients and applicable for clinical and scientific use in epilepsy., (Copyright © 2012 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Background: The aim of this study was to compare debulking surgery and cytoreductive surgery (CRS) in patients with Pseudomyxoma peritonei (PMP) regarding efficacy and safety., Patients and Methods: Data were extracted from medical records and treatment outcomes were analyzed for all 152 patients with PMP who were scheduled for debulking surgery and intraperitoneal chemotherapy (IPC) or CRS and IPC at Uppsala University Hospital, Uppsala, Sweden, between September 1993 and December 2008., Results: One hundred and ten patients (73%) were treated with CRS and IPC and 40 (27%) with debulking surgery and IPC. In two patients (1%), surgery was defined as open and close. Patients with CRS and IPC had a 74% 5-year overall survival (OS) rate compared with 40% for those treated with debulking surgery (P < 0.001). Patients with no residual macroscopic tumour (R1 resection) had a better 5-year OS rate of 94% compared with 28% for patients with macroscopic residual tumour (R2) (P < 0.001). Grades II-IV adverse events were seen in 29% of debulked patients and in 47% of CRS/IPC patients (P = 0.053)., Conclusions: CRS and IPC seems more efficient than debulking surgery and IPC but with numerically higher morbidity. Therefore, if surgically possible, CRS should be the treatment of choice for PMP patients. However, debulking surgery may still be of benefit to selected patients for palliative purposes., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Background: Cytoreductive surgery (CRS) and intraperitoneal chemotherapy (IPC) treatment of colorectal peritoneal carcinomatosis (PC) is gaining acceptance, but controversy remains. The primary aims were to analyse the outcome and prognostic variables of colorectal PC patients treated with CRS and IPC, and to report on the outcome of additional surgical treatments of subsequent recurrences., Methods: Patients referred for treatment of colorectal PC between 1996 and 2010 were included in a cohort. The following data was collected: clinicopathological parameters, survival, recurrences, perioperative chemotherapy and type of IPC (hyperthermic intraperitoneal chemotherapy, HIPEC; or sequential postoperative intraperitoneal chemotherapy, SPIC). Multivariable analyses were conducted on potential prognostic factors for overall survival (OS)., Results: In the 151-patient cohort, the median OS was 34 months (range: 2-77) for CRS and HIPEC with five-year survival predicted at 40% (five-year disease-free survival 32%). For CRS and SPIC, the OS was 25 months (range: 2-188) with five-year survival at 18%. Open-and-close patients survived 6 months (range: 0-14) with no five-year survival (HIPEC vs. SPIC p = 0.047, SPIC vs. open-and-close p < 0.001). Adjuvant systemic chemotherapy was a noteworthy independent prognostic factor in the multivariable analysis. OS for patients undergoing additional surgical treatment of recurrences was 25 months vs. 10 months with best supportive care or palliative chemotherapy (p = 0.01)., Conclusion: Substantial long-term survival is possible in patients with colorectal PC. HIPEC was associated with better OS than SPIC and adjuvant systemic chemotherapy may improve the outcome in patients. Good OS is achievable in selected patients undergoing additional surgical treatment of isolated liver or peritoneal recurrences after prior complete CRS., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Background: Cytoreductive surgery and intraperitoneal chemotherapy has improved prognosis in patients with peritoneal carcinomatosis. The main modes of intraperitoneal chemotherapy treatment are peroperative hyperthermic intraperitoneal chemotherapy (HIPEC) and normothermic sequential postoperative intraperitoneal chemotherapy (SPIC). The aim of this study was to compare HIPEC and SPIC with respect to overall survival, disease-free survival, morbidity, and mortality in patients with peritoneal carcinomatosis from colon cancer., Patients and Methods: A matched case-control study was conducted in patients with surgical macroscopic complete removal of carcinomatosis; matching was according to the peritoneal cancer index score. Thirty-two patients were included, 16 in each group (HIPEC and SPIC). Overall survival, disease-free survival, morbidity, mortality, and clinicopathological parameters were compared., Results: Median overall survival was 36.5 months in the HIPEC group and 23.9 months in the SPIC group (P = 0.01). Median disease-free survival for these groups was 22.8 (HIPEC) and 13.0 months (SPIC; P = 0.02). Morbidity was not statistically different, 19% in SPIC and 37% in HIPEC. Postoperative mortality was observed in one patient in each group., Conclusion: HIPEC was associated with improved overall survival and disease-free survival compared with SPIC at similar morbidity and mortality, suggesting that HIPEC is the treatment of choice in colonic peritoneal carcinomatosis.

