[DDB2-associated incidence of squamous cell carcinoma in Haflingers: risk minimization by genotyping]. / DDB2-assoziiertes Vorkommen von Plattenepithelkarzinomen beim Haflinger: Risikominimierung durch Genotypisierung.

INTRODUCTION: SCC (squamous cell carinomas) are among the most common eye neoplasms in horses. In recent studies Haflinger horses with a homozygous genotype for a missense variant in the DDB2 gene (damage specific DNA binding protein 2) had a significant increased risk of developing ocular SCC. The aims of this study were to determine the frequency of the SCC-associated risk allele in the DDB2 gene in Swiss and Austrian Haflinger populations and to validate the previously described phenotypic correlation. For this purpose, Haflingers presented at various horse clinics in Switzerland (n = 21, including 11 SCC cases), privately kept Haflingers (n = 52, including 1 SCC case), and Haflingers from a stud farm in the Austrian Tyrol (n = 53) were recruited. The individual DDB2 genotype of the animals was determined using a polymerase chain ceaction (PCR) test using hair follicle or whole blood samples. Of the 12 horses suffering from SCC, nine had ocular SCC and three had non-ocular SCC. Six of the nine Haflingers with ocular SCC and one of the three Haflingers with non-ocular SCC were homozygous for the DDB2 variant. Of the 113 clinically normal animals, 7/113 were homozygous (6 %) and 42/113 were heterozygous (37 %), which corresponds to an allele frequency of 24,8 % in the control cohort. The risk of ocular SCC occurring in Haflingers is significantly increased with the homozygous DDB2 genotype. However, not all animals with SCC carry this gene variant and not all DDB2 homozygous animals develop SCC, which can be explained by the multifactorial genesis of the disease. Due to the high frequency of the undesirable allele, we recommend taking the individual DDB2 genotype of breeding animals into account in order to avoid homozygous offspring with a greatly increased SCC risk by excluding high-risk matings.

INTRODUCTION: Les carcinomes épidermoïdes (CE) sont parmi les néoplasmes oculaires les plus fréquents chez les chevaux. Des études récentes ont montré que les chevaux Haflinger présentant un génotype homozygote pour un variant faux-sens dans le gène DDB2 (damage specific DNA binding protein 2) avaient un risque significativement plus élevé de développer un CE oculaire. Les objectifs de cette étude étaient de déterminer la fréquence de l'allèle à risque associé au CE dans le gène DDB2 dans les populations suisses et autrichiennes de Haflinger et de valider la corrélation phénotypique décrite précédemment. Pour ce faire, des Haflingers présentés dans différentes cliniques équines en Suisse (n = 21, dont 11 cas de CE), des Haflingers privés (n = 52, dont 1 cas de CE) et des Haflingers d'un haras du Tyrol autrichien (n = 53) ont été recrutés. Le génotype DDB2 individuel des animaux a été déterminé à l'aide d'un test de réaction en chaîne par polymérase (PCR) utilisant des échantillons de follicules pileux ou de sang total. Sur les 12 chevaux souffrant de CE, neuf avaient un CE oculaire et trois un CE non oculaire. Six des neuf Haflingers atteints de CE oculaire et un des trois Haflingers atteints de CE non oculaire étaient homozygotes pour la variante DDB2. Sur les 113 animaux cliniquement normaux, 7/113 étaient homozygotes (6 %) et 42/113 étaient hétérozygotes (37 %), ce qui correspond à une fréquence d'allèle de 24,8 % dans la cohorte de contrôle. Le risque de CE oculaire chez les Haflingers augmente de manière significative avec le génotype DDB2 homozygote. Cependant, tous les animaux atteints de CE ne sont pas porteurs de cette variante génétique et tous les animaux homozygotes DDB2 ne développent pas de CE, ce qui peut s'expliquer par la genèse multifactorielle de la maladie. En raison de la fréquence élevée de l'allèle indésirable, nous recommandons de tenir compte du génotype DDB2 individuel des animaux reproducteurs afin d'éviter une progéniture homozygote présentant un risque fortement accru de CE en excluant les accouplements à haut risque.

