Serum procalcitonin improves diagnosis of infectious complications after CRS/HIPEC.

BACKGROUND: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) improve the survival of selected patients with peritoneal metastasis. A major cause of treatment-related morbidity after CRS/HIPEC is infection and sepsis. HIPEC alters the diagnostic sensitivity and specificity of blood and serum markers and therefore has an impact on early diagnosis of postoperative complications. This study aimed to assess the sensitivity and specificity of blood and serum markers after CRS/HIPEC. METHODS: Patients from two centers, operated between 2009 and 2017, were enrolled in this study. Perioperative blood samples were analyzed for white blood cells (WBC), C-reactive protein (CRP), and procalcitonin (PCT); postoperative complications were graded according to Clavien-Dindo and infectious complications according to CDC criteria. RESULTS: Overall, n=248 patients were included with peritoneal metastasis from different primary tumors treated by CRS/HIPEC. Depending on the applied HIPEC protocol, patients presented a suppressed WBC response to infection. In addition, a secondary and unspecific CRP elevation in absence of an underlining infection, and pronounced after prolonged perfusion for more than 60 min. PCT was identified as a highly specific - although less sensitive - marker to diagnose infectious complications after CRS/HIPEC. DISCUSSION/CONCLUSION: Sensitivity and specificity of WBC counts and CRP values to diagnose postoperative infection are limited in the context of HIPEC. PCT is helpful to specify suspected infection. Overall, diagnosis of postoperative complications remains a clinical diagnosis, requiring surgical expertise and experience.

Primary External Stenting of an Autogenous Brachial-Basilic Upper Arm Transposition.

High-volume shunt flow after arteriovenous fistula (AVF) creation for hemodialysis can cause high-output heart failure. We used the Frame™ (Vascular Graft Solutions Ltd., Tel Aviv, Israel) external support, a stent, to limit vein dilatation and consecutive high-volume shunt in a 62-old female who underwent brachial-basilic upper arm transposition. After maturation, the shunt was used for dialysis and showed a plateauing flow volume 3 months after the operation. This case illustrates the safety and feasibility of this intervention when performed during AVF formation.

Preoperative ultrasound improves patency and cost effectiveness in arteriovenous fistula surgery.

OBJECTIVE: We aimed to compare routine preoperative color-coded duplex ultrasound (DUS) to clinical examination (CE) alone in surgery for arteriovenous fistula (AVF) with special emphasis on long-term outcomes and cost effectiveness. METHODS: All patients undergoing an AVF formation or revision between January 1, 2011, and December 31, 2016, at our tertiary referral center were subject to analysis. Routine DUS was performed in 114 patients and CE alone in 217 patients. Primary and secondary patency, the need for revision or reintervention to obtain patency, and individual as well as overall costs were analyzed. RESULTS: Primary patency rate was higher in AVF after DUS compared with CE alone at 62% vs 26% (P < .05), respectively. Patients receiving DUS had significantly lower rates of revision and revisions per patient when compared with CE (25.4% vs 59.4% [P < .0001]; 0.36 ± 0.71 vs 1.06 ± 1.55 [P < .0001], respectively). Costs per patient were significantly lower in the DUS group compared with CE at 4074€ vs 6078€ (P < .0001). CONCLUSIONS: We were able to show that patients receiving preoperative DUS showed higher patency rates and needed fewer revisions. Standard preoperative ultrasound examination is an easy tool to improve outcomes and cost effectiveness in AVF surgery.

Mutations of RAS/RAF Proto-oncogenes Impair Survival After Cytoreductive Surgery and HIPEC for Peritoneal Metastasis of Colorectal Origin.

