In the setting of isolated limb perfusion, TNF is an active anticancer drug in patients. The ILP with TNF + melphalan can be performed safely in many centers and is an effective induction treatment with a high response rate that can achieve limb salvage in patients with locally advanced extremity soft tissue sarcoma.

Regulatory T cells (T reg ) inhibit the generation of host-versus-tumor immunity via suppression of tumor-specific effector T-cell responses and development of immune tolerance to neoplastic cells. The transcription factor forkhead box P3 (FOXP3) is an intracellular key molecule for T reg development and function and is considered to represent the most specific T reg cell marker. Tumor-infiltrating lymphocytes (TILs) are considered to be the primary host immune response against solid tumors. Recent results have shown a correlation between survival and density of TILs in colorectal cancer (CRC) patients. 1 Furthermore, there is accumulating evidence that the type of immune cells, rather than their sheer quantity, controls the efficiency of the host-versus-tumor immune response.2 However, the role of TILs in predicting CRC prognosis remains a matter of ongoing debate. Controversy may arise from the uncertainty concerning the in vivo activity of TILs as well as from the lack of discriminating patients according to the underlying type of genomic instability (microsatellite stable vs. unstable). Approximately 10-15% of sporadic CRC and all cases with hereditary nonpolyposis colorectal cancer (HNPCC) are associated with high frequency of microsatellite instability as a result of inactivation or loss of expression of the mismatch repair (MMR) genes MLH1, MSH2 and MSH6 (so-called MMR-deficient tumors). Compared to the majority of sporadic CRC that are MMR-proficient tumors, MMR-deficient tumors are characterized a priori by a higher frequency of TILs and are associated with significantly improved prognosis. 3 Increasing evidence suggests that regulatory T cells (T reg ) have the ability to inhibit the generation of host-versustumor immunity in the microenvironment of tumors via suppression of tumor-specific effector T-cell responses.4,5 The transcription factor forkhead box P3 (FOXP3) is an intracellular key molecule for T reg development and function and is considered to represent the most specific T reg cell marker so far. [6][7][8] In the majority of solid tumors studied so far, high frequency of tumor-infiltrating FOXP3 þ T reg predicted an impaired patient survival. [7][8][9][10][11][12][13][14][15][16] Paradoxically, increased frequency of T reg was recently found to be associated with improved prognosis in lymphoma patients 17 and also in CRC

Melanoma is a malignant tumor that arises from melanocytic cells and primarily involves the skin. The most important exogenous etiological factor is exposure to ultraviolet irradiation. Diagnosis of melanoma is based primarily on its clinical features, and the A-B-C-D rule is useful in identifying pigmented lesions, which are suspicious for melanoma (Asymmetry, Border irregular, Color inhomogeneous and Diameter more than 5 mm). Dermoscopy is very helpful in clarifying the differential diagnosis of pigmented lesions. About 90% of melanomas are diagnosed as primary tumors without any evidence for metastasis. The tumor-specific 10-year survival for all such tumors is about 75-85%. The most important prognostic factors for primary melanoma without metastases are vertical tumor thickness (Breslow depth) as measured on the histological specimen, presence of histopathologically recognized ulceration, invasion level (Clark level) and identification of micrometastases in the regional lymph nodes via sentinel lymph node biopsy. The current tumor node metastasis classification for the staging of primary melanoma is based on these factors. Melanomas can metastasize either by the lymphatic or by the hematogenous route. About two-thirds of metastases are originally confined to the drainage area of regional lymph nodes. A regional metastasis can appear as satellite metastases up to 2 cm from the primary tumor, as intransit metastases in the skin between the site of the primary tumor and the first lymph node and as regional lymph node metastases. In the stage of regional metastasis, the differentiation between micrometastasis and macrometastasis and the number of lymph nodes involved are crucial. As soon as distant metastasis develops, prognosis depends on the site of the metastasis and on the lactate dehydrogenase levels in the blood. The frequency and extent of follow-up examinations is based on the initial tumor parameters. In thin primary melanomas up to 1-mm tumor thickness, clinical examinations at 6-month intervals are sufficient and in thicker primary melanomas, at 3-month intervals. Lymph node sonography as well as determination of the tumor marker protein S100beta are recommended. Additionally, in the stage of regional metastasis, whole body imaging should be performed every 6 months; in the stage of distant metastasis, surveillance has to be scheduled individually.

