Neoadjuvant paclitaxel/olaparib in comparison to paclitaxel/carboplatinum in patients with HER2-negative breast cancer and homologous recombination deficiency (GeparOLA study).

BACKGROUND: The efficacy and toxicity of olaparib as combination therapy in early breast cancer (BC) patients with homologous recombinant deficiency (HRD) [score high and/or germline (g) or tumour (t) BRCA1/2 mutation] is not well described. GeparOLA (ClinicalTrials.gov, NCT02789332) investigated olaparib in combination with paclitaxel in HER2-negative early BC with HRD. PATIENTS AND METHODS: Patients with untreated primary HER2-negative cT2-cT4a-d or cT1c with either cN+ or pNSLN+ or cT1c and triple-negative breast cancer (TNBC) or cT1c and Ki-67>20% BC with HRD were randomised either to paclitaxel (P) 80 mg/m2 weekly plus olaparib (O) 100 mg twice daily for 12 weeks or P plus carboplatinum (Cb) area under the curve 2 weekly for 12 weeks, both followed by epirubicin/cyclophosphamide (EC). Stratification factors were hormone receptor (HR) status (HR+ versus HR-) and age (<40 versus ≥40 years). The primary endpoint was pathological complete response (pCR; ypT0/is ypN0). A two-sided one-group χ2-test was planned to exclude a pCR rate of ≤55% in the PO-EC arm. Secondary end points were other pCR definitions, breast conservation rate, clinical/imaging response, tolerability and safety. RESULTS: A total of 107 patients were randomised between September 2016 and July 2018; 106 (PO N = 69; PCb N = 37) started treatment. Median age was 47.0 years (range 25.0-71.0); 36.2% had cT1, 61.0% cT2, 2.9% cT3, and 31.8% cN-positive tumours; grade 3 tumours: 86.8%; Ki-67>20%: 89.6%; TNBC: 72.6%; confirmed gBRCA1/2 mutation: 56.2%. The pCR rate with PO was 55.1% [90% confidence interval (CI) 44.5% to 65.3%] versus PCb 48.6% (90% CI 34.3% to 63.2%). Analysis for the stratified subgroups showed higher pCR rates with PO in the cohorts of patients <40 years and HR+ patients. CONCLUSION: GeparOLA could not exclude a pCR rate of ≤55% in the PO arm. PO was significantly better tolerated and the combination merits further evaluation.

A randomised phase II study investigating durvalumab in addition to an anthracycline taxane-based neoadjuvant therapy in early triple-negative breast cancer: clinical results and biomarker analysis of GeparNuevo study.

BACKGROUND: Combining immune-checkpoint inhibitors with chemotherapy yielded an increased response rates in patients with metastatic triple-negative breast cancer (TNBC). Therefore, we evaluated the addition of durvalumab to standard neoadjuvant chemotherapy (NACT) in primary TNBC. PATIENTS AND METHODS: GeparNuevo is a randomised phase II double-blind placebo-controlled study randomising patients with TNBC to durvalumab or placebo given every 4 weeks in addition to nab-paclitaxel followed by standard EC. In the window-phase durvalumab/placebo alone was given 2 weeks before start of nab-paclitaxel. Randomisation was stratified by stromal tumour-infiltrating lymphocyte (sTILs). Patients with primary cT1b-cT4a-d disease, centrally confirmed TNBC and sTILs were included. Primary objective was pathological complete response (pCR) (ypT0 ypN0). RESULTS: A total of 174 patients were randomised, 117 participated in the window-phase. Median age was 49.5 years (range 23-76); 47 patients (27%) were younger than 40 years; 113 (65%) had stage ≥IIA disease, 25 (14%) high sTILs, 138 of 158 (87%) were PD-L1-positive. pCR rate with durvalumab was 53.4% (95% CI 42.5% to 61.4%) versus placebo 44.2% (95% CI 33.5% to 55.3%; unadjusted continuity corrected χ2P = 0.287), corresponding to OR = 1.45 (95% CI 0.80-2.63, unadjusted Wald P = 0.224). Durvalumab effect was seen only in the window cohort (pCR 61.0% versus 41.4%, OR = 2.22, 95% CI 1.06-4.64, P = 0.035; interaction P = 0.048). In both arms, significantly increased pCR (P < 0.01) were observed with higher sTILs. There was a trend for increased pCR rates in PD-L1-positive tumours, which was significant for PD-L1-tumour cell in durvalumab (P = 0.045) and for PD-L1-immune cell in placebo arm (P = 0.040). The most common immune-related adverse events were thyroid dysfunction any grade in 47%. CONCLUSIONS: Our results suggest that the addition of durvalumab to anthracycline-/taxane-based NACT increases pCR rate particularly in patients treated with durvalumab alone before start of chemotherapy. TRIAL REGISTRATION: ClinicalTrials.gov number: NCT02685059.

