Enhanced Recovery after Surgery Protocol for Pediatric Urological Augmentation and Diversion Surgery Using Small Bowel.

PURPOSE: Enhanced recovery after surgery protocols aim to improve recovery following urological augmentation and diversion surgery. Based on the positive experiences in adult patients, we evaluated safety and outcomes after implementation of an enhanced recovery after surgery protocol in children undergoing urological augmentation and diversion using small bowel. MATERIALS AND METHODS: Complications, time to stool, time to flatus and total hospital stay of 15 consecutive patients (group 2) were recorded and compared to the data of 15 consecutive patients before the changes in protocol were effective (group 1). The groups were comparable in age (mean 10.93 vs 9.267 years, p = 0.33), gender (p = 0.71) and operative times (387.9 vs 336.5 minutes, p = 0.19). RESULTS: Compared to the previous protocol involving a mean ± SD of 7.9 ± 1.38 enhanced recovery after surgery items per patient, 15.9 ± 0.26 items per patient were implemented in the new protocol. In group 2 mild bowel related complications were less frequent (1 vs 5, p = 0.168). Time to stool was significantly shorter in group 2 (3.33 vs 5.53 days, p = 0.002), as was time to flatus (2.8 vs 4.73 days, p = 0.002). Total hospital stay in group 2 was 11.93 days, compared to 19.87 days in group 1 (p <0.001), mainly due to more rapid convalescence, although influenced by associated changes in the postoperative protocol as well. CONCLUSIONS: In pediatric augmentation and diversion surgery using small bowel the implementation of an enhanced recovery after surgery protocol is safe and effective, reinforcing faster bowel recovery. We did not observe complications or problems after introducing the new protocol.

Evaluation of BRCA1/2 mutational status among German and Austrian women with triple-negative breast cancer.

PURPOSE: Testing for BRCA1 and BRCA2 mutations in breast cancer patients is used to identify the risk of second primary cancers and the risk of cancer in the patients' family. Women with triple-negative breast cancer (TNBC) are thought to be more likely to be BRCA1/2 mutation carriers, but most national guidelines for genetic testing, including those used in Germany and Austria, do not consider receptor triple negativity. METHODS: We determined the prevalence of BRCA1 and BRCA2 mutations within a cohort of 100 unselected TNBC cases, including patients from Germany and Austria to identify those BRCA-positive patients with a masked family history and who would have been missed due to respective current national guidelines. Double-stranded Sanger sequencing of all exons of BRCA1 and BRCA2, respectively, was performed. RESULTS: We identified a total of 13 deleterious mutations in BRCA1 and a total of four deleterious mutations in BRCA2. The total rate of deleterious BRCA1/2 mutation carriers was 21 % in our cohort. Six novel mutations, including two deleterious mutations, have been identified, which have not been described in public mutation databases so far. According to current German and Austrian national guidelines for genetic testing, 38.1 and 52.4 %, respectively, of BRCA1/2 mutation carriers would have been overlooked. CONCLUSIONS: We conclude that the prevalence of BRCA1 and BRCA2 mutations is high in TNBC patients and that BRCA1/2 mutations are not restricted to young women or patients with a positive family history. Receptor triple negativity should therefore be considered in BRCA1/2 genetic testing guidelines.

Adjuvant sequencing of tamoxifen and anastrozole is superior to tamoxifen alone in postmenopausal women with low proliferating breast cancer.

PURPOSE: To assess the predictive value of Ki67 expression in postmenopausal hormone receptor-positive early-breast cancer patients, who were either treated with adjuvant tamoxifen (TAM) alone or with TAM followed by anastrozole (ANA). EXPERIMENTAL DESIGN: Expression of Ki67 was determined centrally by immunohistochemistry on whole tissue sections of postmenopausal endocrine-responsive breast cancers from patients who had been enrolled in the prospectively randomized Austrian Breast and Colorectal Cancer Study Group Trial 8, and had received TAM for 5 years, or TAM for 2 years followed by ANA for 3 years. Ki67 expression was evaluated both as a continuous variable and dichotomized to low (≤10%) and high (>10%). Recurrence-free survival (RFS) and overall survival (OS) were analyzed using Cox models adjusted for clinical and pathologic parameters. RESULTS: Patients with a high Ki67 expression (394/1,587; 23%) had a significantly shorter RFS (adjusted HR for recurrence = 1.90, 95% CI: 1.37-2.64, P = 0.0001) and OS (adjusted HR for death = 1.78, 95% CI: 1.18-2.70, P = 0.006). In women with breast tumors expressing medium or high ER levels (n = 1,438), the interaction between Ki67 and adjuvant endocrine treatment was significant for RFS (P = 0.03). TAM followed by ANA was superior to TAM alone in patients with low Ki67 (adjusted HR = 0.53, 95% CI: 0.34-0.83, P = 0.005) but not in high Ki67 disease (adjusted HR = 1.18, 95% CI: 0.66-1.89, P = 0.68). CONCLUSIONS: Adjuvant sequencing of TAM and ANA is superior to TAM alone, particularly in postmenopausal women with medium or high ER expressing, low proliferating breast cancer.

Sentinel node biopsy after primary chemotherapy in breast cancer: a note of caution from results of ABCSG-14.