BACKGROUND: Adequate selection of patients with peritoneal metastasis (PM) for cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) remains critical for successful long-term outcomes. Factors reflecting tumor biology are currently poorly represented in the selection process. The prognostic relevance of RAS/RAF mutations in patients with PM remains unclear. METHODS: Survival data of patients with colorectal PM operated in 6 European tertiary centers were retrospectively collected and predictive factors for survival identified by Cox regression analyses. A simple point-based risk score was developed to allow patient selection and outcome prediction. RESULTS: Data of 524 patients with a median age of 59 years and a median peritoneal cancer index of 7 (interquartile range: 3-12) were collected. A complete resection was possible in 505 patients; overall morbidity and 90-day mortality were 50.9% and 2.1%, respectively. PCI [hazard ratio (HR): 1.08], N1 stage (HR: 2.15), N2 stage (HR: 2.57), G3 stage (HR: 1.80) as well as KRAS (HR: 1.46) and BRAF (HR: 3.97) mutations were found to significantly impair survival after CRS/HIPEC on multivariate analyses. Mutations of RAS/RAF impaired survival independently of targeted treatment against EGFR. Consequently, a simple point-based risk score termed BIOSCOPE (BIOlogical Score of COlorectal PEritoneal metastasis) based on PCI, N-, G-, and RAS/RAF status was developed, which showed good discrimination [development area under the curve (AUC) = 0.72, validation AUC = 0.70], calibration (P = 0.401) and allowed categorization of patients into 4 groups with strongly divergent survival outcomes. CONCLUSION: RAS/RAF mutations impair survival after CRS/HIPEC. The novel BIOSCOPE score reflects tumor biology, adequately stratifies long-term outcomes, and improves patient assessment and selection.

NephroCheck data compared to serum creatinine in various clinical settings.

BACKGROUND: Acute kidney injury is frequently observed at the intensive care unit, after surgery, and after toxic drug administration. A rise in serum creatinine and a fall in urine output are consequences of much earlier injury to the most sensitive part of tubular cells located at the proximal tubule. The aim of the present study was to investigate the course of two cell-cycle arrest urinary biomarkers compared to serum creatinine in four clinical settings: ischemic reperfusion injury, cardiac failure, severe acute kidney injury, and chemotherapy-induced kidney injury. METHODS: A recently developed bedside test known as NephroCheck measures two urinary parameters: insulin-like growth factor binding protein 7 (IGFBP7) and tissue inhibitor of metalloproteinase-2 (TIMP-2). The test is based on a sandwich immunoassay technique. The final test output, labeled AKIRisk, is shown as a numeric result. RESULTS: This report revealed that [IGFBP7] · [TIMP-2] in urine rise rapidly prior to any change in serum creatinine. A unique feature of all four clinical settings is that a rapid decline predicts the recovery of kidney function. Besides, a subclinical kidney injury might be detected by the test. CONCLUSION: This bedside test detects biomarkers of renal injury. A rapid decline in AKIRisk was associated with the restoration of kidney function, whereas a prolonged high AKIRisk score was associated with end-stage renal disease. However, the dynamics seem to differ, depending on the cause and the extent of injury. Further studies will be needed to clarify the issue.

Certified Fellowship in Abdominal Wall Surgery-A Collaboration Between the UEMS and the European Hernia Society.

Background: Abdominal wall surgery (AWS) is characterised by the increasing caseload and the complexity of the surgical procedures. The introduction of a tailored approach to AWS utilising laparoendoscopic, robotic and/or open techniques requires the surgeon to master several surgical techniques. All of which have an associated learning curve, and the necessary knowledge/experience to know which operation is the right one for the individual patient. However, the reality in general surgery training shows that training in just a limited number of procedures is not enough. By the end of general surgery training, many chief residents do not feel they are yet ready to carry out surgery independently. Therefore, hernia surgery experts and societies have called for the introduction of a Fellowship in Abdominal Wall Surgery. Methods: The UEMS (Union Européenne des Médecins Spécialistes, European Union of Medical Specialists) in collaboration with the European Hernia Society (EHS) introduced a fellowship by examination in 2019. As a prerequisite, candidates must complete further training of at least 2 years with a special focus on abdominal wall surgery after having completed their training in general surgery. To be eligible for the examination, candidates must provide evidence of having performed 300 hernia procedures. In addition, candidates must have accrued sufficient "knowledge points" by attending abdominal wall surgery congresses, courses and clinical visitations, and engaged in scientific activities. On meeting the requirements, a candidate may be admitted to the written and oral examination. Results: To date, three examinations have been held on the occasion of the Annual Congress of the European Hernia Society in Copenhagen (2021), Manchester (2022) and Barcelona (2023). Having met the requirements, 48 surgeons passed the written and oral examination and were awarded the Fellow European Board of Surgery-Abdominal Wall Surgery certificate. During this time period, a further 25 surgeons applied to sit the examination but did not fulfil all the criteria to be eligible for the examination. Fifty experienced abdominal wall surgeons applied to become an Honorary Fellow European Board of Surgery-Abdominal Wall Surgery. Fourty eight were successful in their application. Conclusion: The Fellowship of the European Board of Surgery - Abdominal Wall Surgery by examination has been successfully introduced at European level by the joint work of the UEMS and the EHS. The examination is also open to surgeons who work outside the European area, if they can fulfil the eligibility criteria.