Expression of Cyclin D1 protein in residual tumor after neoadjuvant chemotherapy for breast cancer.

PURPOSE: Hormone receptor (HR)-positive breast cancer (BC) shows a poor response to neoadjuvant chemotherapy (NACT). New treatment targets like the Cyclin D1-CDK4/CDK6 complex are promising adjuvant/post-neoadjuvant therapeutic strategies. Evaluating Cyclin D1 overexpression in residual tumor could recognize those patients that benefit most from such post-neoadjuvant treatment. In this study, we determined Cyclin D1 expression in residual BC after NACT. Secondary aims were to correlate Cyclin D1 expression levels with clinicopathological parameters and to assess its prognostic value after NACT. METHODS: We retrospectively assessed the nuclear expression of Cyclin D1 on tissue microarrays with residual tumor from 284 patients treated in the neoadjuvant GeparTrio (n = 186) and GeparQuattro (n = 98) trials. Evaluation was performed with a standardized immunoreactive score (IRS) after selecting a cut-off value. RESULTS: A high expression level (IRS ≥ 6) of Cyclin D1 was found in 37.3% of the assessed specimens. An increased Cyclin D1 expression was observed in HR-positive tumors, compared to HR-negative tumors (p = 0.02). Low Cyclin D1 levels correlated with clinical tumor stage 1-3 (p = 0.03). Among patients with HR-positive/Her2-negative tumors and high Cyclin D1 expression, a better disease-free survival (DFS) was graphically suggested, but not significant (p = 0.21). CONCLUSION: Our study demonstrates a measurable nuclear expression of Cyclin D1 in post-neoadjuvant residual tumor tissue of HR-positive BC. Cyclin D1 expression was not prognostic for DFS after NACT. Our results and defined cut-off suggest that the marker can be used to stratify tumors according to protein expression levels. Based on this, a prospective evaluation is currently performed in the ongoing Penelope-B trial.

[Perioperative management of patients on NOACs]. / Perioperatives Management von Patienten unter NOAK.

Regarding thromboembolic events, non-vitamin K antagonists, so-called new oral anticoagulative agents (NOACs), have widely enlarged prophylaxis and therapy. In contrast to vitamin K antagonists they can be administered in a definite dose and do not need any regular control of coagulation parameters. Thus being simple in handling, these drugs have become enormously attractive for both patient and physician.In spite of all their advantages NOACs have to be considered carefully. They have a significant disadvantage: the plasma concentration is not detectable by a simple blood test, nor is there any antidote available. As a consequence the bleeding risk remains unknown.In this review we focus on two different settings in routine surgical work: the preoperative management of patients undergoing elective surgery differs significantly from that needed in urgent surgery.

Dual HER2-blockade with pertuzumab and trastuzumab in HER2-positive early breast cancer: a subanalysis of data from the randomized phase III GeparSepto trial.

