Accurate population-based model for individual prediction of colon cancer recurrence.

BACKGROUND: Prediction models are useful tools in the clinical management of colon cancer patients, particularly when estimating the recurrence rate and, thus, the need for adjuvant treatment. However, the most used models (MSKCC, ACCENT) are based on several decades-old patient series from clinical trials, likely overestimating the current risk of recurrence, especially in low-risk groups, as outcomes have improved over time. The aim was to develop and validate an updated model for the prediction of recurrence within 5 years after surgery using routinely collected clinicopathologic variables. MATERIAL AND METHODS: A population-based cohort from the Swedish Colorectal Cancer Registry of 16,134 stage I-III colon cancer cases was used. A multivariable model was constructed using Cox proportional hazards regression. Three-quarters of the cases were used for model development and one quarter for internal validation. External validation was performed using 12,769 stage II-III patients from the Norwegian Colorectal Cancer Registry. The model was compared to previous nomograms. RESULTS: The nomogram consisted of eight variables: sex, sidedness, pT-substages, number of positive and found lymph nodes, emergency surgery, lymphovascular and perineural invasion. The area under the curve (AUC) was 0.78 in the model, 0.76 in internal validation, and 0.70 in external validation. The model calibrated well, especially in low-risk patients, and performed better than existing nomograms in the Swedish registry data. The new nomogram's AUC was equal to that of the MSKCC but the calibration was better. CONCLUSION: The nomogram based on recently operated patients from a population registry predicts recurrence risk more accurately than previous nomograms. It performs best in the low-risk groups where the risk-benefit ratio of adjuvant treatment is debatable and the need for an accurate prediction model is the largest.

Transanal total mesorectal excision for rectal cancer has been suspended in Norway.

BACKGROUND: Transanal total mesorectal excision (TaTME) for rectal cancer has emerged as an alternative to the traditional abdominal approach. However, concerns have been raised about local recurrence. The aim of this study was to evaluate local recurrence after TaTME. Secondary aims included postoperative mortality, anastomotic leak and stoma rates. METHODS: Data on all patients who underwent TaTME were recorded and compared with those from national cohorts in the Norwegian Colorectal Cancer Registry (NCCR) and the Norwegian Registry for Gastrointestinal Surgery (NoRGast). Kaplan-Meier estimates were used to compare local recurrence. RESULTS: In Norway, 157 patients underwent TaTME for rectal cancer between October 2014 and October 2018. Three of seven hospitals abandoned TaTME after a total of five procedures. The local recurrence rate was 12 of 157 (7·6 per cent); eight local recurrences were multifocal or extensive. The estimated local recurrence rate at 2·4 years was 11·6 (95 per cent c.i. 6·6 to 19·9) per cent after TaTME compared with 2·4 (1·4 to 4·3) per cent in the NCCR (P < 0·001). The adjusted hazard ratio was 6·71 (95 per cent c.i. 2·94 to 15·32). Anastomotic leaks resulting in reoperation occurred in 8·4 per cent of patients in the TaTME cohort compared with 4·5 per cent in NoRGast (P = 0·047). Fifty-six patients (35·7 per cent) had a stoma at latest follow-up; 39 (24·8 per cent) were permanent. CONCLUSION: Anastomotic leak rates after TaTME were higher than national rates; local recurrence rates and growth patterns were unfavourable.