Neoadjuvant treatment of colorectal cancer with bevacizumab: the perioperative angiogenic balance is sensitive to systemic thrombospondin-1 levels.

PURPOSE: Colorectal cancer patients receiving neoadjuvant treatment with bevacizumab, a monoclonal antibody neutralizing vascular endothelial growth factor (VEGF), may suffer from wound healing complications after surgery as the antibody persists in patient blood. We characterized the systemic angiogenic balance in the perioperative period to evaluate its effect on physiologic angiogenesis. EXPERIMENTAL DESIGN: Nineteen patients receiving combination chemotherapy and bevacizumab for six neoadjuvant cycles were compared with 14 patients receiving chemotherapy without bevacizumab. Plasma from perioperative days -1, +1, +7, and +21 was analyzed for VEGF, thrombospondin-1 (TSP-1), and PD-ECGF concentrations. The angiogenic capacity was further tested in an in vitro assay of endothelial cell proliferation and migration. RESULTS: On day +1, the onset of wound healing was reflected in a change of balance, i.e., an increase of proangiogenic factors VEGF and platelet-derived endothelial cell growth factor compared with low TSP-1 inhibitor levels in both treatment groups. Patients with bevacizumab therapy showed significantly higher blood levels of total VEGF throughout the evaluation period. However, most VEGF molecules were inactive, i.e., complexed with antibody. Nevertheless, the capacity to stimulate endothelial growth was higher for these plasma samples and was reflected in low TSP-1 levels and an altered TSP-1 sensitivity. When purified TSP-1 protein was added, plasma samples of the bevacizumab but not the chemotherapy group showed reduced endothelial growth. CONCLUSIONS: Feedback mechanisms of bevacizumab therapy are not restricted to VEGF expression but seem to involve additional factors, such as TSP-1, which influences the systemic angiogenic balance and permits endothelial growth.

Systemic inflammatory response after hyperthermic intraperitoneal chemotherapy (HIPEC): The perfusion protocol matters!

BACKGROUND: CRS/HIPEC gained acceptance as a treatment for selected patients with peritoneal metastasis. However, the pathophysiology behind HIPEC is poorly understood, and a variety of regimens are currently in use. In this study, we describe for the first-time changes in the postoperative systemic inflammatory reaction, highly different among HIPEC treatment protocols. METHODS: HIPEC was performed with three protocols, different with regard to perfusion times and drugs: (mitomycinC/doxorubicin, 90min), (cisplatin, 90min) (oxaliplatin, 30min). Serial blood samples were assessed for C-reactive protein (CRP), white blood cells (WBC), pancreatic stone protein (PSP) and bacterial component (16s rDNA). The study was approved by the local ethics committee and registered at clinicaltirals.gov (NCT02741167). RESULTS: Overall, 140 patients from two European centers were included. In patients without postoperative complications, a secondary peak of inflammatory parameters, CRP (p = 0.015) and PSP (p = 0.004) was observed after HIPEC for 90 min with mitomycinC/doxorubicin or cisplatin but not after 30 min oxaliplatin. In patients after 90 min HIPEC, postoperative serum bacterial 16srDNA level were 2.1 times higher (95% CI 0.646-3.032, p = 0.015) compared to 30 min oxaliplatin. DISCUSSION: In conclusion, we identified a secondary inflammatory reaction after 90 min HIPEC, either with mitomycinC/doxorubicin or cisplatin, not observed after short course HIPEC with oxaliplatin. This protocol dependent physiology of acute phase proteins should be known in the clinical management of patients after HIPEC.