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Background: Enhanced recovery after surgery (ERAS) or fast-track surgery is a perioperative and postoperative care concept initiated in the early 1990s aiming to reduce the length of hospital stays following elective abdominal surgery. Twenty treatment items defined in the Consensus Guidelines established in 2009 were included in this concept. The success of ERAS depends highly on multidisciplinary teamwork and patient compliance. Several ERAS items and their impact on perioperative and postoperative care have recently been discussed. In this connection, translational research topics triggered increasing interest in ERAS and new impulses aimed at improving the ERAS concept. We thus reviewed the surgical literature to highlight the role of translational research items in ERAS. Methods: A literature search of Medline®, PubMed® and the Cochrane Database was performed. Two investigators independently reviewed the abstracts and appropriate articles were included in this review. Results: Articles have been selected. The advantages of the ERAS concept over conventional postoperative care were established by four meta-analyses and several reviews. But, due to the lack of standardization of the protocols, the level of evidence is still low. The implementation of ERAS into clinical practice is furthermore hampered by the poor compliance with ERAS protocols and remains a challenge for the future. Moreover, recent trials challenge the role of some ERAS items, e.g. epidural anesthesia. Translational research trials investigating stress, immune and inflammatory response after surgery, new analgesic concepts, goal-directed fluid therapy and new drugs and substances to improve the outcome of ERAS provide first promising data but still need to be integrated in the ERAS concept. Conclusion: The Consensus Guidelines for ERAS are subject to the constant evolution of treatment strategies and implementation of translational research findings. Improvement of the compliance with ERAS protocols in surgical clinics and updating of ERAS items taking into account recent findings in translational research may improve the outcomes of ERAS but remain a long-term challenge in surgery for the next years.

BackgroundIt remains a matter of debate whether colorectal cancer resection in an emergency setting negatively impacts on survival. Our objective was therefore to assess the impact of urgent versus elective operation on overall and disease-free survival in patients undergoing resection for colorectal cancer by using propensity score adjusted analysis.MethodsIn a single-center study patients operated for colorectal cancer between 1989 and 2013 were identified from a prospectively maintained database. Median follow-up was 44 months. Patients with neoadjuvant treatment were excluded. The impact of urgent operation on overall and disease-free survival was assessed using both Cox regression and propensity score analyses.ResultsOf 747 patients with colorectal cancer, 84 (11 %) had urgent and 663 elective cancer resection. The propensity score revealed strongly biased patient characteristics (0.22 ± 0.16 vs. 0.10 ± 0.09; P < 0.001). In unadjusted analysis urgent operation was associated with a 35 % increased risk of overall mortality (hazard ratio(HR) of death = 1.35, 95 % confidence interval(CI):1.02–1.78, P = 0.045). In risk-adjusted Cox regression analysis urgent operation was not associated with poor overall (HR = 1.08, 95 %CI:0.79–1.48; P = 0.629) or disease-free survival (HR = 1.02, 95 %CI:0.76–1.38; P = 0.877). Similarly in propensity score analysis urgent operation did not influence overall (HR = 0.98, 95 % CI:0.74–1.29), P = 0.872) and disease-free survival (HR = 0.89, 95 %CI:0.68 to 1.16, P = 0.387).ConclusionsThis study provides evidence that worse oncologic outcomes after urgent operation for colorectal cancer are caused by clinical circumstances and not due to the urgent operation itself. Urgent operation is not a risk factor for colorectal cancer resection.

Background The implementation of intraoperative navigation in liver surgery is handicapped by intraoperative organ shift, tissue deformation, the absence of external landmarks, and anatomical differences in the vascular tree. To investigate the impact of surgical manipulation on the liver surface and intrahepatic structures, we conducted a prospective clinical trial. Methods Eleven consecutive patients [4 female and 7 male, median age = 67 years (range = 54-80)] with malignant liver disease [colorectal metastasis (n = 9) and hepatocellular cancer (n = 2)] underwent hepatic resection. Pre-and intraoperatively, all patients were studied by CT-based 3D imaging and assessed for the potential value of computer-assisted planning. The degree of liver deformation was demonstrated by comparing pre-and intraoperative imaging. Results Intraoperative CT imaging was successful in all patients. We found significant deformation of the liver. The deformation of the segmental structures is reflected by the observed variation of the displacements. There is no rigid alignment of the pre-and intraoperative organ positions due to overall deflection of the liver. Locally, a rigid alignment of the anatomical structure can be achieved with less than 0.5 cm discrepancy relative to a segmental unit of the liver. Changes in total liver volume range from -13 to ?24%, with an average absolute difference of 7%. Conclusions These findings are fundamental for further development and optimization of intraoperative navigation in liver surgery. In particular, these data will play an important role in developing automation of intraoperative continuous registration. This automation compensates for liver shift during surgery and permits real-time 3D visualization of navigation imaging.

The primary treatment of a melanoma is surgical excision. An excisional biopsy is preferred, and safety margins of 1 cm for tumor thickness up to 2 mm and 2 cm for higher tumor thickness should be applied either at primary excision or in a two-step procedure. When dealing with facial, acral or anogenital melanomas, micrographic control of the surgical margins may be preferable to allow reduced safety margins and conservation of tissue. The sentinel lymph node biopsy should be performed in patients whose primary melanoma is thicker than 1.0 mm and this operation should be performed in centers where both the operative and nuclear medicine teams are experienced. In clinically identified lymph node metastases, radical lymph node dissection is considered standard therapy. If distant metastases involve just one internal organ and operative removal is feasible, then surgery should be seen as therapy of choice. Radiation therapy for the primary treatment of melanoma is indicated only in those cases in which surgery is impossible or not reasonable. In regional lymph nodes, radiation therapy is usually recommended when excision is not complete (R1 resection) or if the nodes are inoperable. In distant metastases, radiation therapy is particularly indicated in bone metastases, brain metastases and soft tissue metastases.