ANTECEDENTES: La resección total del mesorrecto transanal (transanal total mesorectal excision, TaTME) para el cáncer de recto se ha propuesto como una alternativa al abordaje abdominal tradicional. Sin embargo, la recidiva local (local recurrence, LR) después de este procedimiento es motivo de preocupación. El objetivo de este estudio fue evaluar la LR en pacientes operados mediante TaTME. Los objetivos secundarios incluyeron la mortalidad postoperatoria, las fugas anastomóticas y el porcentaje de estomas. MÉTODOS: Se registraron los datos de todos los pacientes operados mediante TaTME y se compararon con las cohortes nacionales del Registro Noruego de Cáncer Colorrectal (Norwegian Colorectal Cancer Registry, NCCR) y del Registro Noruego de Cirugía Gastrointestinal (Norwegian Registry for Gastrointestinal Surgery, NoRGast) utilizando estimaciones de Kaplan-Meier y la prueba de log-rank para comparar curvas de LR. RESULTADOS: En Noruega, 157 pacientes se sometieron a TaTME por cáncer de recto entre octubre de 2014 y octubre de 2018. Tres de siete hospitales abandonaron el TaTME después de un total de cinco procedimientos. La LR observada fue 12/157 (7,6%), siendo ocho de ellas multifocales o extensas. La tasa estimada de LR a 2,4 años fue de 11,6 % (i.c. del 95% 6,6 a 19,9) versus 2,4 % (1,4 a 4,3) en el NCCR (log rank P < 0,001). El cociente de riesgos instantáneos (hazard ratio, HR) ajustado fue 6,7 (i.c. del 95% 2,9 a 15,3). Las fugas anastomóticas que precisaron una reintervención después de TaTME ocurrieron en un 8,4% versus 4,5% en el registro NoRGast (P = 0,047). Cincuenta y seis pacientes (35,7%) tenían un estoma en el último seguimiento; 39 (24,8%) eran permanentes. CONCLUSIÓN: Las tasas de fuga anastomótica tras una TaTME fueron más altas que los datos nacionales con tasas de LR y patrones de crecimiento desfavorables.

Anastomotic leak after surgery for colon cancer and effect on long-term survival.

AIM: An anastomotic leak after surgery for colon cancer is a recognized complication but how it may adversely affect long-term survival is less clear because data are scarce. The aim of the study was to investigate the long-term impact of Grade C anastomotic leak in a large, population-based cohort. METHOD: Data on patients undergoing resection for Stage I-III colon cancer between 2008 and 2012 were collected from the Swedish, Norwegian and Danish Colorectal Cancer Registries. Overall relative survival and conditional 5-year relative survival, under the condition of surviving 1 year, were calculated for all patients and stratified by stage of disease. RESULTS: A total of 22 985 patients were analysed. Anastomotic leak occurred in 849 patients (3.7%). Five-year relative survival in patients with anastomotic leak was 64.7% compared with 87.0% for patients with no leak (P < 0.001). Five-year relative survival among the patients who survived the first year was 88.6% vs 81.3% (P = 0.003). Stratification by cancer stage showed that anastomotic leak was significantly associated with decreased relative survival in patients with Stage III disease (P = 0.001), but not in patients with Stage I or II (P = 0.950 and 0.247, respectively). CONCLUSION: Anastomotic leak after surgery for Stage III colon cancer was associated with significantly decreased long-term relative survival.

Short-term outcomes after elective colon cancer surgery: an observational study from the Norwegian registry for gastrointestinal and HPB surgery, NoRGast.

BACKGROUND: To describe the real burden of major complications after elective surgery for colon cancer in Norway, and to assess which predictors that are significantly associated with the short-term outcome. METHODS: An observational, multi-centre analysis of prospectively registered colon resections registered into the Norwegian Registry for Gastrointestinal Surgery, NoRGast, between January 2014 and December 2016. A propensity score-adjusted subgroup analysis for surgical access groups was attempted, with laparoscopic resections grouped as intention-to-treat. RESULTS: Out of 1812 resections, 14.0% of patients experienced a major complication within 30 days following surgery. The over-all reoperation rate was 8.7%, and rate of reoperation for anastomotic leak was 3.8%. Twenty patients (1.1%) died within 30 days after surgery. Higher age was not a significant predictor of major complications, including 30-day mortality. After correction for all co-variables, open access surgery was associated with higher rates of major complications (OR 1.67 (CI 1.22-2.29), p = 0.002), higher 30-day mortality (OR 4.39 (CI 1.19-16.13) p = 0.026) and longer length-of-stay (HR 0.58 (CI 0.52-0.65) p < 0.001). CONCLUSIONS: Our results indicate a low complication burden and high rate of uneventful patient journeys after elective surgery for colon cancer in Norway. Age was not associated with higher morbidity or mortality rates. Open access surgery was associated with an inferior short-term outcome.

Observation of a Goos-Hänchen-like Phase Shift for Magnetostatic Spin Waves.