Sentinel lymph node biopsy after preoperative chemotherapy for breast cancer: findings from the Austrian Sentinel Node Study Group.

BACKGROUND: Sentinel lymph node biopsy (SLNB) has become an accurate alternative to axillary lymph node dissection for early breast cancer. However, data are still insufficient as regards the combination of SLNB with preoperative chemotherapy (PC). METHODS: The Austrian Sentinel Node Study Group investigated 167 patients who underwent SLNB and axillary lymph node dissection after 3 to 6 courses of PC. SLNB was limited to patients with a clinically negative axilla after PC. Blue dye was used in 29 cases (17%), and tracers were used in 20 (12%). A combination of the two methods was applied in most patients (n = 120; 72%). RESULTS: At least 1 sentinel lymph node (SLN) was identified in 144 patients (identification rate, 85%): in 86% by blue dye alone, in 65% by tracers alone, and in 88% by a combination of methods. The SLN was positive in 70 women (42%) and was the only positive node with otherwise negative axillary nodes in 39 patients (23%). In 6 cases, the SLN was diagnosed as negative although tumor infiltration was detected in an upper node of the axillary basin (false-negative rate, 8%; 6 of 76 patients; sensitivity, 92%). At least 62 patients (37%) were free of tumor cells in the SLN and in the axillary nodes. CONCLUSION: The results of SLNB after PC are comparable to the results of SLNB without PC. Further investigation in a prospective setting is warranted to confirm these promising results.

A nonrandomized follow-up comparison between standard axillary node dissection and sentinel node biopsy in breast cancer.

INTRODUCTION: In many countries sentinel node biopsy (SNB) has become the standard of care in breast cancer based on a large number of observational studies but without results from prospective randomized trials. The goal of our study was to evaluate the oncological safety of the SNB in breast cancer in a multicenter, nonrandomized setting with comparable groups. PATIENTS AND METHODS: Between 1996/05 and 2004/11, 2942 patients from 14 departments in Austria with unicentric, unilateral, invasive disease without neoadjuvant therapy were collected in a database. The recommendations of the Austrian Sentinel Node Study Group were to complete a training period (phase I) with 50 cases of SNB followed by axillary lymph node dissection (ALND) to prove a detection rate of > or = 90% and a false-negative rate of < or = 5%. In the executing period (phase II), SNB was followed by ALND only if the sentinel node (SN) contained metastases. We compared the results on disease-free survival, local recurrence rates, distant recurrence rates and overall survival of both groups. Cases from phases I and II generated groups I (n=671) and 2 (n=2271 cases), respectively. RESULTS: Overall mean follow-up time: 34.41 months. CONCLUSION: SNB followed by ALND only in cases with metastases in the SN is a safe procedure and at least equal to ALND in all cases.

HMGA2 is associated with invasiveness but not a suitable marker for the detection of circulating tumor cells in breast cancer.

Previously, the human high mobility group protein member HMGA2 mRNA was reported to be expressed in peripheral blood of patients with breast cancer, but not in healthy individuals. Expression of HMGA2 in blood was suggested to be an independent indicator of poor prognosis in metastatic breast cancer. These very promising findings propose HMGA2 as a potential marker for the detection of circulating tumor cells in peripheral blood. Therefore, we analyzed peripheral blood specimens from healthy controls and patients with breast tumors for HMGA2 expression using TaqMan real-time RT-PCR to test if HMGA2 is a suitable marker for the early detection of breast cancer and monitoring therapy response in peripheral blood. Furthermore, we examined the possible involvement of HMGA2 expression in invasion investigated by an in vitro invasion assay using established breast cell lines. HMGA2 expression was detected in peripheral blood of breast cancer patients as well as of healthy individuals. No significant association of HMGA2 expression with any clinical or histopathological data was apparent. However, there was a significant correlation of HMGA2 expression in invasive and non invasive breast cell lines (p=0.0056). Although, HMGA2 obviously contributes to invasion it is not a specific marker for the detection of circulating tumor cells in peripheral blood.

Pattern of hormone receptor status of secondary contralateral breast cancers in patients receiving adjuvant tamoxifen.

