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In penile squamous cell carcinoma (PSCC), the outcome largely depends on early detection and resection of inguinal lymph node metastases. We investigated the role of metastasis suppressor protein kang ai 1 (KAI1)/cluster of differentiation 82 (CD82), which is known to be of prognostic significance for a wide variety of cancers. Moreover, we analysed the tumours for human papillomavirus (HPV) DNA and loss of heterozygosity at the 11p11.2 locus. Tissue samples of 30 primary PSCCs were investigated immunohistochemically using an anti-KAI1/CD82 polyclonal antibody. The expression was assessed according to the degree of KAI1/CD82-positive tumour cells as positive, decreased or negative. The presence of HPV6/11, HPV16 and HPV18 DNA was analysed by polymerase chain reaction. All patients with decreased or negative expression of KAI1/CD82 in primary lesions had lymph node metastases (p = 0.0002). Patients with positive KAI1/CD82 expression showed a significant better prognosis for survival compared to the other groups (p = 0.0042). Presence of HPV DNA was associated with decreased or negative KAI1/CD82 expression. Lacking or decreased expression of metastasis suppressor gene KAI1/CD82 appears to be a prognostic parameter for the occurrence of lymph node metastases in PSCC. Our study suggests an association of decreased KAI1/CD82 expression with tumour progression, development of metastases and disease-specific death. [ABSTRACT FROM AUTHOR]

Intranodal palisaded myofibroblastoma (IPM) is a rare benign spindle-cell tumor of lymph nodes with myofibroblastic/ smooth muscle differentiation. We present another case of IPM that confirms the myofibroblastic differentiation of the tumor cells and identifies the so-called amianthoid fibers as collagen deposits by immunohistochemical and ultrastructural techniques. Because IPM shares histomorphologic characteristics with an inflammatory myofibroblastic tumor that has been associated with a virus-induced alteration of cell cycle regulation, the diagnostic approach was extended in this case. We were able to demonstrate cyclin D1 overexpression but could detect neither amplification of the CCND1 gene nor allelic loss at chromosomes 9p22-21 and 13q (surrounding the genes p16 and Rb, respectively). Furthermore, no evidence of human herpesvirus-8 or Epstein-Barr virus infection could be found by polymerase chain reaction or immunostaining. Nevertheless, our results point to the cell cycle regulatory genes as a factor in the pathogenesis of IPM. [ABSTRACT FROM AUTHOR]

Background: Visual impairment (VI) due to neoplastic infiltration of the optic canal (OC) is frequently seen in skull base meningiomas representing a significant restriction in patients` quality of life. However, the delicate anatomy of this region often prevents gross total tumor resection. The aim of the present study was to evaluate the impact of intradural OC decompression and postoperative oncological procedure on preservation of visual acuity in subtotal resected skull base meningiomas., Methods: A retrospective analysis of 31 consecutive patients (19 females, 12 males; mean age 53 [range 18-78]), treated in our institution between 01/2011- 09/2014 was performed. Patients` charts were analyzed with special respect to operative procedure, postoperative treatment and procedural impact on late visual function., Results: Most patients (74.2%) had VI prior to surgery. A pterional craniotomy (97%) facilitated subtotal tumor removal in 71% of the patients with no intraoperative and a low rate (6.4%) of postoperative complications. Adjunctive radiotherapy was performed in 19.3% of the patients. Preoperative visual acuity was preserved or improved in 92% of the patients. Substantial tumor regrowth occurred in only 11.2% of the patients., Conclusions: Intradural decompression of the OC stabilizes visual function in subtotally resected skull base meningiomas. Moreover, adjuvant radiotherapy seems to further benefit visual outcome which has to be evaluated in further prospective studies.

