Biomarker-stratified first-line treatment of right-sided metastatic colon cancer with interdisciplinary collaboration in the IVOPAK II trial.

Patients with right-sided metastatic colon carcinoma have a significantly worse prognosis than those with left-sided colorectal cancer (CRC), regardless of treatment. The aim of the prospective IVOPAK II study was to implement an interdisciplinary guideline-conform personalized CRC palliative therapy of metastatic colorectal carcinoma and to improve the overall survival (OS) by multidisciplinary approach via secondary metastatic resection. We present the efficacy data of first-line treatment and the benefit of interdisciplinary collaboration of right-sided metastatic colon carcinoma patients: n  = 25. RAS mutation: n  = 20 (80%): received systemic first-line treatment: FOLFIRI plus bevacizumab. All-RAS-wildtype: n  = 5 (20%): received systemic first-line treatment: FOLFIRI plus cetuximab. Last date evaluation: 31 January 2024. Median age: 59.6 years (range 42-71), men/women: 14/11. Eastern Cooperative Oncology Group (ECOG) index: 0/1/2 : 11/10/4. Evaluable for response: n  = 25. Complete response: n  = 0, partial response: n  = 14 (56%), stable disease: n  = 8 (32%), progressive disease: n  = 3 (12%), early tumor shrinkage: n  = 13 (52%), estimates progression-free survival: 13 months (95% CI 8-17 months), estimated OS: 48 months (95% CI 25-71 months), median follow-up: 26 months (1-61 months), no evidence of disease: n  = 4 (16%). A chemotherapy doublette regimen with FOLFIRI plus a biological as first-line treatment shows promising efficacy and secondary metastatic resection after interdisciplinary discussion was associated with a survival benefit in right-sided metastatic colon carcinoma.

Additive value of transarterial embolization to systemic sirolimus treatment in kaposiform hemangioendothelioma.

Kaposiform hemangioendothelioma (KHE) is a rare vascular tumor in children, which can be accompanied by life-threatening thrombocytopenia, referred to as Kasabach-Merritt phenomenon (KMP). The mTOR inhibitor sirolimus is emerging as targeted therapy in KHE. As the sirolimus effect on KHE occurs only after several weeks, we aimed to evaluate whether additional transarterial embolization is of benefit for children with KHE and KMP. Seventeen patients with KHE and KMP acquired from 11 hospitals in Germany were retrospectively divided into two cohorts. Children being treated with adjunct transarterial embolization and systemic sirolimus, and those being treated with sirolimus without additional embolization. Bleeding grade as defined by WHO was determined for all patients. Response of the primary tumor at 6 and 12 months assessed by magnetic resonance imaging (MRI), time to response of KMP defined as thrombocyte increase >150 × 103 /µL, as well as rebound rates of both after cessation of sirolimus were compared. N = 8 patients had undergone additive embolization to systemic sirolimus therapy, sirolimus in this group was started after a mean of 6.5 ± 3 days following embolization. N = 9 patients were identified who had received sirolimus without additional embolization. Adjunct embolization induced a more rapid resolution of KMP within a median of 7 days vs 3 months; however, tumor response as well as rebound rates were similar between both groups. Additive embolization may be of value for a more rapid rescue of consumptive coagulopathy in children with KHE and KMP compared to systemic sirolimus only.

Efficacy of catheter-based renal denervation in the absence of antihypertensive medications (SPYRAL HTN-OFF MED Pivotal): a multicentre, randomised, sham-controlled trial.

