Surgical margin clearance and extended chemotherapy defines survival for synchronous oligometastatic liver lesions of the ductal adenocarcinoma of the pancreas.

BACKGROUND: The role of surgery for circumscribed synchronous hepatic lesions of the pancreatic ductal adenocarcinoma (PDAC) remains controversial. Thus, the aim of our study was to compare survival outcome (OS) after surgery of patients with hepatic metastases (M1surg) to patients with only localized disease. METHODS: Correlation analysis of clinicopathological data and OS after resection of M1surg patients and patients with localized PDACs (M0) was performed. Patients were included for survival analysis only if a complete staging including perineural, venous and lymphatic invasion was available. RESULTS: Out of the study collective, 35 patients received extended surgery (M1surg), whereas 131 patients received standardized surgery for localized disease (M0). Length of hospitalization and mortality was similar in both groups. FOLFIRNOX as an adjuvant treatment regime was administered in ~ 23 and ~ 8% of M1surg and M0 patients, respectively. In subgroup analysis of R0 resected patients and in multivariate analysis of the total cohort, there was no difference in overall survival between both groups. Only the resection status (R1 vs R0) and venous invasion (V1) were identified as independent prognostic factors. Site of recurrence in R0 resected M1surg patients and in M0 patients were homogenously distributed. CONCLUSION: This is the first study demonstrating a survival benefit after extended surgery for synchronously hepatic-metastasized PDACs. We found no difference in survival outcome of metastasized patients when compared to patients with localized disease. FOLFIRINOX as an adjuvant treatment regime for resected M1surg presumably is worthwhile. Larger multicenter studies are still needed to validate our results.

Mesopancreatic excision for pancreatic ductal adenocarcinoma improves local disease control and survival.

BACKGROUND: Survival in ductal adenocarcinoma of the pancreatic head (hPDAC) is poor. After implementation of the circumferential resection margin (CRM) into standard histopathological evaluation, the margin negative resection rate has drastically dropped. However, the impact of surgical radicality on survival and the influence of malignant infiltration of the mesopancreatic fat remains unclear. At our institution, a standardized dissection of the mesopancreatic lamina and peri-pancreatic vessels are obligatory components of radical pancreatoduodenectomy. The aim of our study was to histopathologically analyze mesopancreatic tumor infiltration and the influence of CRM-evaluated resection margin on relapse-free and overall survival. METHOD: Clinicopathological and survival parameters of 264 consecutive patients who underwent surgery for hPDAC were evaluated. RESULTS: The rate of R0 resection R0(CRM-) was 48.5%, after the implementation of CRM. Mesopancreatic fat infiltration was evident in 78.4% of all consecutively treated patients. Patients with mesopancreatic fat infiltration were prone to lymphatic metastases (N1 and N2) and had a higher rate of positive resection margin (R1/R0(CRM+)). In multivariate analysis, only R0 resection was shown to be an independent prognostic parameter. Local recurrence was diagnosed in only 21.1% and was significantly lower in patients with R0(CRM-) resected hPDACs (10.9%, p < 0.001). CONCLUSION: Mesopancreatic excision is justified, since mesopancreatic fat invasion was evident in the majority of our patients. It is associated with a significantly improved local tumor control as well as longer relapse-free and overall survival.

Quantitative signal intensity ratios to distinguish between subfascial lipoma and atypical lipomatous tumor/well-differentiated liposarcoma using short-tau inversion recovery (STIR) MRI.