Introduction: Because individuals with serrated polyps and adenomas are at increased risk of developing new polyps and colorectal cancer (CRC), surveillance after resection is justified. After adenoma resection, most international guidelines are consistent, but recommendations for surveillance after serrated polyp resection vary. The United States Multi-Society Taskforce on CRC (US-MSTF) base surveillance intervals on serrated polyp subtype (traditional serrated adenoma, sessile serrated polyp, hyperplastic polyps), while the European Society of Gastrointestinal Endoscopy (ESGE) guidelines do not take serrated polyp subtype into account. We evaluated the implications of this difference in a primary colonoscopy screening cohort., Methods: We included participants from a large colonoscopy screening trial. In a post-hoc simulation, assuming full protocol adherence, we determined the surveillance interval for each subject based on their polyp burden, using the most recent US-MSTF and ESGE guidelines., Results: We included 5323 participants, of whom 1228 had one or more serrated polyps. In 5201 of all participants (98 %; Cohen's kappa 0.90) and in 1106 of those with serrated polyps (90 %; Cohen's kappa 0.80), both guidelines recommended identical surveillance intervals. Recommendations for a 3-year surveillance interval were identical between the two guidelines. All 122 subjects with discordant recommendations would receive a follow-up colonoscopy after 10 years using ESGE guidance and after 5 years using US-MSTF guidance., Conclusion: Despite the different criteria used to determine surveillance after serrated polyp resection, most individuals are recommended identical colonoscopy surveillance intervals whether following the ESGE or US-MSTF guidelines. This suggests that surveillance recommendations do not need to consider the serrated polyp subtype., Competing Interests: None, (© Georg Thieme Verlag KG Stuttgart · New York.)

Background: Cushing's disease (CD) and Cushing's syndrome (CS) are chronic illnesses, characterized by symptoms of prolonged hypercortisolism, which often changes to hypocortisolism after successful treatment. In view of the high disease burden of CD/CS patients and long-term impaired quality of life, the present survey was conducted to gain information about subjective illness distress and patients' specific needs in terms of supportive measures beyond medical interventions., Patients and Methods: Cross-sectional questionnaire study including patients with CD treated in 2 German neurosurgical tertiary referral centers and CD/CS patient members of a US-based patient support group completed a survey inquiring about disease burden, coping strategies, and support needs. Additionally, the degree of interest in different offers, e.g., internet-based programs and seminars, was assessed., Results: 84 US and 71 German patients answered the questionnaire. Patients in both countries indicated to suffer from Cushing-related symptoms, reduced performance, and psychological problems. 48.8% US patients and 44.4% German patients stated that good medical care and competent doctors helped them the most in coping with the illness. US patients were more interested in support groups ( p = 0.035) and in courses on illness coping ( p = 0.008) than the German patients, who stated to prefer brochures ( p = 0.001). 89.3% of US patients would attend internet-based programs compared to 75.4% of German patients ( p = 0.040). There were no differences between groups for the preferred duration of and the willingness to pay for such a program, but US patients would travel longer distances to attend a support meeting ( p = 0.027)., Conclusion: Patients in both countries need skilled physicians and long-term medical care in dealing with the effects of CD/CS, whereas other support needs differ between patients of both countries. The latter implies that not only disease-specific but also culture-specific training programs would need to be considered to satisfy the needs of patients in different countries.

Purpose: Oro-dental pathologies (ODP) such as enlargement of the tongue, mandibular prognathism, and spaced teeth are characteristic features of acromegaly. Their frequency of occurrence during the course of the disease is largely unresolved. Purpose of this study was to assess ODP and oro-dental treatments in patients with acromegaly with regard to the length of the diagnostic process, tumor histology, and quality of life (QoL)., Methods: Single-center retrospective survey study using questionnaires on dental symptoms, diagnostic process, and treatment in patients with acromegaly operated on a growth hormone-secreting pituitary adenoma. The association between ODP and QoL was assessed using the Short-Form 36 (SF-36) Health Survey., Results: 145/314 patients completed the questionnaires. 80.7% were affected by any ODP, most frequently enlargement of the tongue (57.9%), spaced teeth (42.8%), mandibular growth (24.1%), and mandibular prognathism (22.1%). ODP were significantly more frequent in patients with sparsely vs. densely granulated adenomas (p = 0.045). Early diagnosis within 2 years was associated with significantly fewer ODP than later diagnosis (68.5 vs. 87.2%, p = 0.009). Treatments included dental crowns (16.6%), dental bridges (12.4%), dental implants (9.7%), dental prostheses (3.4%), orthodontal (i.e., braces, 6.9%), and surgical correction of the teeth (2.1%). Physical QoL was significantly lower in patients with ODP than in those without (p = 0.014)., Conclusion: In our large series of patients, four of five patients were affected by ODP at any time during the course of the disease. The results highlight the importance of early identification and treatment of oro-dental problems in patients with acromegaly as hallmarks of the disease.