BACKGROUND: Catheter-based renal denervation has significantly reduced blood pressure in previous studies. Following a positive pilot trial, the SPYRAL HTN-OFF MED (SPYRAL Pivotal) trial was designed to assess the efficacy of renal denervation in the absence of antihypertensive medications. METHODS: In this international, prospective, single-blinded, sham-controlled trial, done at 44 study sites in Australia, Austria, Canada, Germany, Greece, Ireland, Japan, the UK, and the USA, hypertensive patients with office systolic blood pressure of 150 mm Hg to less than 180 mm Hg were randomly assigned 1:1 to either a renal denervation or sham procedure. The primary efficacy endpoint was baseline-adjusted change in 24-h systolic blood pressure and the secondary efficacy endpoint was baseline-adjusted change in office systolic blood pressure from baseline to 3 months after the procedure. We used a Bayesian design with an informative prior, so the primary analysis combines evidence from the pilot and Pivotal trials. The primary efficacy and safety analyses were done in the intention-to-treat population. This trial is registered at ClinicalTrials.gov, NCT02439749. FINDINGS: From June 25, 2015, to Oct 15, 2019, 331 patients were randomly assigned to either renal denervation (n=166) or a sham procedure (n=165). The primary and secondary efficacy endpoints were met, with posterior probability of superiority more than 0·999 for both. The treatment difference between the two groups for 24-h systolic blood pressure was -3·9 mm Hg (Bayesian 95% credible interval -6·2 to -1·6) and for office systolic blood pressure the difference was -6·5 mm Hg (-9·6 to -3·5). No major device-related or procedural-related safety events occurred up to 3 months. INTERPRETATION: SPYRAL Pivotal showed the superiority of catheter-based renal denervation compared with a sham procedure to safely lower blood pressure in the absence of antihypertensive medications. FUNDING: Medtronic.

Blood pressure lowering with alcohol-mediated renal denervation using the Peregrine infusion Catheter is independent of injection site location.

OBJECTIVES: The current analysis utilized core laboratory angiographic data from a prospective, single-arm, open-label, multi-center feasibility study to ascertain whether the location of alcohol infusion within main renal arteries during renal denervation (RDN) had an impact on the BP-lowering effect at 6 months. BACKGROUND: The influence of the location of alcohol infusion during RDN, within the main renal artery (proximal, middle, or distal), on the magnitude of the blood pressure (BP) lowering is unstudied. METHODS: The Peregrine Catheter was used to perform alcohol-mediated RDN with an infusion of 0.6 mL of alcohol per artery as the neurolytic agent in 90 main arteries and four accessory arteries of 45 patients with hypertension. RESULTS: No relationship between the site of alcohol infusion and change from baseline in both office systolic and 24-hour systolic ambulatory BP (ABP) at 6 months was observed. When analyzed at the artery level, the least squares (LS) mean changes ± SEM from baseline to 6 months post-procedure in 24-hour systolic ABP when analyzed by renal arterial location were -11.9 ± 2.4 mmHg (distal), -10 ± 1.6 mmHg (middle), and -10.6 ± 1.3 mmHg (proximal) (all p < 0.0001 for change from baseline within groups). The results were similar for office systolic BP. There was no difference between treated locations (proximal is reference). CONCLUSION: In this post-hoc analysis, the location of alcohol infusion within the main renal artery using the Peregrine system, with alcohol as the neurolytic agent for chemical RDN, did not affect the magnitude of BP changes at 6 months.

Eligibility of Endovascular Repair for Popliteal Artery Aneurysms According the Instructions for Use.

BACKGROUND: Popliteal artery aneurysms (PAAs) are the most common peripheral aneurysms. Although rare and often asymptomatic, there is a significant risk of thrombosis, embolism, and limb loss. The aim of this study was to evaluate the eligibility for endovascular repair of patients treated for symptomatic and asymptomatic PAAs in accordance with the instructions for use (IFU). METHODS: All patients treated for PAA with open surgical repair between the years 2010 and 2017 were analyzed if suitable for endovascular treatment. Preoperative imaging was reviewed for applicability with an interventional radiologist and 2 vascular surgeons. Evaluation was performed in accordance with the following criteria adopted from the IFU of the Gore ® Viabahn stent graft: at least a single-vessel tibial runoff, proximal and distal landing zone more than 2 cm, no large difference in vessel diameter proximal and distal to the aneurysm, no overstenting of significant collaterals necessary, and no inadequate kinking of the artery. The patients were classified in 3 categories: the patient was eligible, endovascular treatment was feasible, and endovascular treatment was not appropriate. RESULTS: 51 patients with 61 symptomatic and asymptomatic PAAs were identified. Forty-five cases were asymptomatic, 11 cases showed clinical symptoms such as claudication, and in 5 cases, the patients presented with acute ischemia. Twenty-four patients were eligible for endovascular intervention, 14 cases were feasible, and in 23 cases, it was not appropriate in accordance with the IFU. CONCLUSIONS: In this study, more than one-third of the patients with PAA were not eligible for endovascular treatment in accordance with the IFU and another 23 % showed substantial reasons against endovascular treatment. These data suggest that endovascular repair remains a treatment option for selected patients only. Cross-sectional imaging is mandatory for procedure selection.