[Ocular and non-ocular squamous cell carcinomas in the Haflinger: Eight cases at the Institut Suisse de Médecine Equine (2015-2022)]. / Okuläre und nicht-okuläre Platten­-epithel­karzinome beim Haflinger: Acht Fälle am Institut Suisse de Médecine Equine (2015­2022).

INTRODUCTION: This case series describes the clinical course of ocular and non-ocular squamous cell carinoma (SCC) in the Haflinger horse and is intended to raise awareness of the high recurrence rate and tendency to metastasize. Eight Haflingers with histologically confirmed SCC were included, five ocular and three non-ocular, who were presented at the Institut Suisse de Médecine Équine (ISME) Bern between July 2015 and January 2022. The ocular SCC cases were all presented because of an apparent mass, which in most cases was post-treatment recurrence. The occurrence of recurrences was observed between 3 weeks and 16 years after initial therapy. Four of five Haflingers with ocular SCC had an enucleation, three of which were clinically normal at the time of the completion of this study, one case was euthanized due to confirmed metastases and one due to lameness. The result of enucleations for therapy of ocular SCC was good if no metastases occurred. Of the three non-ocular SCC cases, only one case, a penile SCC, had an apparent mass. Therapy was initiated in this case, while the other two cases were euthanized shortly after diagnosis due to the poor prognosis of SCC in the appropriate locations (maxillary sinus, mandible). Metastases occurred three and two years after removal of the primary tumor in ocular SCC in the scapula, liver and lungs and in non-ocular SCC from the penis to the nostrils. Since a postmortem pathological examination was not carried out on all Haflingers, further metastases cannot be ruled out. Haflingers with SCC should be monitored by a veterinarian over the long term, as recurrences and/or metastases can still occur years later.

INTRODUCTION: Cette série de cas décrit l'évolution clinique des carcinomes épidermoïdes (CE) oculaires et non oculaires chez le cheval Haflinger et vise à faire prendre conscience du taux de récidive élevé et de la tendance à la formation de métastases. Huit Haflinger avec un CE confirmé histologiquement, cinq oculaires et trois non-oculaires, qui ont été présentés à l'Institut Suisse de Médecine Équine (ISME) Berne entre juillet 2015 et janvier 2022, ont été inclus. Les cas de CE oculaires ont tous été présentés en raison d'une masse apparente, qui dans la plupart des cas était une récidive post-traitement. La survenue des récidives a été observée entre 3 semaines et 16 ans après le traitement initial. Quatre des cinq Haflinger atteints de CE oculaire ont subi une énucléation, dont trois étaient cliniquement normaux au moment de l'achèvement de l'étude, un cas ayant été euthanasié en raison de métastases confirmées et un autre en raison d'une boiterie. Le résultat des énucléations pour la thérapie du CE oculaire était bon s'il n'y avait pas de métastases. Sur les trois cas de CE non oculaires, seul un cas, un CE pénien, présentait une masse apparente. Le traitement a été initié dans ce cas, tandis que les deux autres cas ont été euthanasiés peu de temps après le diagnostic en raison du mauvais pronostic des CE dans les localisations constatées (sinus maxillaire, mandibule). Des métastases sont apparues trois et deux ans après l'ablation de la tumeur primaire dans le cas du CE oculaire, au niveau de l'omoplate, du foie et des poumons et, dans un cas de CE non oculaire, celui du pénis, aux narines. Étant donné que tous les Haflinger n'ont pas fait l'objet d'un examen pathologique post-mortem, on ne peut exclure la possibilité d'autres métastases. Les Haflinger atteints de CE doivent être suivis à long terme par un vétérinaire, car des récidives et/ou des métastases peuvent encore survenir des années plus tard.

The potential of three whole blood microRNAs to predict outcome and monitor treatment response in sarcoid-bearing equids.