Aims: In the near future, an immunoscore based on the quantification of lymphocytic populations can be expected as a fundamental supplement of colorectal cancer (CRC) classification. This study explored whether latent viral infection has an influence on prognostically relevant host immunity in CRC., Methods and Results: CD8 + lymphocytic infiltration in three tumour compartments of 121 CRC was compared with clinical data and occurrence of latent infection with herpes simplex virus (HSV1, HSV2), cytomegalovirus (CMV), human papillomavirus (HPV16 and HPV18) in the tumour tissue, which was determined by polymerase chain reaction (PCR). Intraepithelial CD8 + lymphocytic infiltration (IE CD 8+ ) showed a trend towards correlation with clinical stage (P = 0.073), significant differences between CRC with and without metastases (P = 0.001) and a significant correlation with overall survival (OS, P = 0.001). Each of these three clinical parameters showed a significant link to IE CD 8+ in the virus DNA-negative (P-values: 0.001-0.036), but no significant differences in the virus DNA-positive subgroup, which is consistent with a moderating effect of virus DNA on these associations. A significant correlation of CD8 + infiltration in the invasive margin (IM CD 8+ ) with OS (P = 0.016) was also moderated by virus DNA., Conclusion: Our data suggest a possible influence of latent viral infection on the association between clinical outcome and CD8 + lymphocytic infiltration in CRC tissue. After confirmation of these results by large cohort studies, a potential interaction between microbial pathogens and host immunity in CRC and its impact on prognostic immunoscores and/or new therapeutic strategies should be investigated further., (© 2017 John Wiley & Sons Ltd.)

Objective: Thunderclap headache and visual disturbances are typical clinical features of pituitary apoplexy (PA). Because of the acute symptomatology, many patients are referred to a neurosurgical department without prior endocrinological assessment. It is the aim of the present study to analyze initial presenting symptoms, outcome and associated endocrine disturbances in a cohort of patients with pituitary apoplexy primarily seen by neurosurgeons., Patients and Methods: Retrospective single-center study in a neurosurgical department. Patients' records were reviewed for clinical, neuropathological and endocrinological findings. The diagnosis of PA was based on clinical, imaging and histological findings., Results: A total of 60 patients were studied. They were referred most often by neurologists (n=16), and family physicians (n=12). Only 2 patients received an endocrinological work-up prior to admission. The most frequently documented presenting symptoms were headache (n=54), visual field defects (n=13), reduction of visual acuity (n=17) and/or diplopia (n=19). An endocrinological history had rarely been taken and hormone blood tests were oftentimes incomplete or not ordered. At 3-month follow-up 18/44 patients had complete anterior hypopituitarism. At 12 months, 21/60 patients were lost to endocrinological follow-up., Conclusions: The classic neurological symptoms of PA were well documented in our patient cohort, whereas endocrinological symptoms, especially those indicative of pituitary dysfunction were underreported. Neurologists and neurosurgeons need to be aware of the endocrinological sequelae of pituitary apoplexy in order to avoid potentially lethal complications. Patients should be counselled to adhere to long-term endocrinological and neurosurgical follow-up., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Increased physical activity may be advantageous for weight loss., Objective: We investigated the effects of an energy-restricted diet with and without moderate walking on body weight, body composition, resting energy expenditure (REE), and endocrine and cardiometabolic risk variables in overweight and obese participants., Methods: A 12-wk, randomized, 2-arm, parallel, controlled, energy-restricted (500-800 kcal/d) dietary intervention study was conducted in 82 men and women [mean baseline characteristics: age, 39.4 y; weight, 99.3 kg; body mass index (in kg/m2), 31.9]. Participants were divided into 2 groups. One group received a hypoenergetic diet (DI) only (n = 44). The second group received the same DI and participated in a regular walking program of 2.5 h/wk (DI + walking; n = 38)., Results: After the 12-wk intervention, body weight was significantly decreased in the DI + walking group and the DI group (-8.8 compared with -7.0 kg, P = 0.064 for intergroup differences). The decrease in body weight was accompanied by a significant reduction in total fat mass, which was significantly more pronounced in the DI + walking group than in the DI group (-6.4 ± 3.1 compared with -4.8 ± 3.0 kg; P = 0.020). REE after 12 wk was not significantly different compared with the baseline REE. Diastolic blood pressure, mean arterial pressure, LDL cholesterol, and non-HDL cholesterol were similarly significantly improved by both interventions. In the DI + walking group, insulin and the homeostasis model assessment of insulin resistance index were also significantly reduced. Serum free triiodothyronine was significantly decreased and serum cortisol was significantly increased in both groups., Conclusions: Participation in a 12-wk weight-loss study resulted in significant reductions in body weight and fat mass and was associated with significant improvements in biomarkers for cardiovascular disease risk. Moderate weight loss was not accompanied by a reduction in REE. Additional moderate walking enhanced the effects of a DI on fat loss and serum insulin. This trial was registered at www.germanctr.de/ and http://apps.who.int/trialsearch/ as DRKS00006827., (© 2017 American Society for Nutrition.)