Background: The neoadjuvant phase III GeparSepto study showed that substituting nab-paclitaxel for standard solvent-based paclitaxel significantly improved the pathologic complete response (pCR) rate achieved with a sequential neoadjuvant chemotherapy regimen of paclitaxel, epirubicin, and cyclophosphamide for high-risk primary breast cancer. Recent trials demonstrated that in HER2+ breast cancer pCR can be increased by using pertuzumab in addition to trastuzumab and chemotherapy. The present analysis focuses on efficacy and safety data from the subset of patients with HER2+ tumors from the GeparSepto trial (n = 396) in comparison to the HER2- cohort. Patients and methods: Patients with histologically confirmed breast cancer (n = 1206) received four cycles of weekly paclitaxel [either solvent-based (Pac) or nab-paclitaxel (nab-Pac), according to randomization] followed by 4 cycles of epirubicin 90 mg/m2 plus cyclophosphamide 600 mg/m2 q3w, with concurrent trastuzumab and pertuzumab q3w for those with HER2+ tumors. The primary endpoint was pCR defined as ypT0 ypN0. Results: Higher rates of pCR were achieved in HER2+ than in HER2- tumors (57.8% versus 22.0%, P < 0.0001), with the highest rate in the HER2+/HR- cohort (71.0%; 66.7% Pac, 74.6% nab-Pac). In HER2+/HR+ tumors, the pCR rate was 52.9% (49.7% Pac, 56.4% nab-Pac). Grade ≥3 toxic effects were significantly more common in HER2+ than in HER2- patients, with grade 3-4 diarrhea in 7.6% versus 0.9% (P < 0.001) and febrile neutropenia in 6.3% versus 3.3% (P = 0.023) of patients. Left ventricular ejection fraction decreases from baseline were uncommon, with 2.0% versus 0.4% of patients showing decreases to <50% along with a ≥10% decrease from baseline. Conclusion: In HER2+ early breast cancer, a dual HER2-targeted combination of pertuzumab and trastuzumab, together with taxane-epirubicin-cyclophosphamide neoadjuvant chemotherapy, achieved high rates of pCR.

Expression of secreted protein acidic and rich in cysteine (SPARC) in breast cancer and response to neoadjuvant chemotherapy.

BACKGROUND: Secreted protein acidic and rich in cysteine (SPARC) has been suggested as a new biomarker and therapeutic target in breast cancer, as well as other tumor types. PATIENTS AND METHODS: We evaluated the frequency of SPARC expression among different molecular breast cancer subtypes and its role for therapy response after neoadjuvant chemotherapy. In this study, pretherapeutic core biopsies of 667 patients from the neoadjuvant GeparTrio trial were evaluated for SPARC expression by immunohistochemistry using a standardized immunoreactive score (IRS). RESULTS: An increased SPARC expression (IRS ≥6) was observed in 26% of all tumors. In triple-negative tumors, SPARC expression was increased in 37% of tumors, compared with other molecular subtypes (23% HR+/HER2-, 29% HR+/HER2+ and 22% HR-/HER2+; P = 0.038). Increased SPARC expression was associated with an increased pathological complete response (pCR) rate of 27%, compared with 15% in tumors with low SPARC expression (P < 0.001). In the triple-negative subgroup, pCR rates were 47% in tumors with high SPARC expression, compared with 26% in tumors with low SPARC expression (P = 0.032). In multivariable analysis, SPARC was independently predictive in the overall population (P = 0.010) as well as the triple-negative subgroup (P = 0.036). CONCLUSIONS: SPARC is frequently expressed in breast cancer with triple-negative breast cancer revealing the highest expression rate. High SPARC expression of the primary tumor is associated with a higher chance of achieving a pathological complete remission after TAC or TAC-NX chemotherapy. As SPARC is an albumin-binding protein and might mediate intratumoral accumulation of albumin bound drugs, SPARC should be further evaluated as a predictive marker especially for response to albumin-bound drugs like nab-paclitaxel. CLINICAL TRIAL NUMBER: NCT00544765.

Molecular Markers as Prognostic Factors in DCIS and Small Invasive Breast Cancers.