MicroRNAs (miRNAs) have been proposed as biomarkers for equine sarcoid (ES) disease. In this study, the suitability of three whole blood miRNAs to diagnose ES and to predict and monitor the outcome of therapy was explored. Using reverse transcription-quantitative polymerase chain reaction (RT-qPCR), expression levels of eca-miR-127, eca-miR-379, and eca-miR-432 in whole blood of ES-affected equids before and at least one year after therapy were compared to those of unaffected control equids. Associations of age, sex, species, diagnosis, and therapy outcome with miRNA expression levels were examined using general linear models. In total, 48 ES-affected equids and 47 control equids were recruited. From the affected animals, 31 responded favorably to treatment, and 17 demonstrated a failure of therapy. None of the tested miRNAs were influenced by age. Male equids showed increased expression of eca-miR-127 compared to females and horses showed higher expression levels of eca-miR-379 and eca-miR-432 than donkeys. Eca-miR-127 was confirmed as a diagnostic discriminator between ES-affected and control equids. No difference in miRNA profiles before therapy was found when comparing ES-affected equids with success vs. failure of therapy. Eca-miR-379 and eca-miR-432 decreased over time in horses where therapy was successful, but not in those cases where it failed. Biological variables influence equine whole blood miRNA expression, which may complicate biomarker validation. While none of the tested miRNAs could predict the response to therapy in ES-affected equids and eca-miR-127 showed poor diagnostic accuracy for ES, eca-miR-379 and eca-miR-432 miRNAs might allow refinement of monitoring of success of ES therapy.

Mesenteric granulomas independently predict long-term risk of surgical recurrence in Crohn's disease.

AIM: The risk factors that predict surgical recurrence in Crohn's disease (CD) remain controversial. Postoperative anti-tumour necrosis factor (anti-TNF) therapy might lower recurrence rates whilst the presence of mesenteric granulomas has been postulated to increase the risk. We hypothesized that mesenteric granulomas indicate disease severity and might predict the risk of surgical recurrence, irrespective of immunosuppressive therapy. METHOD: We performed a retrospective review of all consecutive patients undergoing operations for CD between January 2000 and December 2014 at a single tertiary referral centre and assessed the perioperative factors and histological findings at the time of surgery. Surgical recurrence rates and the immunosuppressive regimen were assessed through retrospective chart review and telephone interviews. RESULTS: A total of 274 patients were eligible for analysis. Median follow-up was 8.54 (5.48-14.42) years. A total of 63 patients (23.0%) underwent surgery for recurrent CD after a median of 4.75 (2.10-7.96) years. In final histology, 35 (12.8%) patients had mesenteric granulomas. TNF inhibitors were administered postoperatively in 104 (38.0%) and thiopurines in 137 (50.0%) patients. In univariate analysis, only the presence of mesenteric granulomas [hazard ratio (HR) 1.95; 95% CI 1.05-3.62; P = 0.035] significantly increased the risk for recurrent surgery while postoperative anti-TNF (HR 0.85; 95% CI 0.49-1.50; P = 0.581) or thiopurine therapy (HR 1.03; 95% CI 0.61-1.73; P = 0.916) did not. In multivariate analysis, only the presence of mesenteric granulomas significantly influenced the risk of surgical recurrence (HR 1.94, 95% CI 1.04-3.60; P = 0.037). CONCLUSION: Intestinal and mesenteric granulomas should be differentiated in pathology reports, because mesenteric, but not intestinal, granulomas may be associated with an increased risk of surgical recurrence.

Genetic risk for squamous cell carcinoma of the nictitating membrane parallels that of the limbus in Haflinger horses.

Squamous cell carcinoma (SCC) is the most common cancer affecting the equine eye, with a higher incidence documented in Haflinger horses. Recently, a missense variant in the gene damage specific DNA binding protein 2 (DDB2, p.Thr338Met) on ECA12 was identified as a risk factor for the development of limbal SCC in Haflinger horses. SCC also occurs on the nictitating membrane; therefore, investigating the role of this missense variant in nictitating membrane SCC is warranted. In this study, a common ancestor was identified among Haflinger horses affected with limbal SCC or with nictitating membrane SCC, thus supporting a recessive risk factor for the development of cancer at both ocular locations. Analysis of genotype data from Haflinger horses with and without nictitating membrane SCC revealed that the same region on ECA12 associated with limbal SCC was also associated with nictitating membrane SCC (P < 2.04 × 10-5 ). Fine mapping of this locus using 25 cases and 49 controls supported the hypothesis that DDB2:c.1013C>T, p.Thr338Met, is a risk factor for nictitating membrane SCC, as 88% of our cases were homozygous for this variant and no other polymorphism was more strongly associated (P = 4.13 × 10-14 ). These data indicate that the genetic risk is the same for the development of both limbal and nictitating membrane SCC in Haflinger horses and validates utilization of genetic testing of the DDB2 variant for both clinical management and the guidance of mating decisions.