Purpose: Headache is a common presenting feature of patients with pituitary adenomas and other tumors of the sellar region. However, at present, it still is unclear whether the headache is actually caused by the tumor. To explore whether there is a relation, we examined in detail the headache types, their relationship to the underlying pathology, and if the headache responded to neurosurgery in a prospective study design., Methods: One hundred twelve patients with tumors of the sellar region scheduled for neurosurgery in a single center were analyzed for presence and quality of headache before surgery and at least 3 months after surgery. Patients received headache and depression self-rating inventories, presented on a handheld computer (PainDetect ® ). Clinical variables thought to impact on headache were analyzed in conjunction with the inventories., Results: Fifty-nine (53%) patients reported headache in the 3 months prior to neurosurgery, 49 (44%) had headache at the time of filling in the questionnaires. The four patients with pituitary apoplexy described thunderclap headache. In the other patients diverse headache types were encountered, most frequently migraine. Untreated gonadotroph deficiency was significantly associated with absence of headache, while none of the other clinical and morphological variables related to headache. Presence of headache and disability due to headache were not significantly reduced after surgery., Conclusion: Apart from pituitary apoplexy we detected no specific headache type in our patient group and no significant improvement of headache after neurosurgery. Headache alone constitutes neither a valid diagnostic marker for the presence of tumors of the sellar region nor a sufficient indication for tumor removal.

This study attempts to determine whether primary tumor tissue could reliably represent metastatic colorectal cancer in therapy-guiding analysis of mitochondrial microsatellite instability. Therefore, we investigated the concordance of microsatellite instability in D310, D514, and D16184 (mitochondrial DNA displacement loop), and its association with selected clinical categories and KRAS/NRAS/BRAF/PIK3CA/TP53 mutation status between primary and metastatic colorectal cancer tissue from 119 patients. Displacement loop microsatellite instability was significantly more frequently seen in lymph node metastases (53.1%) compared to primary tumors (37.5%) and distant metastases (21.4%) ( p = 0.0183 and p = 0.0005). The discordant rate was significantly higher in lymph node metastases/primary tumor pairs (74.6%) than in distant metastases/primary tumor pairs (52.4%) or lymph node metastases/distant metastases pairs (51.6%) ( p = 0.0113 and p = 0.0261) with more gain (86.7%) than loss (61.1%) of microsatellite instability in the discordant lymph node metastases ( p = 0.0024). Displacement loop instability occurred significantly more frequently in lymph node metastases and distant metastases of patients with early colorectal cancer onset age <60 years ( p = 0.0122 and p = 0.0129), was found with a significant high rate in a small cohort of TP53-mutated distant metastases ( p = 0.0418), and was associated with TP53 wild-type status of primary tumors ( p = 0.0009), but did not correlate with KRAS, NRAS, BRAF, or PIK3CA mutations. In conclusion, mitochondrial microsatellite instability and its association with selected clinical and molecular markers are discordant in primary and metastatic colorectal cancer, which could have importance for surveillance and therapeutic strategies.