In optics, a light beam experiences a spatial shift in the beam plane upon total internal reflection. This shift is usually referred to as the Goos-Hänchen shift. When dealing with plane waves, it manifests itself as a phase shift between an incoming and reflected wave that depends on the wave vector component along the interface. In the experiments presented here, plane spin waves are excited in a 60-nm-thick Permalloy film and propagate towards the edge of the film. By means of time-resolved scanning Kerr microscopy, we are able to directly detect a phase shift between the incoming and reflected wave. With the help of a numerical model, we show that this phase shift naturally occurs for spin waves in the dipolar regime.

One-year results of the SCANDIV randomized clinical trial of laparoscopic lavage versus primary resection for acute perforated diverticulitis.

BACKGROUND: Recent randomized trials demonstrated that laparoscopic lavage compared with resection for Hinchey III perforated diverticulitis was associated with similar mortality, less stoma formation but a higher rate of early reintervention. The aim of this study was to compare 1-year outcomes in patients who participated in the randomized Scandinavian Diverticulitis (SCANDIV) trial. METHODS: Between February 2010 and June 2014, patients from 21 hospitals in Norway and Sweden presenting with suspected perforated diverticulitis were enrolled in a multicentre RCT comparing laparoscopic lavage and sigmoid resection. All patients with perforated diverticulitis confirmed during surgery were included in a modified intention-to-treat analysis of 1-year results. RESULTS: Of 199 enrolled patients, 101 were assigned randomly to laparoscopic lavage and 98 to colonic resection. Perforated diverticulitis was confirmed at the time of surgery in 89 and 83 patients respectively. Within 1 year after surgery, neither severe complications (34 versus 27 per cent; P = 0·323) nor disease-related mortality (12 versus 11 per cent) differed significantly between the lavage and surgery groups. Among the 144 patients with purulent peritonitis, the rate of severe complications (27 per cent (20 of 74) versus 21 per cent (15 of 70) respectively; P = 0·445) and disease-related mortality (8 versus 9 per cent) were similar. Laparoscopic lavage was associated with more deep surgical-site infections (32 versus 13 per cent; P = 0·006) but fewer superficial surgical-site infections (1 versus 17 per cent; P = 0·001). More patients in the lavage group underwent unplanned reoperations (27 versus 10 per cent; P = 0·010). Including stoma reversals, a similar proportion of patients required a secondary operation (28 versus 29 per cent). The stoma rate at 1 year was lower in the lavage group (14 versus 42 per cent in the resection group; P < 0·001); however, the Cleveland Global Quality of Life score did not differ between groups. CONCLUSION: The advantages of laparoscopic lavage should be weighed against the risk of secondary intervention (if sepsis is unresolved). Assessment to exclude malignancy (although uncommon) is advised. Registration number: NCT01047462 ( http://www.clinicaltrials.gov).

Time Resolved Measurements of the Switching Trajectory of Pt/Co Elements Induced by Spin-Orbit Torques.

We report the experimental observation of spin-orbit torque induced switching of perpendicularly magnetized Pt/Co elements in a time resolved stroboscopic experiment based on high resolution Kerr microscopy. Magnetization dynamics is induced by injecting subnanosecond current pulses into the bilayer while simultaneously applying static in-plane magnetic bias fields. Highly reproducible homogeneous switching on time scales of several tens of nanoseconds is observed. Our findings can be corroborated using micromagnetic modeling only when including a fieldlike torque term as well as the Dzyaloshinskii-Moriya interaction mediated by finite temperature.

Snell's Law for Spin Waves.

We report the experimental observation of Snell's law for magnetostatic spin waves in thin ferromagnetic Permalloy films by imaging incident, refracted, and reflected waves. We use a thickness step as the interface between two media with different dispersion relations. Since the dispersion relation for magnetostatic waves in thin ferromagnetic films is anisotropic, deviations from the isotropic Snell's law known in optics are observed for incidence angles larger than 25° with respect to the interface normal between the two magnetic media. Furthermore, we can show that the thickness step modifies the wavelength and the amplitude of the incident waves. Our findings open up a new way of spin wave steering for magnonic applications.

Compliance with enhanced recovery after surgery criteria and preoperative and postoperative counselling reduces length of hospital stay in colorectal surgery: results of a randomized controlled trial.