Effects of renal denervation on blood pressure in hypertensive patients with end-stage renal disease: a single centre experience.

BACKGROUND: Sympathetic nerve activity is a hallmark of hypertension in end-stage renal disease (ESRD). An initial proof-of-concept study implies that renal denervation (RDN) is feasible and safe in RDN, but overall data are limited. METHODS: In this single-centre prospective pilot study six patients with ESRD and treatment resistant hypertension were consecutively included. Ambulatory blood pressure (ABP) was measured before and 6 months after RDN (Symplictiy Flex™, Medtronic Inc., Santa Rosa, CA). Moreover, haemodialysis parameters which may affect BP reduction were monitored closely. RESULTS: In all patients bilateral RDN was successful done, without documentation of peri- or postprocedural complications. There was a significant reduction in 24-h ABP by 20 ± 17/15 ± 12 mmHg 6 months after RDN (systolic: 163 ± 16 versus 143 ± 9 mmHg, p = 0.043; diastolic: 96 ± 9 versus 81 ± 15 mmHg, p = 0.043), with similar results for day-, and nighttime values, respectively. Antihypertensive medication was kept stable as well as there was no change in haemodialysis parameters during follow-up. In addition, ultrafiltration/week (1.4 ± 1.4 versus 2.2 ± 1.4 l, p = 0.08) as well as hematocrit (measured at baseline and 6 months after RDN) (33.7 ± 4.3 versus 33.1 ± 3.9%, p = 0.715) revealed no change in volume status. CONCLUSION: Our single-centre pilot study not only supports current data on renal safety of RDN even in small arteries of patients with ESRD, but also enhances the knowledge towards an effective ABP reduction in this type of hypertensive patients.

Catheter-based renal denervation in patients with uncontrolled hypertension in the absence of antihypertensive medications (SPYRAL HTN-OFF MED): a randomised, sham-controlled, proof-of-concept trial.

BACKGROUND: Previous randomised renal denervation studies did not show consistent efficacy in reducing blood pressure. The objective of our study was to evaluate the effect of renal denervation on blood pressure in the absence of antihypertensive medications. METHODS: SPYRAL HTN-OFF MED was a multicentre, international, single-blind, randomised, sham-controlled, proof-of-concept trial. Patients were enrolled at 21 centres in the USA, Europe, Japan, and Australia. Eligible patients were drug-naive or discontinued their antihypertensive medications. Patients with an office systolic blood pressure (SBP) of 150 mm Hg or greater and less than 180 mm Hg, office diastolic blood pressure (DBP) of 90 mm Hg or greater, and a mean 24-h ambulatory SBP of 140 mm Hg or greater and less than 170 mm Hg at second screening underwent renal angiography and were randomly assigned to renal denervation or sham control. Patients, caregivers, and those assessing blood pressure were blinded to randomisation assignments. The primary endpoint, change in 24-h blood pressure at 3 months, was compared between groups. Drug surveillance was done to ensure patient compliance with absence of antihypertensive medication. The primary analysis was done in the intention-to-treat population. Safety events were assessed at 3 months. This study is registered with ClinicalTrials.gov, number NCT02439749. FINDINGS: Between June 25, 2015, and Jan 30, 2017, 353 patients were screened. 80 patients were randomly assigned to renal denervation (n=38) or sham control (n=42) and followed up for 3 months. Office and 24-h ambulatory blood pressure decreased significantly from baseline to 3 months in the renal denervation group: 24-h SBP -5·5 mm Hg (95% CI -9·1 to -2·0; p=0·0031), 24-h DBP -4·8 mm Hg (-7·0 to -2·6; p<0·0001), office SBP -10·0 mm Hg (-15·1 to -4·9; p=0·0004), and office DBP -5·3 mm Hg (-7·8 to -2·7; p=0·0002). No significant changes were seen in the sham-control group: 24-h SBP -0·5 mm Hg (95% CI -3·9 to 2·9; p=0·7644), 24-h DBP -0·4 mm Hg (-2·2 to 1·4; p=0·6448), office SBP -2·3 mm Hg (-6·1 to 1·6; p=0·2381), and office DBP -0·3 mm Hg (-2·9 to 2·2; p=0·8052). The mean difference between the groups favoured renal denervation for 3-month change in both office and 24-h blood pressure from baseline: 24-h SBP -5·0 mm Hg (95% CI -9·9 to -0·2; p=0·0414), 24-h DBP -4·4 mm Hg (-7·2 to -1·6; p=0·0024), office SBP -7·7 mm Hg (-14·0 to -1·5; p=0·0155), and office DBP -4·9 mm Hg (-8·5 to -1·4; p=0·0077). Baseline-adjusted analyses showed similar findings. There were no major adverse events in either group. INTERPRETATION: Results from SPYRAL HTN-OFF MED provide biological proof of principle for the blood-pressure-lowering efficacy of renal denervation. FUNDING: Medtronic.