Ductal carcinoma in situ (DCIS) accounts for up to half of screen-detected breast cancers and thus constitutes a major public health problem. Despite effective current treatment many patients with DCIS are either over- or undertreated because of the paucity of precise models to predict recurrence or progression. The combination of clinical and molecular factors as already applied for invasive disease may help to build such models also for DCIS. We compared 53 DCIS (36.6 %) and 92 (63.4 %) invasive breast cancer cases and found no significant differences in age, receptor status of ER, PR, and HER2, and the use of radiotherapy. Interestingly, the proportion of disseminated tumor cells (DTC) did also not significantly differ between DCIS and invasive cases (p = 0.57). A negative PR status was associated with the detection of DTCs (p = 0.026). We then compared relationships of clinical parameters and biomarkers with patients' prognosis in 43 DCIS and 40 small invasive tumors ≤ 5 mm (T1a). ER negativity was associated with shorter relapse free survival in the complete cohort (p = 0.004) and showed a trend in both subgroups (p = 0.053 for DCIS and p = 0.046 for T1a, respectively). In conclusion, we found markedly similar properties of both DCIS and small invasive breast cancers with respect to the distribution of several parameters as well as to the prognostic value of biomarkers. DCIS with a luminal phenotype seem to be characterized by a favourable prognosis.

The effect of intraarterial high-dose cisplatin on lymph nodes in oral and oropharyngeal cancer.

AIM OF STUDY: To assess the effect of strictly local treatment [intraarterial chemotherapy (iaCHT) with high-dose cisplatin and parallel neutralization] in the primary oral and oropharyngeal cancer (OOSCC) on the dependent cervical lymph nodes. PATIENTS AND METHODS: Seventeen consecutive patients with OOSCC and clinically positive necks underwent a prospective blinded comparison of two pre-surgical fluor18-deoxyglucose (FDG)-positron emission tomography (PET) examinations: baseline examination 1 week before and follow-up examination 3 weeks after iaCHT. Maximal standardized uptake (SUVmax) values of lymph nodes were measured and compared with each other and histopathology. RESULTS: The SUVmax value of the primary and all neck lymph nodes with uptake decreased significantly. Twelve/17 patients having metastases revealed significant decrease (P = 0.03), and benign lymph nodes showed non-significant decrease of the SUVmax. All neck lymph nodes with uptake and nodal metastases showed a significant reduction (P = 0.004) of standard uptake values (SUV). CONCLUSION: A regional effect of intraarterial cisplatin is proven. To date, it is not clear whether this is due to decreasing inflammatory reaction or a translymphatic anti-neoplastic effect.

Human herpesvirus 6 in biopsies from patients with gastrointestinal symptoms after allogeneic stem cell transplantation.

Gastrointestinal complications are frequent after allogeneic stem cell transplantation (allo-SCT). Main differential diagnoses are graft-versus-host disease (GvHD) and viral infections. In this retrospective analysis, we included 50 patients with severe vomiting or diarrhea in the first year after allo-SCT. One hundred two biopsies obtained by colonoscopy or endoscopy of the upper gastrointestinal tract were analysed by conventional histology for signs of GvHD and by qualitative polymerase chain reaction (PCR) for viral DNA of human herpesvirus 6 (HHV-6) and other virus of the herpes family. DNA of HHV-6 was detected in 38 of 75 initial samples (51%) and in 19 of 27 follow-up biopsies (70%). In the initial samples (n = 75), HHV-6 DNA was detected in 20/37 (54%) biopsies in the presence of GvHD compared to 18/38 (47%) biopsies without signs of GvHD. At the time of the first endoscopic investigation, most patients received antiviral prophylaxis with aciclovir. None of the follow-up biopsies was HHV-6 DNA negative after antiviral treatment with aciclovir, foscarnet or ganciclovir. By univariate analysis, no risk factor for HHV-6 detection could be demonstrated. In this cohort of patients with severe gastrointestinal complications, there was no significant difference in the overall survival between patients with or without HHV-6 DNA detection in the gastrointestinal tract. In summary, the detection of HHV-6 DNA had no impact on overall survival. Moreover, antiviral therapy against HHV-6 was without effect. Thus, positive PCR results in GI tract samples do not necessarily reflect reactivation of HHV-6. Further studies are needed to define the significance of HHV-6 for GI tract symptoms after allo-SCT.