In breast cancer patients receiving adjuvant tamoxifen after unilateral treatment, contralateral breast cancer (CBC) is extremely rare. As a result, only limited data are available on the hormone receptor status of CBCs evolving in tamoxifen-treated patients. The aim of our investigation was to evaluate the pattern of hormone receptor status of CBCs in patients treated with adjuvant tamoxifen at our institution. Material was collected from 35 patients. We have found that 27 of the 35 patients included into our investigation developed an estrogen receptor (ER)-positive CBC despite adjuvant tamoxifen. Seven ER-positive CBCs occurred after tamoxifen had been discontinued, and 20 patients developed an ER-positive CBC while receiving tamoxifen. Notably, 80% of these CBCs displayed moderate-to-strong levels of ER. In our opinion, the selection of ER-negative CBCs, which has previously been implicated to be the pivotal mechanism of tumor escape of CBCs evolving in tamoxifen-treated patients, is only one mechanism of tumor escape in patients receiving antiestrogen treatment. The emergence of ER-positive CBCs in the majority of tamoxifen-treated patients suggests that alternative escape mechanisms may be equally relevant. These include the emergence of ER-positive CBCs that display tamoxifen-dependent growth properties, the selection of CBCs that are tamoxifen resistant because of ER mutations with altered ER function, and, finally, the selection of ER-positive CBCs that overexpress c-erbB2.

Young age as an independent adverse prognostic factor in premenopausal patients with breast cancer.

Breast cancer in younger patients appears to be more aggressive than disease occurring in older patients. Even though large population-based studies suggest poorer survival of patients younger than 35 years, data demonstrating the relationship of age and prognosis within premenopausal cohorts are much more scarce and conflicting. In this retrospective analysis of 885 premenopausal patients, the relationship between age, typical prognostic factors, treatment, and patient outcome was investigated. Eight hundred four patients (90.8%) > 35 years and 81 patients (9.2%) = 35 years who had been treated for stage I/II breast cancer were evaluated. Median follow-up time was 71 months. The prevalence of adverse prognostic features such as tumor size, tumor type, tumor grading, pathologic lymph node status, and hormone receptor status were evenly distributed between the two age groups. Age = 35 years proved to be a powerful independent prognostic factor in multivariate analyses of recurrence-free (P < 0.0001; relative risk [RR] = 2.5) and overall survival (P < 0.0039, RR = 2.2). Thus, in the face of evenly distributed risk factors in this strictly premenopausal, homogeneous population, young age was seen as the second most powerful risk factor after lymph node status. According to these findings, patients diagnosed with breast cancer at = 35 years of age have a worse prognosis compared to premenopausal women above this age. Future studies should focus on unveiling the young age surrogate in order to improve treatment and prognosis.

Prognostic markers in breast cancer: the reliability of HER2/neu status in core needle biopsy of 325 patients with primary breast cancer.

INTRODUCTION: The assessment of HER2/neu overexpression in tissue provides information about one of the most relevant prognostic and predictive markers in breast cancer: overexpression of HER2/neu is associated with worse prognosis in primary breast cancer. Since core needle biopsy is increasingly used for the diagnosis of breast cancer, the purpose of this study was to assess the reliability of HER2/neu evaluation using this technique in patients with primary breast cancer. PATIENTS AND METHODS: We investigated the accuracy of immunohistochemical assessment of HER2/neu in core needle biopsies compared with surgically obtained specimens in 325 patients with primary breast cancer. In patients strongly positive for HER2/neu, additional fluorescence in situ hybridization (FISH) analysis of needle biopsies was performed. RESULTS: Using immunohistochemistry alone, accuracy of HER2/neu assessment in core biopsies in relation to surgically removed specimens was 92% and increased to 96% with additional FISH analysis (weighted Kappa coefficient: 0.86). DISCUSSION: As proven with this large series of patients, the assessment of HER2/neu status by core needle biopsy in breast cancer is accurate. Notwithstanding, in order to minimize the number of false-positive results, strongly positive core needle biopsies identified using immunohistochemistry should be confirmed by FISH analysis.

The labelling of Nanocoll with [111In] for dual-isotope scanning.