AIM: The aim of this randomized clinical trial was to compare patients treated using a multimodal approach [enhanced recovery after surgery (ERAS)], with a special focus on counselling, to patients treated in a standard conventional care pathway, who underwent elective colorectal resection. METHOD: In a single-centre trial, adult patients eligible for open or laparoscopic colorectal resection were randomized to an ERAS programme or standard care. The primary end-point was postoperative total hospital stay. Identical discharge criteria were defined for both treatment groups. Secondary end-points included postoperative complications, postoperative C-reactive protein levels, postoperative hospital stay, readmission rate and mortality. All parameters were recorded before operation, on the day of surgery and daily thereafter until discharge. RESULTS: Total hospital stay was significantly shorter among patients randomized to ERAS than among the standard group [median 5 days (range 2-50 days) vs median 8 days (range 2-48 days); P = 0.001]. The two treatment groups exhibited similar outcomes regarding overall major and minor morbidity, reoperation rate, readmission rate and 30-day mortality. There were also no differences in tolerance of enteral nutrition or in the inflammatory response, as reflected by postoperative C-reactive protein levels. CONCLUSION: ERAS care was associated with a significantly shorter length of hospital stay. Without any difference in surgical or general complications, tolerance of enteral nutrition or postoperative C-reactive protein levels, peri-operative information and guidance for ensuring that patients comply with the ERAS approach appear to be important factors to reduce the length of hospital stay.

CCR7 facilitates the pro-inflammatory function of dendritic cells in experimental leishmaniasis.

Cutaneous leishmaniasis, caused by the parasite Leishmania major, results in lesions at the site of infection, which are self-healing in resistant hosts. However, in the absence of the chemokine receptor CCR7, mice are unable to heal the lesion and develop chronic disease. These B6.CCR7(-/-) mice display an increased number of Th2 cells and immunosuppressive cytokine levels, as well as more regulatory T cells. As CCR7 is expressed on activated dendritic cells (DCs), and these cells require CCR7 to migrate to the draining lymph node, we expected decreased migration of DCs into the lymph node in the absence of CCR7 during cutaneous leishmaniasis. Consequently, in an attempt to initiate a self-healing response, we adoptively transferred CCR7(+) (B6.WT) DCs into the site of infection of B6.CCR7(-/-) mice. Surprisingly, instead of healing the lesion, B6.CCR7(-/-) mice inoculated with B6.WT DCs developed augmented lesions and showed increased immunosuppression compared to control B6.CCR7(-/-) mice transferred with B6.CCR7(-/-) DCs or B6.WT mice with B6.WT DCs. Finally, B6.WT mice injected with B6.CCR7(-/-) DCs also presented delayed healing of the lesion. These results indicate that CCR7 must be expressed on DCs, as well as peripheral cells, to allow an efficient immune response to L. major.

[Red flags in the diagnostics of back pain]. / "Red flags" in der Diagnostik von Rückenschmerzen.

BACKGROUND: Low back pain is one of the most commonly occurring symptomatic complaints with a lifetime prevalence of 70 %. OBJECTIVE: The question of meaningful radiological diagnostics arises in connection with the diagnostics and treatment of low back pain as the common lead symptom. MATERIAL AND METHODS: Special clinical warning signs, so-called red flags, which are indicative of a specific cause of low back pain and of the necessity for possible treatment, are presented with special reference to the national treatment guidelines on low back pain. RESULTS: The presence of clinical warning signs or red flags and in particular the combination of several red flags increases the probability of a specific cause of low back pain and should be examined using radiological imaging. An uncomplicated low back pain in an otherwise healthy patient does not normally necessitate imaging.

[Inflammatory diseases of the petrous portion of the temporal bone]. / Entzündliche Erkrankungen des Felsenbeins.

CLINICAL/METHODICAL ISSUE: Inflammatory lesions of the petrous portion of the temporal bone are very common and can be followed by cerebral complications. PRACTICAL RECOMMENDATIONS: Thin layer computed tomography (CT) is useful for detecting bony changes of the temporal bone and contrast-enhanced magnetic resonance imaging (CE MRI) is a sensitive method for detecting cerebral complications.

Risk factors associated with poor lymph node harvest after colon cancer surgery in a national cohort.