Trends in the postmortem epidemiology of invasive fungal infections at a university hospital.

BACKGROUND: Due to the continuing lack of sensitive and specific diagnostic tools, clinical data on opportunistic invasive fungal infections (IFIs) remain difficult to assess and postmortem data are indispensable to monitor trends in frequency and disease patterns. METHODS: Following-up on our previous report covering the period between 1978 and 1992, all protocols of postmortems performed between 1993 and 2005 at the University Hospital of Frankfurt/Main were retrospectively screened for the presence of IFIs. RESULTS: The analysis of 2707 consecutive autopsies identified 221 patients with IFIs (mean age, 52 years; range, 10 days-94 years). The prevalence of IFIs at autopsy steadily increased over the analyzed time periods (from 6.6% in 1993-1996 to 10.4% in 2001-2005), continuing the trend that was observed at our institution before. The increasing prevalence of IFIs was mainly due to an increase in Candida infections; rates of infections caused by Aspergillus, Cryptococcus, Zygomycetes and Pneumocystis remained constant. However, Aspergillus remained the leading pathogen. Patients with hematologic malignancies had the highest frequency of IFIs at postmortem. Candida most commonly affected the gastrointestinal tract, whereas Aspergillus most commonly affected the lung. CONCLUSIONS: The results of this analysis show continuing and relevant changes in the epidemiology of IFIs over time. Despite the expanding antifungal armamentarium, IFIs infections remain an important cause of morbidity and mortality in severely ill hospitalized patients.

Efficacy and safety of sorafenib in advanced hepatocellular carcinoma under daily practice conditions.

Sorafenib has recently been shown to be effective for the treatment of advanced hepatocellular carcinoma in randomized controlled trials. Here, we report the experience with sorafenib in 25 patients with advanced HCC under daily practice conditions. Tolerance to sorafenib was acceptable and side effects were manageable, although the ECOG performance status was reduced in all patients. The most prevalent grade 2/3 side effects were fatigue (40%) and diarrhea (24%), and withdrawal from therapy occurred in 29% of patients. Disease stabilization was documented in 60% of patients. The median treatment time was 2.7 months and overall survival was 11.0 months. No significant serum alpha-fetoprotein decline was noted at the time of the first radiological control in a subgroup of patients with baseline levels >50 ng/ml who achieved stable disease. In conclusion, in daily practice sorafenib is safe and disease stabilization can be achieved in the majority of patients. However, intolerance to sorafenib can affect treatment adherence substantially.

Clinical relevance of the putative stem cell marker p63 in breast cancer.

P63 is a member of the p53 family. This protein is crucial for the maintenance of a stem cell population in the human epithelium and necessary for the normal development of all epithelial tissues including mammary glands. In normal breast tissue, the p63 seems to be a specific myoepithelial cell marker. P63 expression has been described in highly aggressive ER negative basal-like breast tumors. The value of p63 expression in ER positive disease is less clear. The expression levels of p63 mRNA by Affymetrix microarray analysis in a combined cohort of 2,158 ER positive breast cancers and its prognostic and predictive impact were analyzed. Tumor samples containing large amounts of benign breast tissue, which will interfere with p63 measurement, were excluded prior to the analysis. Survival analysis revealed a better prognosis of ER positive breast cancer expressing p63 (n = 410; P < 0.036). No correlation of p63 with standard parameters was observed. In a subgroup analysis, endocrine-treated patients with high p63 expression showed a better prognosis than low p63 expression (P = 0.06; n = 186). In untreated patients, this effect was less clear (n = 148; P = 0.5). P63 is a positive prognostic factor in endocrine-treated ER positive breast cancer and might influence responsiveness to endocrine treatment. Thus, p63 could be helpful as a predictive factor for endocrine therapy.

Prognostic impact of thymidine phosphorylase expression in breast cancer--comparison of microarray and immunohistochemical data.