PURPOSE: To establish simple quantitative variables at short-tau inversion recovery (STIR) magnetic resonance imaging (MRI) to identify lipomas with high specificity in patients with indeterminate subfascial lipomatous tumors. MATERIALS AND METHODS: The MRI examinations of 26 patients (14 men, 12 women; mean age 63±12.5 [SD] years; range: 40-84years) with histopathologically proven subfascial atypical lipomatous tumors/well-differentiated liposarcomas (ALT/WDLs) and those of 68 patients (32 men, 36 women; mean age, 56±13.5 [SD] years; range: 21-83years) with lipomas were retrospectively reviewed. Ratios derived from region of interest based signal intensity (SI) measurements of tumors and adjacent fat on STIR images were calculated and maximum tumor diameters were noted. Diagnostic parameter capabilities were assessed using ROC curve analysis. Interreader agreement was evaluated by calculation of intraclass correlation coefficients (ICC). RESULTS: Using a cut-off value of 1.18, STIR-SI ratios allowed discriminating between lipoma and ALT/WDL (AUC=0.88; P<0.001) yielding 93% specificity (95% CI: 77-99%) and 74% sensitivity (95% CI: 61-84%) for the diagnosis of lipoma. Interreader agreement was excellent (ICC=0.93). A significant difference in maximum tumor diameter was found between ALT/WDLs (mean: 18.1±6.0 [SD] cm; range: 5.6-33.1cm) and lipomas (mean: 9.7±5.0 [SD] cm; range: 2.9-29.1cm) (P<0.001). Using a cut-off of 11cm, maximum tumor diameter allowed discriminating between lipoma and ALT/WDLs with 92% specificity (95% CI: 75-99%) and 69% sensitivity (95% CI: 57-80%). The combination of a STIR-SI ratio<1.4 and maximum tumor diameter<11cm yielded 100% specificity (95% CI: 87-100%) and 65% sensitivity (95% CI: 54-77%) for the diagnosis of lipoma. CONCLUSION: The combination of STIR-SI ratio and maximum diameter allows discriminating between lipoma and ALT/WDL in initially indeterminate lipomatous tumors.

[Slipped capital femoral epiphysis-etiology and pathogenesis]. / Epiphyseolysis capitis femoris ­ Ätiologie und Pathogenese.

BACKGROUND: Slipped capital femoral epiphysis (SCFE) is the most significant hip disease in adolescence. Because of its typical occurrence at the time of the pubertal growth spurt and some particular clinical symptoms, it has been a topic of special interest in orthopedic research for a long time. A large number of etiological factors have been described, however their meaning in detail is still controversial. OBJECTIVES: After a short summary of the structure and function of the epiphysis, an overview of concepts in the pathogenesis of SCFE is given. MATERIALS AND METHODS: A selective review of literature was performed. RESULTS: Etiology of SCFE includes genetic, endocrinologic, histochemical and biomechanical factors. During puberty, obesity together with reduced femoral antetorsion are the main risk factors for the disease. The rarer atypical SCFE is closely related to metabolic disorders or other chronical diseases. The pathogenesis is characterized by the disproportion between the load-bearing capacity of the epiphysis and the acting forces on the proximal femur. CONCLUSIONS: The concept of the multifactorial etiology of SCFE is convincing. The susceptibility of the femoral epiphysis is explained considering the remarkable biomechanic local forces. The initial damage can be shown on the histological and the histochemical level. Important new aspects refer to the leptin-metabolism. However, in the majority of cases, biomechanical factors seem to be more significant than endocrinological phenomena. A complete understanding has not succeeded to date.

Meta-analysis of totally extraperitoneal inguinal hernia repair in patients with previous lower abdominal surgery.

BACKGROUND: Previous lower abdominal surgery is considered a relative contraindication to laparoscopic totally extraperitoneal (TEP) inguinal hernia repair. This was a meta-analysis of studies comparing the feasibility and safety of TEP repair between patients with (PS), and without (NS) a history of lower abdominal surgery. METHODS: A systematic literature search was undertaken for studies comparing the outcome of TEP inguinal hernia repair in patients with, and without previous lower abdominal surgery. Data on postoperative outcomes were extracted and compared by meta-analysis. Odds ratios (ORs) and mean differences with 95 per cent confidence intervals were calculated. RESULTS: Seven comparative cohort studies were identified, involving a total of 1657 procedures (PS 326, NS 1331). There was a statistically significant difference between PS and NS favouring the NS group with regard to both primary outcomes: intraoperative morbidity (OR 2·85, 95 per cent c.i. 1·19 to 6·80; P = 0·02; 7 studies; I2 = 33 per cent), and postoperative morbidity in the multiport subgroup (OR 2·14, 1·28 to 3·58; P = 0·004; 5 studies; I2 = 0 per cent). For the secondary endpoints conversion rate, peritoneal tears, major intraoperative bleeding, postoperative haematoseroma and delay in return to normal activities, there was a statistically significant difference favouring the NS group. CONCLUSION: This study suggests that patients with previous lower abdominal surgery who need hernia repair get less benefit from TEP repair than those with no history of surgery.