Repeating of local therapy of distant metastases increases overall survival in patients with synchronous metastasized rectal cancer-a monocentric analysis.

PURPOSE: The aim was to evaluate the outcome of treatment-naive patients with synchronous metastatic rectal cancer after chemotherapy with FOLFOXIRI followed by local therapeutic procedures of all tumor lesions as complete as possible. METHODS: We reviewed data of 30 patients with synchronous distant metastatic rectal cancer who underwent chemotherapy with FOLFOXIRI and subsequent local therapy in our institution. RESULTS: Median follow-up was 28 months (range: 8; 74). Cumulative overall survival (OS) and progression-free survival (PFS) was 93.3, 76.9, 55.6% and 46.2, 29.7, 29.7% after 1, 2, 4 years. Non-response to chemotherapy with FOLFOXIRI was associated with a highly significant decreased OS (p < 0.0001). The consistent use of local ablative procedures led to a statistically significant increase in OS (p < 0.0001), but not in PFS (p = 0.635). Patients with ≤ 4 distant metastases showed a better OS (p = 0.033). CONCLUSIONS: Response to intensified first-line chemotherapy with FOLFOXIRI, treatment of the primary rectal tumor, and repeated thorough local ablative procedures in patients with synchronous metastasized rectal cancer may lead to long-term survival, even in a subset of patients with unresectable disease at initial diagnosis.

[Management of Complications of Pancreatic Anastomoses]. / Komplikationsmanagement der Pankreasanastomose.

BACKGROUND: The pancreatic anastomosis may be the Achilles heel in pancreatic surgery. When a postoperative pancreatic fistula develops, be it mild or severe, in some cases life-threatening, POPF-associated complications can occur. OBJECTIVES: Possibilities for the prophylaxis, diagnosis and therapy of POPF and POPF-associated complications in an interdisciplinary setting. RESULTS: Differentiated diagnostic and therapeutic management of POPF grade A - C is supported by recent studies to reduce morbidity and mortality. Depending on time and severity of POPF and POPF-associated complications, a conservative/interventional or surgical approach is indicated. CONCLUSION: With the precise classification of POPF and POPF-associated complications, interdisciplinary diagnostic and therapeutic management can reduce morbidity and mortality after pancreatic surgery.

Immediate changes of angiosome perfusion during tibial angioplasty.