Background: Injection of a bulking agent in the anal canal is an increasingly used treatment for faecal incontinence, but efficacy has not been shown in a controlled trial. We aimed to assess the efficacy of injection of dextranomer in stabilised hyaluronic acid (NASHA Dx) for treatment of faecal incontinence., Methods: In this randomised, double-blind, sham-controlled trial, patients aged 18-75 years from centres in USA and Europe were randomly assigned (2:1) to receive either transanal submucosal injections of NASHA Dx or sham injections. Randomisation was stratified by sex and region in blocks of six, and managed with a computer generated, real-time, web-based system. Patients and investigators were masked to assignment for 6 months when the effect on severity of faecal incontinence and quality of life was assessed with a 2-week diary and clinical assessments. The primary endpoint was response to treatment based on the number of incontinence episodes. A response to treatment was defined as a reduction in number of episodes by 50% or more. Patients in the active treatment group are still being followed up. This trial was registered with ClinicalTrials.gov, number NCT00605826., Findings: 278 patients were screened for inclusion, of whom 206 were randomised assigned to receive NASHA Dx (n=136) or sham treatment (n=70). 71 patients who received NASHA Dx (52%) had a 50% or more reduction in the number of incontinence episode, compared with 22 patients who received sham treatment (31%; odds ratio 2·36, 95% CI 1·24-4·47, p=0·0089). We recorded 128 treatment-related adverse events, of which two were serious (1 rectal abscess and 1 prostatic abscess)., Interpretation: Anal injection of NASHA Dx is an effective treatment for faecal incontinence. A refinement of selection criteria for patients, optimum injected dose, ideal site of injection, and long-term results might further increase the acceptance of this minimally invasive treatment., Funding: Q-Med AB., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

A reliable method for the estimation of seizure frequency and severity is indispensable in assessing the efficacy of drug treatment in epilepsies. These quantities are usually deduced from subjective patient reports, which may cause considerable problems due to insufficient or false descriptions of seizures and their frequency. We present data from two difficult-to-treat patients with intractable epilepsy. Pat. 1 has had an unknown number of CP seizures. Here, a prolonged outpatient video-EEG monitoring over 160 h and 137 h (over an interval of three months) was performed with an automated seizure detection method. Pat. 2 suffered exclusively from nocturnal seizures originating from the frontal lobe. In this case, an objective quantification of the efficacy of drug treatment over a time period of 22 weeks was established. For the reliable quantification of seizures, a prolonged outpatient video/video-EEG monitoring was appended after a short-term inpatient monitoring period. Patient 1: The seizure detection algorithm was capable of detecting 10 out of 11 seizures. The number of false-positive events was <0.03/h. It was clearly demonstrated that the patient showed more seizures than originally reported. Patient 2: The add-on medication of lacosamide led to a significant reduction in seizure frequency and to a marked decrease in the mean duration of seizures. The severity of seizures was reduced from numerous hypermotoric seizures to few mild, head-turning seizures. Outpatient monitoring may be helpful to guide treatment for severe epilepsies and offers the possibility to more reliably quantify the efficacy of treatment in the long-term, even over several months., (Copyright © 2010 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Background: Peritoneal carcinomatosis (PC) is fatal without special combined cytoreductive surgery (CRS) and intraperitoneal chemotherapy (IPC). This study was designed to identify factors that may increase the risk of postoperative morbidity and mortality from combined CRS and IPC interventions for PC. Survival based on primary tumour type and extent of surgery is reported., Methods: Between May 1991 and November 2004, 123 patients were treated with CRS and IPC for PC. Based on the National Cancer Institute Common Toxicity Criteria for grade 3 and 4, data on 30 days postoperative morbidity and 90 days mortality were analysed., Results: Grade 3-4 adverse events were observed in 51 patients (41%) and were associated with stoma formation, duration of surgery, peroperative blood loss and peritoneal cancer index (PCI). Excision, or electrocautery evaporation, of tumour from small bowel surface was correlated to bowel morbidity. Five patients had treatment-related mortality (4%) within 90 days. Survival was associated with macroscopic radical surgery, prior surgical score, PCI and primary tumour type., Conclusions: CRS and IPC for PC are associated with high morbidity and mortality. However, in light of the potential benefit indicated by long-term survival, the adverse event from this treatment is considered acceptable.

Aims: To investigate if the pattern of cytotoxic drug sensitivity in vitro in patient samples of peritoneal carcinomatosis (PC) is supportive to the current standardized approach for drug selection for perioperative intraperitoneal chemotherapy (IPC)., Methods: The cytotoxic effect of cisplatin, oxaliplatin, irinotecan, 5-fluorouracil, mitomycin-C, doxorubicin and melphalan was investigated in vitro on tumour cells from 223 patient tumour samples of different PC origins., Results: Considerable differences in cytotoxic drug sensitivity between tumour types of the PC entity and within each tumour type were observed. Cisplatin showed high cross-resistance with oxaliplatin but low cross-resistance with doxorubicin and irinotecan. No cross-resistance was found between irinotecan and doxorubicin. The dose-response relationships for melphalan and irinotecan in individual samples showed great variability., Conclusions: The activity in vitro of cytotoxic drugs commonly used in IPC for PC is very heterogeneous. Efforts for individualizing drug selection for PC patients undergoing IPC seem justified.