AIM: Evaluation of ≥ 12 lymph nodes (LNs) is recommended after surgery for colon cancer. A harvest of ≤ 8 is considered poor, but few reports have evaluated risk factors associated with a poor harvest. This aims of this study were to analyse the clinical, surgical and pathological factors associated with poor LN harvest (LNH), the total number of examined nodes and the effect of LN number on stage. METHOD: All patients reported to the Norwegian Colorectal Cancer Registry during 2007 and 2008 who underwent curative resection for Stage I-III colon cancer were studied. Risk factors for poor LNH and the proportion of Stage III disease were analysed by univariate and multivariate analyses. RESULTS: A total of 2879 patients were included in the study. The median LNH was 14. Overall, 69.9% had ≥ 12 lymph nodes and 14.4% had ≤ 8 LN (poor harvest). Multivariate analysis showed that male sex, age > 75 years, sigmoid tumours, pT category 1-2, failure to use the pathology report template and distance of ≤ 5 cm from the bowel resection margin were all independent factors for poor LNH. Age < 65 years, pT category 3-4, and poor tumour differentiation were independent predictors of Stage III disease. An increased LNH did not increase the proportion of patients identified as being LN positive at the ≤ 8, 9-11 and ≥ 12 LN levels. CONCLUSION: Adequate LNH was achieved in the majority of curative colon cancer resections in this national cohort. Elderly, male patients with sigmoid cancers, and a short distal margin were at increased risk of a poor LNH.

[Von Hippel-Lindau syndrome]. / Von-Hippel-Lindau-Syndrom.

Von Hippel-Lindau syndrome is an autosomal dominant inherited phacomatosis with a predisposition for the central nervous system and retina. There is variable expression with hemangioblastomas in the brain, medulla oblongata, spinal chord, renal carcinoma, pheochromocytoma, pancreatic cysts and islet cell tumors as well as tumors of the endolymphatic sac of the inner ear. Clinical symptoms occur first after an age of approximately 30 years. Magnetic resonance imaging (MRI) of the neuroaxis is indicated in all patients with a suspicion of von Hippel-Lindau syndrome.

[First occurrence of an organic manic schizophreniform syndrome followed by catatonia induced by anti-NMDA-receptor encephalitis]. / Erstmanifestation eines organischen manisch-schizophreniformen Syndroms mit nachfolgender Katatonie bei NMDA-Rezeptor-Antikörper-positiver Encephalitis.

We report on a 39-year-old female patient who developed catatonia after there had been schizomanic symptoms in the six months before. At admission the patient exhibited catatonia, a tetraspastic syndrome and focal epileptic seizures. The cranial MRI revealed bilateral subcortical hyperintense lesions which took up contrast agent. Examination of the cerebrospinal fluid disclosed a lymphocytic pleocytosis and autochthone oligoclonal bands. In the serum autoantibodies against the NMDA-NR-1 receptor were reproducibly detected. A detailed search for a tumour was negative. In detail, we could exclude a neoplasm of the ovaries which is often present in the paraneoplastic type of anti-NMDA-receptor encephalitis. Therefore we assume an autoimmune, not paraneoplastic, encephalitis in our patient. The symptoms improved significantly after an immunosuppressive therapy - initially with glucocorticoids followed by rituximab - had been initiated. This case illustrates that an autoimmune encephalitis should be looked for when first psychotic symptoms occur.

Treatment with 4Jointz reduces knee pain over 12 weeks of treatment in patients with clinical knee osteoarthritis: a randomised controlled trial.