UNLABELLED: Visualization and biopsy of sentinel lymph nodes play an important role in planning and controlling the therapy of breast cancer. Hitherto two methods-scintigraphy or gamma probe detection after injection of [99mTc]-nanocolloids and visual detection after injection of patent blue dye-are used routinely. There are no conclusive publications elucidating such important parameters as injection site, injection method and colloidal parameters. The present work aims to label Nanocoll with [111In] to provide an alternative method, a simultanous one-compound dual-isotope application. METHODS: [111In]-Indiumchloride was buffered with acetate and transferred to the nanocolloid. The colloid labelling reaction was complete after 30 min and filtrated through 100 nm Nuclepore filters. RESULTS: Incorporation yield of [111In]-Indium into the nanocolloid was nearly quantitative, the step associated with the major loss of activity was the particle sizing with a mean yield of 55%. CONCLUSION: The presented method allows for the routine supply of [111In]-nanocolloids. Size-filtered [111In]-Nanocoll shows the same particle size range as [99mTc]-Nanocoll.

[Consensus statement haemorrhoidal disease]. / Konsensusbericht Hämorrhoidalleiden.

Haemorrhoidal disease belongs to the most common benign disorders in the lower gastrointestinal tract. Treatment options comprise conservative as well as surgical therapy still being applied arbitrarily in accordance with the surgeon's expertise. The aim of this consensus statement was therefore to assess a stage-dependent approach for treatment of haemorrhoidal disease to derive evidence-based recommendations for clinical routine. The most common methods are discussed with respect of haemorrhoidal disease in extraordinary conditions like pregnancy or inflammatory bowel disease and recurrent haemorrhoids. Tailored haemorrhoidectomy is preferable for individualized treatment with regard to the shortcomings of the traditional Goligher classification in solitary or circular haemorrhoidal prolapses.

Prevalence of anal HPV infection in solid-organ transplant patients prior to immunosuppression.

Patients that undergo organ transplantation have a high risk of developing various malignancies, depending on the duration and magnitude of immunosuppressive therapy. Among others, a 10-fold increased relative risk has been reported for the development of anal cancer. There is a strong association between persistent infection with high-risk mucosal types of human papillomavirus (HPV) and anogenital neoplasia. In this study we analysed the prevalence of anal HPV infection in organ transplant patients before starting immunosuppressive therapy. In a university transplant unit, patients ( n=60, 40 male, 20 female) that were undergoing solid-organ transplantation (kidney, liver) for the first time were routinely screened for anal HPV infection. Anal swabs were obtained within 24 h after transplantation and analysed for the presence of mucosal-type HPV DNA by liquid DNA/RNA hybridization [hybrid capture (HC) 2 test]. Overall, some type of HPV DNA was detected in 14/60 (23.3%) patients; 9/60 (15%) were positive for high-risk HPV and 8/60 (13.4%) were positive for low-risk HPV, and 3/60 (5%) were positive for both types. Prevalence of HPV infection tended to be higher in patients that were receiving liver transplants than in those receiving kidney transplants (29.4% vs. 20.9%), but the difference did not reach statistical significance. In our series of organ transplant patients the prevalence of previous HPV infection (23.3%) before immunosuppressive therapy was started was higher than that found in previous epidemiological studies or in a control group. In particular, there was a high rate (15%) of infection with oncogenic HPV types. These findings have important implications on screening and surveillance policies in this patient group at risk of developing neoplasias, including anal cancer.

Monitoring of circulating angiogenic factors in dendritic cell-based cancer immunotherapy.