The aim of this cross sectional anatomical study is to determine the distribution of the defined anatomical variations of the Sylvian fissure (SF) in a normal population and to analyze its bilateral superposable presentation. Furthermore, we examined the course of the middle cerebral artery (MCA) and the division of the MCA branches in relation to the SF types. A total of 300 cranial CT scans - 100 CT angiography datasets and 86 MRIs of patients without intracranial pathologies - were reviewed. The SF was categorized in five types based on Yasargils description and our previous publication. The length, diameter and branches of the MCA were measured and compared to the SF types. SPSS 23.0 for Windows® was used for statistical analysis. We analyzed data of 300 patients (171 male, 129 female; mean age 51.6years). Symmetric and mirror-imaged coherence of the SF was found in 266 patients (88.7%, χ 2 (8)=3.04, p=0.932). The distribution of the SF types showed significant differences in patients younger than 60 years compared to older patients. A bifurcation was observed in 72.0%. A trifurcation was observed in 12.0% and a false bifurcation in 16.0% of patients. There was no significant difference of the measured diameters or length of the M1 segments according to the SF types. In this CT and MRI based anatomical study we could show that a twisted and narrow SF occurred more frequently in patients younger than 60 years of age. The SF has a high congruence intra-individually. The anatomical condition might influence the size and configuration of the proximal MCA, which in turn might influence the surgeon's choice of the approach to the SF. Preoperative evaluation on the basis of the presented data, may help to decide for an appropriate approach to the SF., Competing Interests: Conflict of interest: the authors declare no potential conflict of interest.

Objective: Even if treated, acromegaly has a considerable impact on patient quality of life (QoL); despite this, the exact clinical determinants of QoL in acromegaly are unknown. This study retrospectively examines a cohort of treated patients with acromegaly, with the aim of identifying these determinants., Methods: Retrospective survey analysis, with 165 patients included in the study. All patients completed a survey, which included demographic data and the clinical details of their disease, the Short Form-36 Health Survey (SF-36), the revised Beck Depression Inventory (BDI-II), and the Bern Embitterment Inventory (BEI). Stepwise regression was used to identify predictors of QoL., Results: The strongest predictors of the physical component score of the SF-36 were (in order of declining strength of association): Delay between first presentation of the disease and diagnosis, body mass index (BMI), number of doctors visited before the diagnosis of acromegaly, and age at diagnosis. For the mental component score, the strongest predictors were: number of doctors visited, previous radiotherapy, and age at study entry; and, for the BDI-II score: number of doctors visited, previous radiotherapy, age at study entry, and employment status at the time of diagnosis. The following were predictors of the BEI score: number of doctors visited, and age at study entry., Conclusion: Diagnostic delay and lack of diagnostic acumen in medical care provision are strong predictors of poor QoL in patients with acromegaly. Other identified parameters are radiotherapy, age, BMI, and employment status. An efficient acromegaly service should address these aspects when devising disease management plans., Abbreviations: BDI-II = Beck Depression Inventory II BEI = Bern Embitterment Inventory BMI = body mass index IGF-1 = insulin-like growth factor 1 MCS = mental component summary (score) PCS = physical component summary (score) QoL = quality of life SDS = standard deviation score SF-36 = Short Form-36 Health Survey.

The endoscopic transnasal route for the surgical removal of tumors in the sellar region is frequently associated with nasal complications such as synechiae or impaired nasal breathing. In this study, we investigated the impact of septal splints on avoiding surgery-related co-morbidities. 49 patients in whom endoscopic transnasal, transsphenoidal surgery for sellar tumors was performed between 2012 and 2014 were studied. In 30 of these, nasal septal splints were applied at the end of surgery to both sides of the septum and left in situ for 10 days (group 1), 19 patients received no splints (group 2). A standardized postsurgical follow-up investigation with endoscopic nasal examination, rhinomanometry and olfactory testing was performed on average 2 months postoperatively. Patients' subjective nose-related discomfort at follow-up was assessed descriptively using a set of standardized self-rating statements on nasal problems. Synechias occurred less likely with nasal septal splints (n = 15; 50 %) than without (n = 16; 84.2 %). Moreover, multiple synechiae were predominantly observed in the group without septal splints (n = 10 vs. n = 2). Rhinomanometry showed improved flow-V150-inspiration scores when splints were used (with significant differences between groups for the left nostril: p = 0.039 and p = 0.022, resp.). In accordance, impaired nasal breathing after surgery was reported more frequently by 76.9 % of patients without splints, but only 56 % of patients with splints. Our results provide support for the application of nasal septal splints when operating endoscopically on tumors in the sellar region to reduce postoperative synechias and to improve nasal breathing.