A new technique for correction of leg length discrepancies in combination with complex axis deformities of the lower limb using a lengthening nail and a locking plate.

PURPOSE: Intramedullary lengthening nails are an accepted alternative to external fixators but are limited by anatomical preconditions. Therefore, to date the use of external fixators is sometimes inevitable. We report on a new technique for correction of combined limb length discrepancies and complex axis deformities using solely internal devices - a lengthening nail and a locking plate. METHODS: Between October 2008 and November 2011 five patients (two femora, three tibias) with a mean leg length discrepancy of 36 mm (25 to 50) and a complex angular deformity were treated with a fully implantable motorized lengthening nail (Fitbone) and a locking plate. All patients were evaluated with regards to the pre- and postoperative leg length as well as axis alignment, functional outcome, lengthening indices and complications. RESULTS: A successful leg length equalization was achieved in all cases and physiological joint orientation angles in all but one case. The mean distraction index was 1.2 mm/day, the maturation index 24 days/cm and the consolidation index 35 days/cm. The functional outcome was very encouraging in all cases with bilateral free range of movement. In total, two complications were observed, one nonunion and one loss of leg length after an early locking bolt removal in a peripheral hospital. CONCLUSION: The combination of a fully implantable motorized lengthening nail and a locking plate is a valuable alternative option for treating selected cases with limb length discrepancies in combination with a complex deformity of the lower leg. However, the reported technique puts high demands on the preoperative planning, operative technique as well as surgeon's skills. LEVEL OF EVIDENCE: IV (retrospective series).

[Extracorporeal irradiation : Reimplantation of bone segments in the treatment of malignant bone tumours]. / Die extrakorporale Bestrahlung : Replantation von Knochensegmenten bei malignen Knochentumoren.

BACKGROUND: Malignant bone tumors themselves and the wide resection required because of them may cause huge bone defects in the bone segment involved. Autologous bone grafts are a reliable option to cover these defects in many cases but their availability is limited. Besides common alternative reconstruction methods, including the use of allografts and/or prostheses, especially extracoroporeal irradiation (ECI) and reimplantation of the bone segment involved is attracting increasingly more attention nowadays. DISCUSSION: In the following, we report on indications/contraindications, details of the operative technique, as well as the recommended rehabilitation regime of ECI. Furthermore, we compare our own results with those published in the recent literature. Especially the advantages and disadvantages of this method, the risks and the complications are illustrated and critically discussed. CONCLUSION: Extracorporeal irradiation of a tumor bearing bone segment is a valuable alternative reconstruction technique following tumor resections of the pelvis, femur and tibia, with encouraging results with respect to local control, complication risks and functional outcome.

Treatment of shepherd's crook deformity in patients with polyostotic fibrous dysplasia using a new type of custom made retrograde intramedullary nail: a technical note.

AIMS: The severe form of coxa vara, the 'shepherd's crook deformity', is always a consequence of a locally extensive form of polyostotic fibrous dysplasia (or McCune-Albright syndrome). Treatment of this deformity is a challenge. The soft bone does not tolerate any implant that depends on the stability of the cortical bone (like plates or external fixators). Intramedullary nails are the most appropriate implants for stabilisation, but if they are inserted from the greater trochanter, they cannot correct the varus deformity enough. PATIENTS AND METHODS: We have developed a special intramedullary nail that can be inserted from the osteotomy site and can be driven retrograde into the femoral neck in an appropriate valgus position. We have operated 15 legs in 13 patients. The average age at surgery was 14 years and 5 months (6 to 28.9). In all, 11 femora had been operated before (unsuccessfully) with various implants. RESULTS: The average follow-up was 54.2 months (7 to 132). The average correction of the neck/(distal) shaft angle was 57.5° (10° to 80°) ( = 72.8%). While pre-operatively none of the patients was able to walk without aid, at follow-up only one patient was unable to walk, three used the aid of crutches because of tibial lesions and one patient had an increased external rotation of the leg. At follow-up, most patients were free of pain. One implant broke and had to be replaced. CONCLUSION: This new operative method offers the possibility of efficient correction and stabilisation of this severe and difficult deformation.