OBJECTIVE: In recent years, a controversial discussion about the clinical relevance of the angiosome concept during tibial angioplasty has developed. Therefore, we conducted a prospective study to evaluate the angiosome concept on the level of microcirculation during tibial vascular interventions. METHODS: Thirty patients with isolated tibial angioplasty were examined prospectively. Macrocirculation was evaluated by measurement of the ankle-brachial index (ABI). For the assessment of microcirculation, a combined method of laser Doppler flowmetry and tissue spectrometry (O2C; LEA Medizintechnik GmbH, Giessen, Germany) was applied. Microcirculatory parameters were measured continuously during the procedures. Measuring points were located over different angiosomes of the index foot; a control probe was placed on the contralateral leg. RESULTS: Cumulated microcirculation parameters (sO2, flow) as well as the ABI showed a significant improvement postinterventionally (ABI, P < .001; sO2, P < .001; flow, P < .001). Assessment of the separate angiosomes of the index leg and the comparison of the directly revascularized (DR) and indirectly revascularized (IR) angiosomes showed no significant difference concerning the microperfusion postinterventionally (DR - IR: sO2, P = .399; flow, P = .909) as well as during angioplasty. Even a further subdivision of the collective into patients with diabetes (sO2, P = .445; flow, P =.758) and renal insufficiency (sO2, P = .246; flow, P = .691) could not demonstrate a superiority of the direct revascularization at the level of microcirculation in these patients (comparison DR - IR). CONCLUSIONS: There is a significant overall improvement in tissue perfusion of the foot immediately after tibial angioplasty. The effect shown in this study, however, was found to be global and was not restricted to certain borders, such as defined by angiosomes.

Outcomes and Influence of the Pedal Arch in Below-the-Knee Angioplasty in Patients with End-Stage Renal Disease and Critical Limb Ischemia.

BACKGROUND: Management of dialysis patients with critical limb ischemia (CLI) still represents a challenge to vascular medicine, whereas the effects of the pedal arch quality in these patients with predominant affection of the infrapopliteal vessels have rarely been evaluated. Therefore, our aim was to analyze the outcomes of infrapopliteal angioplasty in the setting of chronic renal failure (end-stage renal disease) and evaluate the influence of the pedal arch involvement on clinical success. METHODS: Prospective follow-up of 32 ERSD patients on hemodialysis (mean age, 72 years) with CLI and consecutive infrapopliteal angioplasty over a 5-year period 2010-2014 was performed. Mean follow-up was 10 months (range, 0-51 months). Statistical end points were defined for amputation-free survival, overall survival, and wound healing. Each patient's pedal arch was classified in 4 categories according to patency on completion angiography and the influence of the pedal arch quality on end points was assessed. RESULTS: A total of 44 vessels in 32 ischemic legs were treated. Technical success was achieved in 96% of patients, no major complications were observed. A 30-day mortality rate amounted 6% with no procedure-related deaths. The 1-year amputation-free survival rate was 56% and 34% at 2 years. Two major amputations were required. Subsequent revascularization procedures were necessary in 11 patients (10 redo angioplasty, 1 pedal bypass graft). The pedal arch was classified as category I in 1 patient (3%), category IIa in 12 (38%), IIb in 3 (9%), and III in 16 patients (50%). No statistical significant differences in terms of survival or wound-healing rate were observed between those groups, and the pedal arch quality had no impact on predefined end points. CONCLUSIONS: End-stage renal disease patients represent a subgroup with poor prognosis of limb salvage in CLI. Amputation-free survival remains poor and based on these data, an endovascular therapy is feasible and safe in these highly multimorbid patients. The quality of the pedal arch was not found to have any impact on wound healing or survival in the present study.

Brightness discrimination in the day- and night-adapted wandering spider Cupiennius salei.

Cupiennius salei is a nocturnal spider with eight eyes, which undergo a remarkable circadian cycle: the rhabdomeric membrane of the photoreceptor cells is dismantled during the day and rebuilt at the beginning of the night. Such drastic changes might influence the brightness discrimination ability. We tested this hypothesis by presenting square-shaped flickering stimuli with certain luminances on stationary backgrounds with other luminances to spiders with day- or night-adapted eyes. When the spider, through its three pairs of so-called secondary eyes, perceives a visible contrast between the stimulus and the background, its principal eye muscle activity should increase. We therefore recorded this activity in vivo to assess the brightness discrimination ability of Cupiennius salei. Our results show that this spider has good brightness discrimination ability, which is significantly better with dark-adapted eyes. A Michelson contrast of 0.1 to 0.2 at night, and of 0.2 to 0.3 for day-adapted eyes, is sufficient to elicit a significant response, except below a critical value of luminance (~16 cd m(-2)), where the minimal perceivable contrast needs to be higher. In the Discussion we compare these performances with those of other animals, in particular with jumping spiders.

Successful treatment of a patient with middle aortic syndrome and renovisceral involvement using aorto-aortic bypass: case report and review of recent literature.