Effect of pathologist's dedication on lymph node detection rate and postoperative survival in colorectal cancer.

AIM: As adjuvant chemotherapy in colorectal cancer relies on the identification of lymph node metastases, the pathologist's dedication may have a considerable influence on postoperative survival. METHOD: The aim of this retrospective study was to assess the impact of the pathologist's dedication on lymph node detection rate and postoperative survival in patients operated on by a single experienced colorectal surgeon within a 5-year period. We assessed 229 patients undergoing total mesorectal excision or complete mesocolic excision by the senior author between 1 January 2009 and 31 December 2013. Pathologists were grouped as 'general pathologist' or 'dedicated pathologist' depending on their dedication/specialization. RESULTS: Dedicated pathologists found statistically significantly more lymph nodes in colorectal specimens than general pathologists [23 (interquartile range 24) vs 14 (interquartile range 11), respectively; P < 0.001]. The detection rate of ≥ 12 lymph nodes per specimen was significantly higher in the dedicated pathologist group [65/74 (87.8%) vs 105/155 (67.7%); P = 0.016]. However, postoperative survival did not differ in the respective subgroups. In the multivariable analysis by Cox proportional hazard model, International Union against Cancer Stage IV was the only factor associated with decreased disease-specific survival (hazard ratio 28.257; 95% CI 3.850-207.386; P = 0.001). CONCLUSION: In our centre, the pathologist's dedication has an impact on lymph node detection rate but does not influence postoperative disease-specific survival.

[Off-label biologic therapy of ANCA-associated and non-ANCA-associated small-vessel vasculitis : Efficacy and safety analysis of a national registry (GRAID2)]. / Off-label-Biologikatherapie von ANCA-assoziierten und nicht-ANCA-assoziierten Kleingefäßvaskulitiden : Wirksamkeits- und Sicherheitsanalyse eines nationalen Registers (GRAID2).

OBJECTIVE: To evaluate the clinical efficacy and safety of off-label biological therapies in patients with ANCA-associated vasculitis (AAV) and non-ANCA-associated small-vessel vasculitis (nAAV) in clinical practice. METHODS: The German Registry in Autoimmune Diseases 2 (GRAID2) is a national, retrospective, non-interventional, multicentre observational study (August 2006 until December 2013) on patients with autoimmune diseases refractory to standard immunosuppressive therapy treated with off-label biologicals. RESULTS: Data from 64 patients (20.6% of all GRAID2 patients) were collected: 54 patients (84.4%) had ANCA-associated vasculitis (AAV) and 10 patients (15.6%) had non-ANCA-associated small-vessel vasculitis (nAAV). Of the AAV patients, 96.3% were treated off-label with rituximab (RTX) and 3.7% with tumor necrosis factor alpha (TNFα)-inhibitors. Of patients with nAAV, 30% were treated with RTX, 60% with TNFα-inhibitors, and 10% with tocilizumab. The main reasons for off-label biological treatment in AAV patients were pulmonary, renal, or ear, nose, and throat involvement. These manifestations clearly improved in most patients after off-label biological therapy was initiated. Daily glucocorticoid dosage could be reduced. The off-label biological therapy was generally well tolerated. In AAV patients, 4.18 severe infections per 100 patient years were observed. There was one death in the nAAV group caused by fungal infection and ileus. A correlation between this fatality and RTX treatment was regarded as possible. CONCLUSION: Safety and efficacy of off-label RTX-treatment in AAV-patients could be assessed in the GRAID2 data. Results point to good efficacy and safety of RTX in this special patient cohort and support the approval of RTX for AAV induction therapy.

[Rituximab for the treatment of poly- and dermatomyositis : Results from the GRAID-2 registry]. / Rituximab zur Behandlung von Poly- und Dermatomyositis : Die Ergebnisse des GRAID-2-Registers.