Extraskeletal osteosarcoma: A European Musculoskeletal Oncology Society study on 266 patients.

PURPOSE: Prognosis of extraskeletal osteosarcoma (ESOS) is reported to be poorer than that of skeletal osteosarcoma. This multicenter retrospective study aimed to evaluate factors influencing ESOS prognosis. PATIENTS AND METHODS: Members of the European Musculoskeletal Oncology Society (EMSOS) submitted institutional data on patients with ESOS. RESULTS: Data from 274 patients treated from 1981 to 2014 were collected from 16 EMSOS centres; 266 patients were eligible. Fifty (18.7%) had metastases at diagnosis. Of 216 patients with localised disease, 211 (98%) underwent surgery (R0 = 70.6%, R1 = 27%). Five-year overall survival (OS) for all 266 patients was 47% (95% CI 40-54%). Five-year OS for metastatic patients was 27% (95% CI 13-41%). In the analysis restricted to the 211 localised patients who achieved complete remission after surgery 5-year OS was 51.4% (95% CI 44-59%) and 5-year disease-free survival (DFS) was 43% (95% CI 35-51%). One hundred twenty-one patients (57.3%) received adjuvant or neoadjuvant chemotherapy and 80 patients (37.9%) received radiotherapy. A favourable trend was seen for osteosarcoma-type chemotherapy versus soft tissue sarcoma-type (doxorubicin ± ifosfamide) regimens. For the 211 patients in complete remission after surgery, patient age, tumour size, margins and chemotherapy were positive prognostic factors for DFS and OS by univariate analysis. At multivariate analysis, patient age (≤40 years versus >40 years) (P = 0.05), tumour size (P = 0.0001) and receipt of chemotherapy (P = 0.006) were statistically significant prognostic factors for survival. CONCLUSION: Patient age and tumour size are factors influencing ESOS prognosis. Higher survival was observed in patients who received perioperative chemotherapy with a trend in favour of multiagent osteosarcoma-type regimen which included doxorubicin, ifosfamide and cisplatin.

Impact of Single Center Treatment on Ewing Sarcoma 10-Year Long Term Survival Rates.

PURPOSE OF THE STUDY Ewing sarcomas (ES) are the second most common solid malignant bone tumors in both, children and adolescents, and systemic chemotherapy protocols were established during the last 3 decades which proved to be a successful approach in addition to local treatment. The purpose of the present study is (i) to provide survival rates and prognostic factors for patients with ES which received treatment in a single center and (ii) to compare data with results of multicenter studies. MATERIALS AND METHODS Patients (n = 38) were treated by the same surgeon whereas surgery was combined with radiotherapy in 55.3% of the patients (n = 21). Median age at diagnosis was 17.5 years (4.7-60) and the median follow-up time for all patients was 8.2 years (9.8 years for survivors, 3.2 years for non-survivors). RESULTS The survival rate for metastasis free sarcoma decreases from 90.5% to 50% for patients diagnosed with disseminated disease stage. Patients with a good response to chemotherapy survived in 83.3% of the cases. In addition, a higher OS was found for patients younger than 15 years (82.4%) when compared to patients older than 15 years (73.3%). In contrast, multicenter studies reported lower survival rates for metastasis free (~60%) and metastasis stages (< 40%). DISCUSSION The survival rates in the present single center study are higher than the rates reported from multi-center studies although same chemotherapy protocols were used and no substantially difference are apparent for patient population. CONCLUSIONS Based on the present data we re-emphasize that patients with Ewing sarcoma receive appropriate treatment in a large and qualified center particularly considering the survival rates. In addition, our data underline that a close collaboration between the oncological team and the experienced surgeon is crucial for patient's care. Key words: Ewing sarcoma, survival rate, single center, prognostic factors, chemotherapy, surgery, multi center, single center.