Middle aortic syndrome (MAS), defined as localized abdominal or thoracic aortic hypoplasia, represents an extraordinary rare condition, often diagnosed in younger patients with severe renal hypertension. Etiology is divided into congenital and acquired causes (e.g., Takayasu disease). Because of its extremely unfavorable course, treatment of symptomatic patients is mandatory, whereas open surgery with aorto-aortic bypass or patch aortoplasty is considered the standard therapy. This report describes a case of a 19-year-old Macedonian woman presenting with MAS and renal hypertension who was successfully treated with aorto-aortic bypass, including reconstruction of both renal and the hepatic and superior mesenteric arteries, and reviews the current literature.

Skin sodium content as a predictor of blood pressure response to renal denervation.

Patients with treatment resistant hypertension (TRH) are known to have elevated sodium (Na) content in muscle and skin. Renal denervation (RDN) emerged as an adjacent therapeutic option in this group of patients. This analysis aimed at evaluating whether tissue Na content predicts blood pressure (BP) response after RDN in patients with TRH. Radiofrequency-device based RDN was performed in 58 patients with uncontrolled TRH. Office and 24-h ambulatory BP were measured at baseline and after 6 months. To assess tissue Na content Na magnetic resonance imaging (Na-MRI) was performed at baseline prior to RDN. We splitted the study cohort into responders and non-responders based on the median of systolic 24-h ambulatory blood pressure (ABP) reduction after 6 months and evaluated the association between BP response to RDN and tissue Na content in skin and muscle. The study was registered at http://www.clinicaltrials.gov (NCT01687725). Six months after RDN 24-h ABP decreased by -8.6/-4.7 mmHg. BP-Responders were characterized by the following parameters: low tissue sodium content in the skin (p = 0.040), female gender (p = 0.027), intake of aldosterone antagonists (p = 0.032), high baseline 24-h night-time heart rate (p = 0.045) and high LDL cholesterol (p < 0.001). These results remained significant after adjustment for baseline 24-h systolic BP. Similar results were obtained when the median of day-time and night-time ABP reduction after 6 months were used as cut-off criteria for defining BP response to RDN. We conclude that in addition to clinical factors including baseline 24-h ABP Na-MRI may assist to select patients with uncontrolled TRH for RDN treatment.

Blood pressure reduction after renal denervation in patients with or without chronic kidney disease.

Background: Renal denervation (RDN) has emerged as an adjacent option for the treatment of hypertension. This analysis of the Erlanger registry aimed to compare the blood pressure (BP)-lowering effects and safety of RDN in patients with and without chronic kidney disease (CKD). Methods: In this single-center retrospective analysis, 47 patients with and 127 without CKD underwent radiofrequency-, ultrasound- or alcohol-infusion-based RDN. Office and 24-h ambulatory BP and estimated glomerular filtration rate (eGFR) were measured at baseline, and after 6 and 12 months. Results: A total of 174 patients with a mean age of 59.0 ± 10 years were followed up for 12 months. At baseline, mean eGFR was 55.8 ± 21 mL/min/1.73 m2 in patients with CKD and 87.3 ± 13 mL/min/1.73 m2 in patients without CKD. There was no significant eGFR decline in either of the groups during 12 months of follow-up. In patients without CKD, office systolic and diastolic BP were reduced by -15.3 ± 17.5/-7.9 ± 10.8 mmHg 6 months after RDN and by -16.1 ± 18.2/-7.7 ± 9.6 mmHg 12 months after RDN. In patients with CKD, office systolic and diastolic BP were reduced by -10.7 ± 24.0/-5.8 ± 13.2 mmHg 6 months after RDN and by -15.1 ± 24.9/-5.9 ± 12.9 mmHg 12 months after RDN. Accordingly, in patients without CKD, 24-h ambulatory systolic and diastolic BP were reduced by -7.2 ± 15.8/-4.9 ± 8.8 mmHg 6 months after RDN and by -9.0 ± 17.0/-6.2 ± 9.8 mmHg 12 months after RDN. In patients with CKD, 24-h systolic and diastolic BP were reduced by -7.4 ± 12.9/-4.2 ± 9.9 mmHg 6 months after RDN and by -8.0 ± 14.0/-3.6 ± 9.6 mmHg 12 months after RDN. There was no difference in the reduction of office and 24-h ambulatory BP between the two groups at any time point (all P > .2). Similar results have been found for the 6 months data. With exception of rare local adverse events, we did not observe any safety signals. Conclusion: According to our single-center experience, we observed a similar reduction in 24-h, day and night-time ambulatory BP as well as in-office BP in patients with and without CKD at any time point up to 12 months. We conclude that RDN is an effective and safe treatment option for patients with hypertension and CKD.