Contrary findings exist according to the prognostic and predictive impact of thymidine phosphorylase (TP) expression in breast cancer. Goal of our study was to investigate TP expression on the mRNA level by microarray analysis in a large cohort of 1781 breast cancers and to analyse its prognostic impact. Furthermore we compared mRNA expression and immunohistochemical data to explain discrepancies between different studies. The prognostic value of TP mRNA expression was analysed among n=622 untreated patients. Strong expression in the subgroup of n=213 ER-negative cancer correlates with improved survival (P=0.012). In contrast, no difference in survival was detected in the ER-positive group. We also failed to observe a prognostic value of TP mRNA among n=435 endocrine-treated patients as well as n=111 CMF-treated patients. In an unsupervised analysis, TP clustered together with genes expressed in immune cells. Moreover, among normal tissues the highest TP mRNA expression was found in tissues of the immune system. The profile of TP expression in breast cancers correlates to a metagene of interferon induction whereas the expression of TP among normal tissues correlates to a metagene for macrophages. When comparing microarray data with immunohistochemistry from the same n=51 samples, there was no correlation with stained carcinoma cells. In contrast, the correlation with stromal staining was highly significant (P<0.001). Thus TP mRNA from microarray mainly reflects expression in stromal and immune cells. This could account for discrepant results from mRNA and IHC studies. In conclusion, the tumour infiltrating immune cells seem to be a major source of TP expression and predict a favourable prognosis in ER-negative breast cancer. Our data point to a role of TP in host immune response.

Acid ceramidase 1 expression correlates with a better prognosis in ER-positive breast cancer.

OBJECTIVES: Ceramide and sphingosine mediate response to cancer therapy, inhibit cell growth and induce apoptosis in vitro. Only a few clinical data about the impact of ceramide and sphingosine iny vivo are available. We investigated the relevance of ceramide- and sphingosine-generating enzymes in breast cancer (acid ceramidase 1 (ASAH1), ceramide synthases 4 (LASS4) and 6 (LASS6)) by means of gene expression analysis. METHODS: We analyzed differences in ASAH1, LASS4 and LASS6 on mRNA level between breast cancer subgroups using microarray data from 1581 tumor samples. RESULTS: High ASAH1, LASS4 and LASS6 expression correlates with pathohistological grading (p < 0.001) and estrogen receptor (ER) status (p < 0.001). High ASAH1 expression was associated with a larger tumor size >2 cm (p = 0.003), while high LASS6 expression was correlated with ErbB2 negativity (p < 0.001). In survival analysis, we detected a significant better prognosis of patients with higher ASAH1 expression (p = 0.002) in the ER-positive subgroup. In contrast, expression of LASS4 or LASS6 did not show any prognostic impact. In the multivariate analysis, only ASAH1 expression (p = 0.002), tumor size (p < 0.0001) and ErbB2 positivity (p = 0.041) remained significant. CONCLUSION: ASAH1 is an estrogen-dependent member of the sphingolipid metabolism, which might provide further prognostic information in ER-positive breast cancers.

Lymphoplasmacytic lymphoma with Waldenstrom's macroglobulinemia as a reason for peripheral arterial perfusion disorders.

Peripheral arterial perfusion disorders are often caused by embolism and thrombosis induced by diseases of the cardiovascular system. We report about a case of a 42-year-old female with peripheral arterial perfusion disturbances of the digital arteries caused by Waldenstrom s disease due to high plasma viscosity. Our patient presented with elevated plasma viscosity (1.34 mPA) and therefore plasmapheresis was necessary. Plasma separation is the most effective acute treatment for symptomatic hyperviscosity syndrome. In a second step patients with clinical symptoms of M. Waldenstrom have to be treated by chemotherapy.

VEGF-A and i-NOS expression are prognostic factors in serous epithelial ovarian carcinomas after complete surgical resection.