The histone demethylase KDM4B regulates peritoneal seeding of ovarian cancer.

Epithelial ovarian cancer (EOC) has poor prognosis and rapid recurrence because of widespread dissemination of peritoneal metastases at diagnosis. Multiple pathways contribute to the aggressiveness of ovarian cancer, including hypoxic signaling mechanisms. In this study, we have determined that the hypoxia-inducible histone demethylase KDM4B is expressed in ∼60% of EOC tumors assayed, including primary and matched metastatic tumors. Expression of KDM4B in tumors is positively correlated with expression of the tumor hypoxia marker CA-IX, and is robustly induced in EOC cell lines exposed to hypoxia. KDM4B regulates expression of metastatic genes and pathways, and loss of KDM4B increases H3K9 trimethylation at the promoters of target genes like LOXL2, LCN2 and PDGFB. Suppressing KDM4B inhibits ovarian cancer cell invasion, migration and spheroid formation in vitro. KDM4B also regulates seeding and growth of peritoneal tumors in vivo, where its expression corresponds to hypoxic regions. This is the first demonstration that a Jumonji-domain histone demethylase regulates cellular processes required for peritoneal dissemination of cancer cells, one of the predominant factors affecting prognosis of EOC. The pathways regulated by KDM4B may present novel opportunities to develop combinatorial therapies to improve existing therapies for EOC patients.

Intramedullary lengthening nails: can we also correct deformities?

Unlike external fixators, the use of solid intramedullary lengthening nails is restricted to defined anatomical preconditions, such as an adequate bone length. Furthermore, all deformity corrections except the lengthening procedure have to be implemented intraoperatively and cannot be adjusted postoperatively. Conversely, even complex deformity corrections can be performed using intramedullary devices after a thorough preoperative planning. For preparation of the intramedullary cavity as well as positioning of the lengthening nail according to the preoperative planning, reaming the medullary canal with rigid reamers which don't follow the line of least resistance is inevitable. However, the application of solid lengthening nails might be limited, especially in children with ongoing epiphyseal growth, although a central perforation of the growth plate was shown to have no adverse effects on the growth potential. In cases with complex or multilevel deformities, an additional osteotomy and locking plate fixation could sometimes be a valuable solution in order to avoid external fixation. The low complication rate as well as the reduced compromising of soft tissues and periosteum render intramedullary lengthening nails the state-of-the-art procedure for limb lengthening in combination with deformity correction in patients who meet the anatomical preconditions.

[Acetabuloplasty - The Dega and Pemberton technique]. / Beckenosteotomie nach Dega und Pemberton.

BACKGROUND: Hip dysplasia is the most common congenital deformity requiring surgical correction osteotomy in order to prevent early onset of secondary hip arthrosis. The shape of the acetabulum can be modified by Dega or Pemberton osteotomy and is indicated for hip dysplasia and luxation with irregularities of the socket for children aged between 2 and 12 when the y­physis is still open. METHOD: We will describe indication, contra-indication, preoperative planning as well as details of the Pemberton technique. In addition, we will provide practical advice based on our long-standing experience. RESULTS: We present long-term results from the literature and also from our department. In addition, we will explain and critically discuss our own experiences and the risks and complications of surgical techniques. Good long-term results are reported for acetabuloplasties and Salter osteotomy which are preferred for surgical treatment of hip dysplasia in early life. Advantages and disadvantages of both surgical techniques will be compared in the discussion section. CONCLUSION: Dega and Pemberton acetabuloplasty shows good long-term results regarding prevention of a secondary coxarthrosis. However, correct indication is crucial since this surgical technique is more difficult compared to Salter osteotomy but is also associated with a higher correction potential and a lower complication rate.