Purpose: Quality of life (QoL) and psychosocial well-being are substantially impaired in patients with Cushing's disease (CD), not only at the acute illness stage but also after therapy; however, the reason for these impairments remains unclear., Methods: In this cross-sectional, patient-reported outcome study, we conducted a postal survey on psychosocial impairment and coping strategies in patients after surgical treatment of CD in three large tertiary referral centers. In total, 176 patients with CD completed a compilation of self-assessment inventories pertaining to depression (Hospital Anxiety and Depression Scale, HADS), QoL (Short Form SF-36, Tuebingen CD; Tuebingen CD-25), coping style (Freiburg questionnaire on coping with illness, FKV-LIS), and embitterment (Bern Embitterment Inventory), on average 6.8 ± 6.66 years after surgery. Regression analyses were performed to identify predictors of psychosocial impairment., Results: At the time of the study, 21.8 % of patients suffered from anxiety, 18.7 % experienced an above-average feeling of embitterment, and 13.1 % suffered from depression. Maladaptive coping styles (FKV-LIS subscales depressive coping and minimizing importance) emerged as robust and strong predictors of psychosocial impairment in all inventories; while age, sex, and hydrocortisone intake failed to explain the variance in these measures., Conclusion: Similar to several studies in non-pituitary patient cohorts (e.g., patients with multiple sclerosis or lower back pain), our results indicate that psychosocial impairment in CD is significantly influenced by how the patient deals with the illness. Therefore, psychological training of positive coping styles could be a helpful complementary therapy in the overall treatment strategy of CD.

Purpose: Early diagnosis is a success factor for the prevention of long-term comorbidity and premature death in patients with acromegaly, but large-scale data on the diagnostic process and disease management are scarce. Therefore, we aimed to evaluate the diagnostic process, implementation of treatment and changes in life situation in patients with acromegaly, focusing on sex-specific differences., Methods: Non-interventional patient-reported outcome study. 165 patients with clinically and biochemically proven acromegaly were questioned about the diagnostic process and utilization of health care by means of a self-developed standardized postal survey including questions on acromegaly symptoms experienced before diagnosis, number and specialty of consulted doctors, time to diagnosis and aftercare., Results: The diagnostic process took 2.9 (SD 4.53) years, during which 3.4 (SD 2.99) physicians were consulted. Women waited longer [4.1 (SD 5.53) years] than men [1.6 (SD 2.69) years; p = 0.001] for the correct diagnosis, and consulted more doctors in the process [4.0 (SD 2.99) vs. 2.7 (SD 2.84) doctors, p < 0.001, respectively]. In 48.5 % of patients, acromegaly was diagnosed by an endocrinologist (men: 45.1 %; women: 52.4 %). Overall disease duration from symptom onset until last surgery was 5.5 (SD 6.85) years, with no sex differences. A change in employment status was the most commonly reported event after diagnosis and a quarter of the patients stated that the illness had changed their lives., Conclusions: Our findings confirm the urgent need to increase awareness of the clinical manifestation of acromegaly to facilitate an earlier diagnosis of the disease and to provide diagnostic equality across the sexes.