INTRODUCTION: In the treatment of poly- and dermatomyositis, only a limited number of treatment modalities are established. OBJECTIVE: The goal of the GRAID-2 registry was to study off-label use of biologic drugs for this indication in Germany. PATIENTS AND METHODS: Analysis of the data of the GRAID-2 registry for poly- and dermatomyositis. RESULTS: In 22 of the 23 patients in the GRAID-2 registry, rituximab (RIX) was administered, while 1 patient was given tocilizumab as off-label therapy. The 22 patients who received RIX treatment were analyzed. At the start of treatment, the following active manifestations were present: myositis (n = 18), lung involvement (mainly interstitial lung disease; n = 10), arthritis (n = 10), skin manifestation (n = 9), and Raynaud syndrome (n = 5). Nine of the patients were Jo-1-antibody positive. All patients had previous treatments with multiple conventional immunosuppressive drugs. Treatment with RIX was given as infusions of 1 g i. v., which were repeated after 2 weeks. Patients received a mean of 3.09 ± 2.27 infusions (equivalent to 1.5 cycles of 2 × 1 g, max. 5 cycles). Tolerability of RIX treatment was rated as very good in 16 of 22 patients (72%), good in 5 (23%), and moderate in 1 (5%). In all, 27 adverse events were documented, with the majority being infections, whereby 2 severe infections occurred (6.59 per 100 patient-years). Eighty six percent of the patients showed complete remission of their myositis and 79% of their arthritis. The mean value of creatinine kinase in plasma fell from 1505 ± 2534 U/l before the start of treatment to 39 ± 134 U/l at the last visit. Regarding lung involvement, 1 of 10 of the patients showed complete and 6 of 10 partial remissions. In 2 of 10 patients, lung disease was stable during treatment. CONCLUSION: RIX is the preferred off-label biologic drug for poly- and dermatomyositis in Germany. In spite of a strongly pretreated group of patients, the tolerability is acceptable, although the patient number in this investigation is small. Moreover, the results lead to the assumption that the majority of the patients had a good or even very good therapeutic response to RIX.

Regulatory T Cells Promote Natural Killer Cell Education in Mixed Chimeras.

Therapeutic administration of regulatory T cells (Tregs) leads to engraftment of conventional doses of allogeneic bone marrow (BM) in nonirradiated recipient mice conditioned with costimulation blockade and mammalian target of rapamycin inhibition. The mode of action responsible for this Treg effect is poorly understood but may encompass the control of costimulation blockade-resistant natural killer (NK) cells. We show that transient NK cell depletion at the time of BM transplantation led to BM engraftment and persistent chimerism without Treg transfer but failed to induce skin graft tolerance. In contrast, the permanent absence of anti-donor NK reactivity in mice grafted with F1 BM was associated with both chimerism and tolerance comparable to Treg therapy, implying that NK cell tolerization is a critical mechanism of Treg therapy. Indeed, NK cells of Treg-treated BM recipients reshaped their receptor repertoire in the presence of donor MHC in a manner suggesting attenuated donor reactivity. These results indicate that adoptively transferred Tregs prevent BM rejection, at least in part, by suppressing NK cells and promote tolerance by regulating the appearance of NK cells expressing activating receptors to donor class I MHC.

Tacrolimus, Mycophenolate Mofetil, and Low-Dose Steroids With or Without Interleukin-2 Receptor Antibody Induction Therapy: A Retrospective Cohort Analysis.

BACKGROUND: Selective interleukin-2 receptor (IL2R) blockade is one option to decrease acute rejection rates in kidney transplant recipients. However, there are little data on the impact of basiliximab in a triple immunosuppressive regimen (tacrolimus, mycophenolate mofetil, and low-dose steroids). Thus, this analysis aims at investigating the impact of basiliximab induction on rejection rates and immediate graft function following kidney transplantation. METHODS: Basiliximab was introduced in our center according to our center's policy in the beginning of 2011. Patients who received basiliximab (n = 83) were compared with patients without induction therapy (n = 65) transplanted before the introduction of IL2R antibody induction. RESULTS: The use of basiliximab as induction therapy decreased the incidence of biopsy-proven acute rejection (BPAR) within the 1st year after transplantation (21.5% vs 14.5%; P = .283). Overall rejection episodes (including BPAR and borderline rejection) were significantly reduced in patients with basiliximab compared with patients without (41.5% vs 24.1%; P = .033). However, graft function (incidence of delayed graft function, primary nonfunction, slow graft function, and serum creatinine decline) and overall outcome (patient and graft survivals) were similar in both groups. CONCLUSIONS: We found a favorable impact of basiliximab induction therapy on early acute rejection rate. The impact on long-term outcome must be addressed in further randomized controlled trials.