Multifunctional poly(methacrylate) polyplex libraries: A platform for gene delivery inspired by nature.

Polymer-based gene delivery systems have enormous potential in biomedicine, but their efficiency is often limited by poor biocompatibility. Poly(methacrylate)s (PMAs) are an interesting class of polymers which allow to explore structure-activity relationships of polymer functionalities for polyplex formation in oligonucleotide delivery. Here, we synthesized and tested a library of PMA polymers, containing functional groups contributing to the different steps of gene delivery, from oligonucleotide complexation to cellular internalization and endosomal escape. By variation of the molar ratios of the individual building blocks, the physicochemical properties of the polymers and polyplexes were fine-tuned to reduce toxicity as well as to increase activity of the polyplexes. To further enhance transfection efficiency, a cell-penetrating peptide (CPP)-like functionality was introduced on the polymeric backbone. With the ability to synthesize large libraries of polymers in parallel we also developed a workflow for a mid-to-high throughput screening, focusing first on safety parameters that are accessible by high-throughput approaches such as blood compatibility and toxicity towards host cells and only at a later stage on more laborious tests for the ability to deliver oligonucleotides. To arrive at a better understanding of the molecular basis of activity, furthermore, the effect of the presence of heparan sulfates on the surface of host cells was assessed and the mechanism of cell entry and intracellular trafficking investigated for those polymers that showed a suitable pharmacological profile. Following endocytic uptake, rapid endosomal release occurred. Interestingly, the presence of heparan sulfates on the cell surface had a negative impact on the activity of those polyplexes that were sensitive to decomplexation by heparin in solution. In summary, the screening approach identified two polymers, which form polyplexes with high stability and transfection capacity exceeding the one of poly(ethylene imine) also in the presence of serum.

[Prognostic Value of Preoperative Anaemia and Perioperative Blood Transfusion in Surgical Treatment of Rectal Cancer]. / Prognostischer Wert präoperativer Anämie und perioperativer Fremdbluttransfusion in der chirurgischen Therapie des Rektumkarzinoms.

INTRODUCTION: There is evidence for the prognostic value of perioperative blood transfusion in the surgical treatment of patients with rectal cancer in the current literature. Also preoperative anaemia seems to have an impact on the outcome of these patients. The aim of this study was to evaluate the impact of preoperative anaemia and perioperative blood transfusion in patients with rectal cancer treated in our hospital. PATIENTS AND METHODS: 208 patients (81 females, 127 males; median age, 67 years) with rectal cancer were included in this retrospective study. All patients received surgical treatment. In 75 % of the patients an anterior rectum resection was performed while 25 % received an abdominoperineal rectum exstirpation. Patients with neoadjuvant treatment were included and statistical analyses were performed. RESULTS: 107 (51.4 %) patients exhibited preoperative anaemia. Patients with neoadjuvant treatment presented with significantly lower preoperative Hb (haemoglobin) values than patients without neoadjuvant treatment (p = 0.022). Patients with preoperative anaemia received significantly more blood transfusions (p = 0.001), had significantly longer hospital stays (p = 0.023) and significantly lower 5-years overall survival (p = 0.005). Blood transfusion was necessary in 82 patients (39.4 %). These patients presented with a significantly higher rate of perioperative complications (p = 0.01) and a lower 5-years overall survival (p = 0.002). In multivariate analyses neither preoperative anaemia nor perioperative transfusion was a significant prognostic factor. CONCLUSION: In our study preoperative anaemia and perioperative blood transfusion seems to have an impact on outcome of surgical treatment of patients with rectal cancer. However, in multivariate analyses neither preoperative anaemia nor perioperative transfusion was a significant prognostic factor.

Encapsulation status of papillary thyroid microcarcinomas is associated with the risk of lymph node metastases and tumor multifocality.