Background: The extent to which chemotherapy may relieve tumour-related symptoms, improve quality of life and prolong survival in patients with gastric cancer is not known in spite of the extensive use of this treatment modality. The aim of this study was to estimate any gain in the quantity and quality of life produced by chemotherapy in these patients., Patients and Methods: Between January 1991 and February 1995, 61 patients with gastric cancer were randomized to either chemotherapy in addition to best supportive care or to best supportive care. Chemotherapy was allowed in the latter group if the supportive measures did not lead to palliation. Chemotherapy was the ELF-regimen consisting of 5-fluorouracil, leucovorin and etoposide, or, in elderly patients with poor performance, a 5-fluorouracil/leucovorin regimen (FLv). Quality of life was evaluated with the EORTC-QLQ-C30 instrument., Results: More patients in the chemotherapy group (45%, 14/31) had an improved or prolonged high quality of life for a minimum period of 4 months compared to those in the best supportive care group (20%, 6/30, P < 0.05). A similar difference was seen in the treating physician's evaluation of whether the patient was subjectively improved or continued to do well for at least 4 months (17/31, 55% versus 6/30, 20%, P < 0.01). Overall survival was longer in the chemotherapy group (median 8 vs. 5 months) although the difference was not statistically significant (P = 0.12). After corrections for imbalances in pretreatment characteristics, chemotherapy treatment was, however, associated with a survival benefit (P = 0.003). Also, the quality-adjusted survival time and time to disease progression were longer for patients randomized to chemotherapy (median 5 vs. 2 months, P = 0.03)., Conclusions: The results show that chemotherapy can add to both quantity and quality of life in advanced gastric cancer. The number of patients who benefit from treatment is, however, still rather limited.

Background: Chemotherapy may relieve tumor-related symptoms, may improve quality of life and prolong survival in advanced gastrointestinal cancer. The extent of such improvements is unclear despite the extensive use of this treatment modality, and there are no studies concerning the economic cost of any gain achieved in the quantity and quality of life by chemotherapy., Patients and Methods: Between January 1991 and May 1992, 61 patients with inoperable cancer (18 gastric, 22 pancreatic or biliary, and 21 colorectal) were randomized to either primary chemotherapy in addition to best supportive care or to best supportive care. Chemotherapy was allowed in the latter group if the supportive measures did not achieve palliation. All economic costs for medical care were prospectively recorded, and marginal cost-effectiveness analyses were performed., Results: More patients in the primary chemotherapy group (19/33, 58%) had improved/prolonged high quality of life (QoL-patient, minimum duration 4 months) than in the best supportive care group (8/28, 29%, p < 0.05). Overall survival and quality-adjusted survival were significantly longer in the primary chemotherapy group (median 9 vs. 4 months, p < 0.05), and median 7 vs. 2 months, p < 0.05, respectively). When analysed by cancer site, survival was significantly prolonged in gastric cancer patients (median 10 vs. 4 months, p < 0.02), but not in colorectal (median 12 vs. 6 months, p = 0.1) and pancreatic-biliary cancer patients (median 8 vs. 5 months, p = 0.8). The average cost for all medical care was approximately 50% higher in the primary chemotherapy group, but the average cost per day was the same in the two groups. Hospitalization accounted for most of the costs in both groups. The incremental costs per gained year of life was SEK 166,400 ($21,300), per gained quality-adjusted year of life SEK 157,200 ($20,200), and per QoL-patient SEK 160,300 ($20,600). These costs were lower for gastric and colorectal cancer patients, and much higher for pancreatic-biliary cancer patients., Conclusions: The results of this study suggest that palliative chemotherapy is cost-effective in patients with advanced gastric and colorectal cancer. Knowledge about survival and quality of life benefits is still limited in patients suffering from gastric and pancreatic-biliary cancer.

Motor control of different segments of the body with multiple degrees of freedom appears to be coordinated by utilizing preferred axes of motor activity. This hypothesis may also be applied to vestibular control of posture. To explore this question we studied the anatomical relationship between the head and the cervical vertebral column by taking radiographs of the head-neck region in unrestrained alert guinea pigs. We determined that biomechanical constraints contribute to the stereotypical skeletal geometry observed in the resting animal and to a functional segmentation of the head-neck movement apparatus. Subsequent lesion studies of vestibular end organs with quantification of the resulting postural syndromes suggest that the functional segmentation of the cervical vertebral column corresponds to a functional partitioning of vestibular afferents. Our findings also indicate that the sensorimotor transformation mechanisms necessary to convert a given head velocity signal into the appropriate neck motor frame are already embedded in the networks provided by second-order vestibular neurons. Good trim of postural control will be the end result of an appropriate internal representation of the objective vertical.