Lung Sealing with the Sandwich-Technique: A New Surgical Method to Deal with the Emphysematous Lung.

UNLABELLED: The persistent air leak is a common and sometimes difficult to manage complication after major pulmonary resections. Especially in cases with lung emphysema spontaneous sealing of the lung surface under conservative therapy can be prolonged or even fail and a reoperation to close the damaged visceral pleura might be necessary. An ideal surgical solution to deal with this problem is not known, all of the techniques have advantages but also limitations and additional operations should be avoided in this group of frail patients. In this paper a new surgical method to seal the lung surface is presented based on two exemplary cases and our clinical experience. Basically, two stripes of fleece bounded fibrin based sealant are put on the visceral pleura parallel to the wound, which will be then closed by multiple stitches of absorbable suture line inserted through the stripes. Afterwards, a second layer of the same sealant will be placed over it to cover the suture with a narrow overlapping in all directions to the adjacent visceral pleura (Sandwich-Technique). In our experience, this technique can be used to successfully prevent or treat persistent air leaks especially in patients with lung emphysema in whom otherwise treatment options are limited. ABBREVIATIONS: VATS = video-assisted thoracoscopic surgery POD = postoperative day LVRS = lung volume reduction surgery FEV1 = forced expiratory volume in the first second DLCO = diffusing capacity of the lung for carbon monoxide.

Outcomes for split-thickness skin transplantation in high-risk patients using octenidine.

Skin transplantation is a commonly used surgical technique; however, the complication rate, including postoperative infection and delayed wound healing due to inefficient perfusion, is significantly higher in patients suffering from comorbidities. Hence, a subsequent repeat procedure is often necessary. In this report, two case studies are presented in which an octenidine-based antiseptic is used with a tie-over dressing (TOD) instead of povidone iodine (PVP-iodine), following a split-thickness skin graft. The two patients selected were deemed to be at high risk of impaired wound healing due to comorbidities. The first patient, a confirmed smoker with diabetes, presented with a nodular melanoma that was resected and covered with a split-thickness skin graft. After 5 days of negative pressure wound therapy as a TOD, in combination with PVP-iodine, the graft became necrotic. A second split-thickness skin graft was performed and an antiseptic regimen with octenidine in combination with the same TOD resulted in a completely healed transplant. The second patient, also a confirmed smoker with diabetes and receiving oral corticosteroid treatment, was diagnosed with a skin necrosis on her leg. Following the split-thickness skin graft, octenidine and TOD were applied. The patient's skin graft completely healed without any adverse events. These two case studies indicate that the combination of octenidine and TOD following split-thickness skin transplantation is safe, well-tolerated and appears to have positive benefits in the reconstruction of defects in patients with impaired wound healing.

Nodular epitheloid sarcoma of the upper limb. A case report and review of the literature.

Epitheloid sarcoma is a rare malignant soft tissue sarcoma. We present a 36-year-old male patient with a primary tumour on his wrist and subcutaneous spread in a sporotrichoid pattern along the upper extremity. Early surgical treatment with micrographic control of all margins provides best long term outcome as long as a solitary lesion is present. In case of cutaneous and internal spread of the disease treatment options are only palliative. Early diagnosis, therefore, is most crucial.

Implication for bone marrow derived stem cells in hepatocyte regeneration after orthotopic liver transplantation.