The management of papillary microcarcinoma (PMC) of the thyroid is controversial, especially after partial thyroid resection for benign thyroid disease. In order to detect prognostic factors for PMC, we analyzed 116 patients with PMC for encapsulation status and lymph node metastases. Between 10/1992 and 12/2010, 116 patients with PMC have been operated in our department (87 females, 29 males, median age 49 years). Eighty per cent of PMCs were diagnosed postoperatively. Seventy-six patients (66%) received a more extended resection with either thyroidectomy, near total thyroidectomy, or Dunhill operation either primarily or after completion operation, whereas 40 patients (34%) had only partial resection. Fifty patients (43%) received radioiodine (RIA) ablation. Lymph node metastases were found in 21 patients (18%). Univariate analysis showed four risk factors to be significantly associated with the risk of lymph node metastasis (p<0.05): male gender, younger age, age group<50 years and nonencapsulation of the tumor. Multivariate analysis demonstrated statistical significance for gender and tumor capsulation status. The tumor capsulation status also correlated with tumor multifocality. Our data show that the risk of lymph node metastases is significantly higher in partially or nonencapsulated PMC than in encapsulated specimens. We therefore suggest that the WHO classification should be extended to a compulsory notification of the encapsulation status in PMC.

Do malignant bone tumors of the foot have a different biological behavior than sarcomas at other skeletal sites?

We analyze the delay in diagnosis and tumor size of malignant bone tumors of the foot in a retrospective study. We compared the oncological and surgical long-term results with identical tumor at other anatomical sites in order to analyze the biological behavior of sarcomas that are found in the foot. Thirty-two patients with a histologically proven malignant bone tumor (fifteen chondrosarcomas, nine osteosarcomas, and eight Ewing sarcomas) between the years 1969 and 2008 were included. The median follow-up was 11.9 years. The overall median time gap between the beginning of symptoms and diagnosis in the study group was 10 months. Ewing sarcoma presented with the longest delay in diagnosis (median of 18 months), followed by osteosarcoma (median of 15 months) and chondrosarcoma (median of 7.5 months). The delay in diagnosis of these tumors was significantly longer than that of equivalent tumors at other skeletal sites, but the 5- and 10-year survival rates and the occurrence of distant metastases were comparable. In contrast, the average size of foot tumors was 5- to 30-fold less than that of tumors analyzed at other skeletal sites. This study indicates that sarcomas of the foot demonstrate a distinct biological behavior compared to the same tumor types at other skeletal sites.

Secondary malignancy in patients with sporadic neuroendocrine neoplasia.

The incidence of neuroendocrine neoplasias (NENs), especially of the gastro-entero-pancreatic (GEP), system relatively increased over the past decades, as a result of advanced diagnostic tools, a better clinical awareness, and distinguished pathological diagnostic recognition. Previous reports hypothesized an increased risk for secondary malignancies in patients with NEN especially in GEP-NENs. The present study was designed to investigate the coincidence of NENs and secondary malignancies in a large patient collective. A retrospective analysis was performed on 161 patients (85 female and 76 male) with NEN of various origins. Clinical data of these patients, different classification systems (TNM/WHO), proliferations-based grading, and clinical follow-up were collected and analyzed. Out of 143 patients with a sporadic NEN, 15 (10.49 %) patients were identified with secondary malignant tumors. Median age at the time of the primary operation for NEN was 65 years, whereas the median age of initial diagnosis of associated tumors was 59 years. Mean follow-up time was 61 months. The risk of developing a secondary malignancy was most elevated for patients with an NEN of the lung, the stomach, and the ileum (60, 50 and 20 %, respectively). The spectrum of secondary malignancies included various types of cancer. Kaplan-Meier survival analysis shows a difference suggesting that patients with a secondary malignancy demonstrate a worse survival compared to patients without a secondary tumor; no significance was detected (p = 0.349). Our data suggest that secondary malignancies in patients with NEN's especially in GEP-NENs are found more frequently than in general population. Therefore, patients with NEN need a continuous and detailed follow-up. The reason for the increased incidence of secondary malignancies in patients with NENs remains to be elucidated.