Characterisation and localisation of the opsin protein repertoire in the brain and retinas of a spider and an onychophoran.

BACKGROUND: Opsins have been found in the majority of animals and their most apparent functions are related to vision and light-guided behaviour. As an increasing number of sequences have become available it has become clear that many opsin-like transcripts are expressed in tissues other than the eyes. Opsins can be divided into three main groups: rhabdomeric opsins (r-opsins), ciliary opsins (c-opsins) and group 4 opsins. In arthropods, the main focus has been on the r-opsins involved in vision. However, with increased sequencing it is becoming clear that arthropods also possess opsins of the c-type, group 4 opsins and the newly discovered arthropsins but the functions of these opsins are unknown in arthropods and data on their localisation is limited or absent. RESULTS: We identified opsins from the spider Cupiennius salei and the onychophoran Euperipatoides kanangrensis and characterised the phylogeny and localisation of these transcripts. We recovered all known visual opsins in C. salei, and in addition found a peropsin, a c-opsin and an opsin resembling Daphnia pulex arthropsin. The peropsin was expressed in all eye types except the anterior median eyes. The arthropsin and the c-opsin were expressed in the central nervous system but not the eyes. In E. kanangrensis we found: a c-opsin; an opsin resembling D. pulex arthropsins; and an r-opsin with high sequence similarity to previously published onychophoran onychopsins. The E. kanangrensis c-opsin and onychopsin were expressed in both the eyes and the brain but the arthropsin only in the brain. CONCLUSION: Our novel finding that opsins of both the ciliary and rhabdomeric type are present in the onychophoran and a spider suggests that these two types of opsins were present in the last common ancestor of the Onychophora and Euarthropoda. The expression of the c-opsin in the eye of an onychophoran indicates that c-opsins may originally have been involved in vision in the arthropod clade. The lack of c-opsin expression in the spider retina suggests that the role for c-opsin in vision was lost in the euarthropods. Our discovery of arthropsin in onychophorans and spiders dates the emergence of arthropsin to the common ancestor of Onychophora and Euarthropoda and their expression in the brain suggests a non-visual function.

The expression pattern of the genes engrailed, pax6, otd and six3 with special respect to head and eye development in Euperipatoides kanangrensis Reid 1996 (Onychophora: Peripatopsidae).

The genes otd/otx, six3, pax6 and engrailed are involved in eye patterning in many animals. Here, we describe the expression pattern of the homologs to otd/otx, six3, pax6 and engrailed in the developing Euperipatoides kanangrensis embryos. Special reference is given to the expression in the protocerebral/ocular region. E. kanangrensis otd is expressed in the posterior part of the protocerebral/ocular segment before, during and after eye invagination. E. kanangrensis otd is also expressed segmentally in the developing ventral nerve cord. The E. kanangrensis six3 is located at the extreme anterior part of the protocerebral/ocular segment and not at the location of the developing eyes. Pax6 is expressed in a broad zone at the posterior part of the protocerebral/ocular segment but only weak expression can be seen at the early onset of eye invagination. In late stages of development, the expression in the eye is upregulated. Pax6 is also expressed in the invaginating hypocerebral organs, thus supporting earlier suggestions that the hypocerebral organs in onychophorans are glands. Pax6 transcripts are also present in the developing ventral nerve cord. The segment polarity gene engrailed is expressed at the dorsal side of the developing eye including only a subset of the cells of the invaginating eye vesicle. We show that engrailed is not expressed in the neuroectoderm of the protocerebral/ocular segment as in the other segments. In addition, we discuss other aspect of otd, six3 and pax6 expression that are relevant to our understanding of evolutionary changes in morphology and function in arthropods.