The liver has the outstanding ability to regenerate itself and restore parenchymal tissue after injury. The most common cell source in liver growth/regeneration is replication of preexisting hepatocytes although liver progenitor cells have been postulated to participate in liver regeneration in cases of massive injury. Bone marrow derived hematopoietic stem cells (BM-HSC) have the formal capacity to act as a source for hepatic regeneration under special circumstances; however, the impact of this process in liver tissue maintenance and regeneration remains controversial. Whether BM-HSC are involved in liver regeneration or not would be of particular interest as the cells have been suggested to be an alternative donor source for the treatment of liver failure. Data from murine models of liver disease show that BM-HSC can repopulate liver tissue and restore liver function; however, data obtained from human liver transplantation show only little evidence for liver regeneration by this mechanism. The cell source for liver regeneration seems to depend on the nature of regeneration process and the extent of injury; however, the precise mechanisms still need to be resolved. Current data suggest, that in human orthotopic liver transplantation, liver regeneration by BM-HSC is a rather rare event and therefore not of clinical relevance.

[Leg pain]. / Das schmerzhafte Bein.

Leg pain is a very common complaint in clinical medicine which deserves thorough investigation. All tissues of the lower leg are able to cause pain, each of them by different pathomechanisms. In the current review, all the different types of tissue, i.e., spine, neural plexus, peripheral nerves, muscles, and vasculature, are systematically covered. The different disease entities are explained in terms of pathophysiology and clinical picture. Diagnostic measures and pathways are sketched, as well as therapeutic approaches in some instances. Diseases of the bone and joint are omitted since they are the subject of orthopedic surgery.

[Leg ulcers]. / Ulcus cruris.

The lower leg is in particular prone to the development of ulceration. Many different causes may lead to ulceration. Thus, a thorough diagnosis is mandatory, and a biopsy is often required. By far the most common type is the classical venous ulcer due to chronic venous insufficiency, located at the medial ankle. A more complicated-and more difficult to treat-type of venous ulcer is arthrogenic congestion syndrome with its extreme variant of a "legging" ulcer. In cases with severe peripheral arterial disease, an arterial ulcer may develop. The hypertensive ulcer Martorell is associated with arterial hypertension and diabetes; the underlying pathology is occlusion of arteriolar vessels. A typical diabetic ulceration is the necrobiosis lipoidica. Important differential diagnoses of leg ulceration include pyoderma gangrenosum and the calciphylactic ulcer. Due to a long-standing course, an ulceration may turn malignant. Vice versa, ulceration may occur as sign of a primary malignant lesion.

[Clinical symptoms and therapy of necrotizing skin and soft tissue infections]. / Klinik und Therapie nekrotisierender Haut- und Weichgewebsinfektionen.

Skin and soft tissue infections are among the most common diseases requiring surgical treatment. The presentation of patients varies from folliculitis to severe necrotizing infections with a fatal outcome. The diagnosis of a necrotizing infection is often difficult. The correct diagnosis is often made after deterioration of the patient's condition in the rapid course of the disease. The early and correct diagnosis and immediate surgery are decisive for the prognosis. Treatment at a specialized intensive care unit and the administration of a broad spectrum antibiotic are pivotal for the survival of individual patients.

Intensified surveillance after surgery for colorectal cancer significantly improves survival.

BACKGROUND: Postoperative surveillance after curative resection for colorectal cancer has been demonstrated to improve survival. It remains unknown however, whether intensified surveillance provides a significant benefit regarding outcome and survival. This study was aimed at comparing different surveillance strategies regarding their effect on long-term outcome. METHODS: Between 1990 and 2006, all curative resections for colorectal cancer were selected from our prospective colorectal cancer database. All patients were offered to follow our institution's surveillance program according to the ASCO guidelines. We defined surveillance as "intensive" in cases where >70% appointments were attended and the program was completed. As "minimal" we defined surveillance with <70% of the appointments attended and an incomplete program. As "none" we defined the group which did not take part in any surveillance. RESULTS: Out of 1469 patients 858 patients underwent "intensive", 297 "minimal" and 314 "none" surveillance. The three groups were well balanced regarding biographical data and tumor characteristics. The 5-year survival rates were 79% (intensive), 76% (minimal) and 54% (none) (OR 1.480, (95% CI 1.135-1.929); p <0.0001), respectively. The 10-year survival rates were 65% (intensive), 50% (minimal) and 31% (none) (p <0.0001), respectively. With a median follow-up of 70 months the median time of survival was 191 months (intensive), 116 months (minimal) and 66 months (none) (p <0.0001). After recurrence, the 5-year survival rates were 32% (intensive, p = 0.034), 13% (minimal, p = 0.001) and 19% (none, p = 0.614). The median time of survival after recurrence was 31 months (intensive, p <0.0001), 21 months (minimal, p <0.0001) and 16 month (none, p <0.0001) respectively. CONCLUSION: Intensive surveillance after curative resection of colorectal cancer improves survival. In cases of recurrent disease, intensive surveillance has a positive impact on patients' prognosis. Large randomized, multicenter trials are needed to substantiate these results.