Aims: Failure and side effects of combined cytotoxic therapy are challenges in the treatment of metastatic colorectal cancer (CRC). DPYD gene variations can potentially predict toxicity to 5-fluorouracil (FU)-based therapy and KRAS-, NRAS-, BRAF-, PIK3CA-wild type status is a known prerequisite for epidermal growth factor receptor (EGFR) inhibitor therapy. This study was performed to search for a possible link between these therapeutic markers., Methods: The DPYD gene variations c.496A>G, c.1679T>G, c.2846A>T and KRAS/NRAS/BRAF/PIK3CA mutational status were determined in non-neoplastic, primary CRC and metastatic CRC tissue from 115 patients., Results: The polymorphism c.496A>G was the DPYD gene variant with the highest detection rate (12.9%), occurred predominantly in females (86.7%, p=0.0044) and was exclusively seen in KRAS wild type primary CRC (15/65 (23.1%) vs 0/51 (0%) in KRAS-mutated primary CRC, respectively, p=0.0001)., Conclusions: This genetic profile could define a patient group requiring alternative combined therapeutic approaches. Global testing of large patient cohorts is necessary to prove this concept., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Neuroendocrine differentiation in sporadic colorectal cancer has been recognized since decades, but its clinical impact is still controversially discussed. Detailed parameter analyses hint at the possibility that probably not neuroendocrine differentiation itself, but its association with poor grade of tumor differentiation, lymph node metastases, distant metastases and other unfavorable features contribute to worse clinical outcome. However, other studies deny a relationship between neuroendocrine differentiation and prognosis of colorectal cancer. This review elucidates, whether new insights into the origin of neuroendocrine differentiation in the intestinal epithelium, its regulation by mTOR pathway components and its possible link to the intestinal stem cell compartment could determine a role of neuroendocrine cells as prognostic marker and putative therapeutic target in sporadic colorectal cancer.

Spinal dural arteriovenous fistulas (SDAVFs) are rare pathologies with a yearly incidence of 5-10 new cases/million, constituting 60-80 % of spinal arteriovenous malformations. Clinical symptoms include progressive paraparesis, paresthesias, bladder, and bowel disturbances. The pathophysiology of SDAVFs is not well elucidated. Microneurosurgery and endovascular techniques are established treatment modalities for permanent fistula occlusion, which are oftentimes accompanied by an amelioration of neurological deficits in the long run. Here, we report our interdisciplinary neurosurgical/neuroradiological management strategy of SDAVFs in 32 patients who were evaluated retrospectively. We focused on clinical presentation, microneurosurgical and interventional technique, early, and late neurological results. Quality of life (QoL) was additionally assessed in 12 patients at last follow-up. We discuss the results against the background of the current literature. Our series and the literature indicate that clinical outcome after treatment of SDAVF is favorable in general. Both neurosurgical and neurointerventional therapies appear to be safe and effective, but short-term neurological deterioration after the intervention constitutes an as-of-yet unsolved problem. Beyond age and preoperative neurological state, presence of comorbidities had a significant influence on neurological outcome in our study sample. Self-assessed physical and mental QoL at long-term follow-up was reduced in quite a number of patients and was associated with a poorer neurological result as well as presence of comorbidities. The patients' perspective in terms of QoL was first investigated in this study, but further research on QoL and psychosocial impairment of SDAVF patients is needed to enable individualized counseling and rehabilitation strategies.

Background and Study Aims: Compared with air insufflation, water exchange and carbon dioxide (CO2) insufflation have been shown to reduce colonoscopy discomfort; however, head-to-head studies of the two methods are lacking. We aimed to compare water exchange and CO2 insufflation directly with regard to pain during primary unsedated colonoscopy., Methods: Patients willing to undergo unsedated colonoscopy at three centers in Norway and Poland were randomized 1:1 to water exchange or CO2 insufflation during colonoscope insertion. Patients were blinded to group allocation. The primary end point was the proportion of patients reporting moderate or severe procedural pain on a 4-point verbal rating scale (VRS-4) at discharge. Secondary outcomes included the proportion of patients reporting no pain on the VRS-4., Results: A total of 473 patients were randomized. A discharge pain questionnaire was completed by 226 of 234 patients (97 %) in the water exchange group versus 226 of 239 patients (95 %) in the CO2 group (P = 0.37). Moderate or severe pain was reported by 47 of 226 patients (21 %) in the water exchange group versus 60 of 226 patients (27 %) in the CO2 group (P = 0.15). No pain was reported by 100 of 226 patients (44 %) and 69 of 226 patients (31 %) in the water exchange and CO2 groups, respectively (P = 0.003). On-demand sedation was used in 15 patients (6 %) in each group (P = 0.95)., Conclusions: There was no significant reduction in moderate or severe pain in a comparison of water exchange with CO2 insufflation. The secondary outcome of no pain was significantly more frequent in the water exchange group. Clinical trials registry number: NCT01633333., (© Georg Thieme Verlag KG Stuttgart · New York.)