AIMS: Clinical stage at the time of diagnosis and achievement of complete macroscopic resection during initial surgery are key factors determining the outcome of ovarian cancer. However, prediction of outcome lacks accuracy and more reliable prognostic factors are required. Therefore, an analysis and evaluation of key angiogenic factors was carried out to determine their diagnostic and prognostic value in serous ovarian cancer. METHODS: Expression levels of vascular endothelial growth factor (VEGF)-A, hypoxia-inducible factor (HIF)1-alpha and inducible nitric oxide synthase (i-NOS) were analysed by immunohistochemistry in a homogenous group of 112 patients with serous adenocarcinoma of the ovary. Vascular density as an indicator of angiogenesis was assessed using the Chalkley eyepiece method after staining for CD34. The correlation of these data with survival and established prognostic factors such as histological grade, Federation of Gynecology and Obstetrics (FIGO) stage, and residual tumour after surgery, was evaluated. Survival analyses, multivariate analyses and correlation tests were performed. RESULTS: In the patient group with macroscopic complete tumour resection (R0) there was a significant correlation between VEGF-A and i-NOS expression. Kaplan-Meier analysis further revealed improved progression-free survival for R0 patients with VEGF-A-positive and i-NOS-negative tumours. The predictive relevance of VEGF-A regarding progression-free survival was sustained in multivariate analysis using FIGO stage, grading and resection status as fixed variables. CONCLUSION: VEGF-A and i-NOS are prognostic markers for clinical outcome in serous ovarian cancer patients with macroscopic complete tumour resection (R0). Hence, pre-therapeutic assessment of VEGF-A as predictive factor for an antiangiogenic therapy might be of clinical value.

Neoadjuvant treatment with cetuximab, 5-Fluorouracil, folinic Acid and oxaliplatin in unresectable retroperitoneal recurrent colon cancer.

Some patients with initially unresectable hepatic colorectal cancer metastases can be effectively treated with neoadjuvant chemotherapy to allow operative resection in curative intent. Here, we report on a patient with unresectable locoregional recurrence of colon cancer, which was down-staged using combination chemotherapy with infusional 5-fluorouracil, folinic acid, oxaliplatin and cetuximab. After 12 weeks of therapy a partial response was documented and 3 weeks later the tumor was completely resected without increased perioperative morbidity. Therefore, neoadjuvant treatment with molecular targeted agents in combination with chemotherapy can also be an option to enable selected patients with locoregional recurrence to undergo surgical resection in curative intent.

Prognostic relevance of volumetric analysis in tumour specimens of hypopharyngeal cancer.

OBJECTIVE: The purpose of this study was to investigate the prognostic relevance of the tumour specimen's volume in patients with squamous cell cancers of the hypopharynx. DESIGN: Tumour specimens of 67 patients treated primarily with surgery were evaluated, prospectively. Pathologic tumour volume was described as the product of the three longest diameters of the tumour in cubic millimeters (mm(3)). Statistical analysis was performed to determine the relation of pathologic tumour volume to pTNM stages as well as to patients' survival. This study has been approved by our institutional review board. RESULTS: Pathologic tumour volume was significantly associated with pT (P = 0.006) and pN (P = 0.01). The univariate evaluation of tumour variables showed pathologic tumour volume (P = 0.01) and pN (P = 0.04) as the only parameters which were significantly associated with overall survival. Entering these variables in a Cox regression model, pathologic tumour volume had the most impact on overall survival (P = 0.03). Most important thereby is the fact that we could distinguish within the pN0 group between the more and the less favourable cases. CONCLUSION: Pathologic tumour volume could be an essential prognostic indicator and the inclusion of this parameter in future clinical trials is recommended.

[Subcutaneous emphysema of unusual extent]. / Weichteilemphysem ungewöhnlichen Ausmasses.

Streptococcus agalactiae, known as a pathogen that causes meningitis and septicemia in neonates, emerges as an invasive organism in nonpregnant adults. This case report describes the fulminant course of a necrotizing fasciitis (NF) with streptococcal toxic shock-like syndrome (STSS) in a 76-year-old diabetic patient caused by S. agalactiae, serotype V. Chronic diseases and immunodeficiency are considered to be risk factors for the acquisition of group B streptococcal disease. Since early surgical treatment in conjunction with antimicrobial and intensive care therapy is critical for the outcome of patients with NF and/or STSS, clinicians should be aware of invasive S. agalactiae infections in adults with subcutaneous emphysema.