[Three-dimensional reconstruction of central lung tumors based on CT data]. / Dreidimensionale Rekonstruktion von zentralen Lungentumoren basierend auf CT-Daten : Erste klinische Erfahrungen First clinical experiences.

BACKGROUND: CT scanning of the lungs is the standard procedure for preoperative evaluation of central lung tumors. The extent of the tumor and infiltration of central lung structures or lung segments are decisive parameters to clarify whether surgery is possible and the extent of resection. With computer-assisted methods for the segmentation of anatomical structures based on CT data (Fraunhofer MeVis, Bremen) an enhanced, three-dimensional selective visualization is now possible. PATIENTS AND METHODS: From August 2007 through June 2009, 22 patients with central lung tumors were treated at the department of thoracic surgery, University of Schleswig-Holstein, campus Lübeck. There were 15 males and 7 females with a mean age of 60.2 years (range 41-74 years), 18 patients had a long history of smoking, while 4 patients had never smoked. Of the patients 20 had a primary lung carcinoma, 1 patient had local recurrent lung cancer after lobectomy and 1 patient had a central lung metastasis from a non-pulmonary primary carcinoma. A multi-slice detector computer tomogram (MSDCT) scan was performed in all cases. All data were three-dimensionally reconstructed and visualized using special computer-aided software (Fraunhofer MeVis, Bremen). Pulmonary lung function tests, computed postoperative lung volume, bronchoscopic findings, general condition of the patients and the three-dimensionally reconstructed CT data were used for an individual risk analysis and surgical planning. RESULTS: According to the risk analysis 14 out of the 22 patients were surgically treated, 7 patients were staged as functionally inoperable and 1 as technically inoperable. A pneumonectomy was performed in 5 cases, a lobectomy/bilobectomy in 4 cases, an extended lobectomy in 3 cases and 1 case each of a wedge resection and a sleeve resection. Of the 14 patients 2 were classified as stage Ia/b, 7 patients as stage IIa/b and 5 patients as stage IIIa. The median length of time spent in hospital was 8.5±33 days and the mortality rate was 0%. The three-dimensional visualization of the tumor and its anatomical relationship to central pulmonary vessels and the airway system was feasible in all cases. The three-dimensional reconstruction was confirmed in all cases by surgical exploration. CONCLUSION: Three-dimensional reconstruction of CT scan data is a new and promising method for preoperative presentation and risk analysis of central lung tumors. The three-dimensional visualization with anatomical reformatting and color-coded segmentation enables the surgeon to make a more precise strategic approach for central lung tumors.

[Current application of osteoporosis guidelines--expert recommendations of the German Society of Orthopaedic Surgery and Traumatology]. / Umsetzung der Osteoporoseleitlinien in Orthopädie und Unfallchirurgie--Ergebnisse eines Expertenworkshops der DGOU.

AIM: As an increasing number of patients suffer from osteoporosis-related disorders worldwide, the medical as well as the socioeconomic impact of this problem is significant. Although evidence-based guidelines for diagnosis and treatment are available, their application in daily practice is insufficient. The aim of our initiative was to develop a strategy for supporting this transfer. METHODS: An expert group of the German Society of Orthopaedics and Traumatology (DGOU) has analysed the current scientific as well as health-care data bases regarding diagnosis and treatment of osteoporosis. Then a set of recommendations has been developed in order to improve this situation. RESULTS: The identified support strategy will focus on better identification of patients with osteoporosis and frailty, enhanced interdisciplinary approaches and increased activity to disseminate available guidelines. Additionally, more research activities are necessary in order to highlight the socioeconomic burden of the disease and to continuously improve surgical treatment strategies in the future. CONCLUSION: To ensure a successful application of the recommendations, continuous support of involved health professionals as well as political institutions, national health insurance systems, scientific societies and patient organisations is necessary.