OBJECTIVE: To assess the efficacy of thrice daily topical 4Jointz utilizing Acteev technology (a combination of a standardized comfrey extract and a pharmaceutical grade tannic acid, 3.5 g/day) on osteoarthritic knee pain, markers of inflammation and cartilage breakdown over 12 weeks. PATIENTS AND METHODS: Adults aged 50-80 years (n = 133) with clinical knee OA were randomised to receive 4Jointz or placebo in addition to existing medications. Pain and function were measured using a visual analogue scale (VAS) and the Knee Injury and Osteoarthritis Outcome Score (KOOS) scale at baseline, 4, 8 and 12 weeks. Inflammation was measured analysing IL-6 expression and CTX-2 presence as representative for cartilage breakdown using ELISA, at baseline and 12 weeks. RESULTS: Pain scores significantly reduced in the group who received 4Jointz compared to the group who received placebo after 12 weeks using both the VAS (-9.9 mm, P = 0.034) and the KOOS pain scale (+5.7, P = 0.047). Changes in IL-6 and CTX-2 were not significant (-0.04, P = 0.5; -0.01, P = 0.68). Post-hoc analyses suggested that treatment may be most effective in women (VAS -16.8 mm, P = 0.008) and those with milder radiographic osteoarthritis (OA) (VAS -16.1 mm, P = 0.009). Rates of adverse events were similar in both groups, excepting local rash that was more common amongst participants receiving 4Jointz (21% vs 1.6%, IRR 13.2, P = 0.013), but only 26% (n = 4) of participants with rashes discontinued treatment. There were no changes in systemic blood results. CONCLUSIONS: Topical treatment using 4Jointz reduced pain but had no effect on inflammation or cartilage breakdown over 12 weeks of treatment. TRIAL REGISTRATION: Australia and New Zealand Clinical Trials registry ACTRN12610000877088.

Natural distribution and co-infection patterns of microsporidia parasites in the Daphnia longispina complex.

Microsporidia are intracellular parasites, frequently infecting the planktonic crustacean Daphnia. Questioning the ability to detect and identify microsporidia with conventional microscopic techniques, we applied molecular methods in order to investigate the distribution and co-infection patterns of this parasite among 8 communities of the Daphnia longispina hybrid complex. Eight microsporidian taxa were detected, including 3 that previously had not been characterized genetically. Microsporidian communities from nearby lakes were found to be more similar to each other, apparently due to short distance dispersal via secondary hosts. Moreover, we detected seasonal (but not interannual) changes in microsporidian community structure. With some microsporidia being host-specific, these changes might have resulted from seasonal changes in host taxon and clonal composition. The 2 dominant and closely related parasite species were found mainly in single infections, whereas another pair of related microsporidians was found predominantly in co-infections; suggesting species-level differences in the ability to colonize infected hosts. By applying molecular methods, we were not only able to unambiguously identify parasite taxa but also to reveal multiple infections that otherwise would have remained undetected. Given the increased level of accuracy and sensitivity, we highly recommend molecular approaches in future parasite surveys of Daphnia infections.

Adherence to national guidelines for surveillance after curative resection of nonmetastatic colon and rectum cancer: a survey among Norwegian gastrointestinal surgeons.

AIM: National guidelines recommend enrollment of patients in surveillance programmes following curative resection of colorectal carcinoma (CRC) in order to detect recurrence or distant metastasis at an asymptomatic/early stage when secondary curative treatment can be offered. Little is known about surgeons' adherence to such guidelines. In this national survey we analyse adherence and attitudes to postoperative follow up among Norwegian gastrointestinal surgeons involved in the care of patients with CRC. METHOD: We performed a nationwide survey of all hospitals performing surgery for colon and/or rectum cancer. The presence of a surveillance programme, the type of programme, adherence to national guidelines or report on any deviation thereof, location of follow up at the hospital or with a general practitioner (GPs) and the estimated annual volume of surgery were queried through mail and telephone. RESULTS: All hospitals (n=41) performing colorectal surgery responded, of which 25 (61%) conducted postoperative follow up by surgeons in the hospital outpatient clinics, four (10%) carried out follow up with a combination of hospital outpatient visits and visits to GPs, and 12 (29%) referred surveillance to the GP alone. For total reported patient numbers, almost two-thirds (60%) received surveillance according to national recommendations through outpatient visits with the surgeon or GP, while one-third (37%) were subject to other alternative routines. A small number (2%) received informal 'ad hoc' surveillance only. More liberal use of imaging outside guideline recommendations was reported for rectal cancer patients, while colon cancer patients treated in larger hospitals were more likely to be referred for GP surveillance. CONCLUSION: All hospitals reported having a strategy for surveillance after surgery for colon and rectal cancer, but there was considerable variance in strategy. A scientific audit of the true level of compliance, effectiveness and cost-benefit is warranted at a national level.