Hepatic metastases were induced in nude rats by intraportal injection of 2.5-5.0 x 10(6) cells from the human colonic cancer cell line LS 174 T. Quantification of tumour burden, expressed as relative metastatic area, was performed by contrast-enhanced computed tomography (CT) scanning in vivo (n = 14), contrast enhanced CT scanning post mortem (n = 21) and computer-based area calculation (CBAC) (n = 21). To determine the false-positive contribution to the estimated tumour burden by the evaluation procedures themselves, six rats without metastases were assessed. The quantification in the three different assessment groups was in close accordance in animals with an intermediate or extensive metastatic burden, but not in rats with a minor (< 4%) tumour burden. The results indicate that contrast-enhanced CT scanning can be used in this model to quantify hepatic metastases, except in animals with few and small lesions. Furthermore, the results suggest a potential for the assessment of therapeutic response by repeated contrast-enhanced CT scanning in vivo, as well as prospects for a corresponding evaluation in man.

Nude rats were injected with human colonic cancer cells (LS 174 T) in the superior mesenteric vein and the extent of hepatic metastases at sacrifice was estimated by visual inspection and computer-based area calculation. After 3 weeks, 5.0 x 10(6) cells caused hepatic metastases in 14/14 rats whereas 0.5 x 10(6) cells failed to produce liver metastases in 4/4 rats (P < 0.001). Injection of 1.0 x 10(7) cells caused portal vein occlusion in 3/5 rats. Extrahepatic tumour growth was rare; lung metastases were observed in four rats, and three rats had local tumour in the abdomen. The average extent of hepatic tumour replacement was 20.2 +/- 4.0%. Injection of embolies or single cells did not affect the incidence or extent of hepatic metastases. The incidence of hepatic metastases was similar in male and female rats, but the extent of hepatic tumour was larger in males (24.6%) than in females (3.2%) (P = 0.005). The pathophysiological similarities to human disease should make this model suitable for diagnostic and therapeutic studies with clinical application.

The climbing fibres (CFs) of the rabbit flocculus that respond in a speed- and direction-selective manner to retinal image slip produced by eye rotations can be divided into three classes on the basis of the orientation of the rotation axis associated with their greatest modulation (the preferred axis). The similarity of the orientations of these axes to those of the eye rotation axes of the extraocular muscles suggests that a simple geometrical correspondence may exist between the eye rotation associated with the preferred axis of a given class of CFs and the eye rotation produced by activation of the Purkinje cells upon which that class of CFs synapse. To pursue this possibility, the axes of the eye rotations evoked by electrical microstimulation of the alert rabbit's flocculus were determined simultaneously for both eyes in three dimensions using two orthogonal search coils on each eye. A limited number of slow eye movement response patterns were found, and of these, two predominated. The most common response was a counterclockwise (CCW) rotation of the ipsilateral (left) eye around an axis close to the horizontal plane and at about 140 degrees posterior to the nose. The other predominant response was abduction of the ipsilateral eye. These two response patterns, together with the smaller conjugate components for the contralateral eye, are consonant with the orientations of the preferred CF axes. In addition, a clear CCW rotation of the contralateral (right) eye about its 135 degrees axis was also evoked from some stimulation sites. This response, which occurred either alone or as a component of an upward rotation about the nasal-occipital (roll) axis, is at variance with the orientations of the preferred CF axis. However, the latencies of the CCW contralateral 135 degrees component (80-140 ms) were greater than those of the CW contralateral 45 degrees component, the CCW ipsilateral 135 degrees component and the ipsilateral abduction component (8-48 ms). These latency differences may distinguish stimulation of Purkinje cells from stimulation of other neurones.

A synopsis of physiological and anatomical results is presented that leads to the conclusion that experimental data have to be interpreted in a context meaningful for the system investigated. For example, since there is an obvious spatial relationship between semicircular canals and extraocular muscles, the interdependence between the three-neurone-arc circuitry, and vestibular and visual signals follows quite naturally from a common geometry inherent in the sensory and motor periphery. It is emphasized that signals related to compensatory eye movements have to be interpreted within a vestibular/eye muscle frame of reference. By the same argument, when dealing with the head-neck movement system, the appropriate reference frame will have to be applied to arrive at a meaningful interpretation of related sensorimotor functions. Thus, in general terms, each system has to be interpreted within its own meaningful biological context.