BACKGROUND: A promising treatment approach for patients with malignant disease that recently has found its way into clinical trials is based on vaccination with autologous dendritic cells loaded with tumor antigens. However, adequate assays for monitoring clinical and immunologic responses still are under debate. In recent years, the determination of angiogenic markers has shown considerable potential in the diagnosis and prognosis of patients with malignant disease, because tumor growth and spread are promoted by angiogenesis, the formation of new blood vessels. METHODS: The authors established a method for measuring the plasma levels of three modulators of angiogenesis: vascular endothelial growth factor, platelet-derived endothelial cell growth factor, and thrombospondin-1. The angiogenic blood profile of a healthy control group was characterized and compared with a group of patients with malignant disease. Ultimately, levels of circulating angiogenic factors were monitored in the course of dendritic cell-based cancer immunotherapy. RESULTS: Baseline levels of angiogenic mediators varied substantially among healthy individuals but showed consistent values for each individual. Blood levels of circulating angiogenic factors were elevated significantly in patients with advanced disease and were highly sensitive to dendritic cell-based immunotherapy. CONCLUSIONS: To our knowledge, the current report was the first to analyze circulating levels of angiogenic factors during dendritic cell-based immunotherapy. The authors observed a noteworthy change in the angiogenic blood profile with treatment, and this change was correlated with the induction of an immunologic response.

Do we need HER-2/neu testing for all patients with primary breast carcinoma?

BACKGROUND: HER-2/neu is a valuable prognostic marker in primary breast carcinoma. Controversy surrounds the correlation between HER-2/neu expression and other prognostic markers, as has been discussed in preclinical and clinical studies. The objective of the current study was to investigate the probability, calculated using parameters that are assessed routinely in clinical practice, that patients with breast carcinoma had positive HER-2/neu status. METHODS: The authors evaluated HER-2/neu status in 923 consecutive patients with breast carcinoma by immunohistochemical methods. Correlations involving HER-2/neu status, estrogen receptor (ER) and progesterone receptor (PR) status, tumor grade, patient age, lymph node involvement, and tumor size were evaluated using the Mantel-Haenszel chi-square test and the Spearman correlation. The authors created a simple scoring system (i.e., the diagnostic instrument for validation of HER-2/neu score) to define subgroups of patients with breast carcinoma and to determine the likelihood of HER-2/neu positivity. RESULTS: HER-2/neu overexpression was correlated significantly with negative ER (P = 0.0001) and PR status (P = 0.0001), Grade 3 (G3) lesions (P = 0.0001), and young age (P = 0.006). The likelihood of HER-2/neu positivity in a patient with positive ER and PR status and G1/G2 disease was approximately 6.1%. CONCLUSIONS: The authors demonstrated in a large patient series that HER-2/neu overexpression was associated with negative hormone receptor status, G3, and young age. In a subgroup of patients presenting with hormone-responsive and G1/G2 tumors, the likelihood of HER-2/neu overexpression was very small. Therefore, the assessment of HER-2/neu status in this subgroup of patients with breast carcinoma may be considered unnecessary, unless the role of HER-2/neu status in adjuvant treatment has been proven.

Influence of neoadjuvant therapy with epirubicin and docetaxel on the expression of HER2/neu in patients with breast cancer.

BACKGROUND: In primary breast cancer, the expression levels of biological markers relevant to the progression of the disease may be altered by administration of anticancer drugs. Since neoadjuvant chemotherapy with epirubicin and docetaxel is increasingly used in advanced breast cancer, our purpose was to assess the influence of this neoadjuvant chemotherapy on the expression of the growth factor receptor HER2/neu. PATIENTS AND METHODS: We investigated changes of HER2/neu status by immunohistochemistry (IHC) and applied additional fluorescence in situ hybridization (FISH) in patients with potential modulation of HER2/neu status after administration of neoadjuvant chemotherapy with docetaxel and epirubicin in 97 breast cancer patients. The influence of neoadjuvant chemotherapy on HER2/neu expression was calculated by correlation of HER2/neu status before and after chemotherapy. RESULTS: The accuracy of HER2/neu assessment before and after neoadjuvant chemotherapy by IHC combined with FISH analysis in selected cases was 100%. The evaluation of HER2/neu status in these patients by IHC alone yielded accuracy of 93%. Neoadjuvant chemotherapy with epirubicin and docetaxel caused no significant modulation of HER2/neu status (p = 0.66). DISCUSSION: The administration of epirubicin and docetaxel in the neoadjuvant setting is not associated with significant changes of HER2/neu status in primary breast cancer. As a consequence, drug resistance or sensitivity is not induced by modulation of HER2/neu expression. Moreover, the time of assessment of the HER2/neu status is not a critical factor under neoadjuvant therapy with epirubicin and docetaxel.