Over the past years, experience has been increasing with lymphatic mapping and sentinel node biopsy (SNB) after preoperative chemotherapy for breast cancer, with a wide range of results reported in the literature and final conclusions on the diagnostic value and clinical consequences of this sequential approach still missing. Between 1999 and 2002, the Austrian Breast and Colorectal Cancer Study Group (ABCSG) conducted a prospective randomized multicenter trial comparing three versus six preoperative cycles of epirubicin/docetaxel + granulocyte colony-stimulating factor for operable breast cancer. Of the 292 patients recruited to the trial overall, 111 were enrolled in a prospective subprotocol for performing LM and SNB in addition to obligatory axillary lymph node dissection (ALND) after PC. SNB after PC identified at least one sentinel node in 100 of 111 patients (identification rate 90%). In six cases, a false-negative SN was identified, resulting in a false-negative rate of 13% (6 of 47). We only found little correlation between patients and tumor characteristics and the identification rate or false-negative rate. Lymphatic mapping and SNB after primary chemotherapy failed to predict histologic infiltration of the sentinel node with sufficient sensitivity. The routine use of SNB after primary chemotherapy should therefore be discouraged.

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.

Complications after oesophagectomy with possible contribution of neoadjuvant therapy including an EGFR-antibody to a fatal outcome.

BACKGROUND: Different molecular therapies like the EGFR-inhibiting antibody cetuximab have come into clinical practice. Cetuximab is EMEA-approved for metastatic colorectal cancer and advanced squamous-cell head and neck cancer. Administration is said to be safe and well tolerated with common, usually mild dermatologic side effects. CASE PRESENTATION: We present the case of a patient with fatal complications after oesophagectomy and neoadjuvant chemotherapy including cetuximab for squamous-cell esophageal cancer. A transthoracic en-bloc oesophagectomy was performed. Few days later the patient died due to gas exchange dysfunction and circulation instability after a previously unseen combination of drain-erosion of the stomach with subsequent pleurisy and air leak of the left main bronchus. CONCLUSION: So far we have never observed this fatal combination of drain erosion of the stomach with fibrinous pleurisy and unmanageable progressive tracheal defect before. The role of cetuximab in the multifactorial aetiology of damages of stomach and trachea after oesophagectomy remains unclear since we are not able to link the complication directly to cetuximab or definitely exclude it as a sole surgical complication. Clinicians should be aware of the possibility of fatal side effects and careful recording of all complications is necessary in ongoing and planned studies to obtain more evidence about safety and tolerance of targeted therapies.

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.

Intra-operative sonography: a valuable aid during breast-conserving surgery for occult breast cancer.

BACKGROUND: Breast cancer is increasingly detected during an early non-palpable stage. Together with pre-operative marking of the mass, intra-operative imaging provides invaluable clues. This study was designed to evaluate the usefulness of intra-operative sonography in the hands of the surgeon. METHODS: Between July 2001 and October 2006, 567 patients underwent treatment for operable breast cancer at the landeskrankenhaus (LHK) Feldkirch. Three hundred and sixty lesions were not palpable. Two hundred and ninety-nine patients with poorly definable or non-definable lesions well seen by ultrasound imaging underwent intra-operative sonography (group 1), while 61 patients with non-palpable lesions only seen on mammography (group 2) were subjected to pre-operative needle localization. The study was non-randomized with prospective data acquisition RESULTS: All lesions were identified by both sonography and pre-operative needle localization. In the ultrasound group (group 1) 81% of the lesions were successfully removed by primary intention without metachronous secondary surgery versus 62% in group 2 (p < 0.00228). Eighty-eight percent of the lesions in group 1 were eligible for breast-conserving surgery versus 75% in group 2. The mean clear margin in group 1 was substantially smaller (4.8 mm) than in group 2 (7.2 mm) (p < 0.0001). CONCLUSION: Intra-operative sonography proved to be a reliable and helpful tool in the hands of the surgeon, not only for tumor localization, but also for orientation during tumor excision. It simplifies organizational work and spares the patient the discomfort of pre-operative needle localization.

Pathologic complete response with six compared with three cycles of neoadjuvant epirubicin plus docetaxel and granulocyte colony-stimulating factor in operable breast cancer: results of ABCSG-14.

PURPOSE: Preoperative (neoadjuvant) chemotherapy for operable breast cancer downstages tumors initially not suitable for breast-conserving surgery. A pathologic complete response (pCR) to neoadjuvant chemotherapy may be a surrogate for longer overall survival, but this beneficial effect remains to be established. This phase III trial evaluated whether doubling the number of cycles of neoadjuvant treatment increased the pCR rate. PATIENTS AND METHODS: Patients with biopsy-proven breast cancer (T1-4a-c, N+/-, M0; stage I to III) were eligible and randomly assigned to either three or six cycles of epirubicin 75 mg/m2 and docetaxel 75 mg/m2 on day 1 and granulocyte colony-stimulating factor on days 3 through 10 (ED+G), every 21 days. The primary end point was the pCR rate of the breast tumor. Secondary end points were pathologic nodal status after surgery and the rate of breast-conserving surgery. RESULTS: A total of 292 patients were accrued, and 288 patients were assessable for efficacy and safety. Groups were well balanced for known prognostic factors. Six cycles of ED+G, compared with three cycles, resulted in a significantly higher pCR rate (18.6% v 7.7%, respectively; P = .0045), a higher percentage of patients with negative axillary status (56.6% v 42.8%, respectively; P = .02), and a trend towards more breast-conserving surgery (75.9% v 66.9%, respectively; P = .10). Rates of adverse events were similar, and no patients died on treatment. CONCLUSION: Doubling the number of neoadjuvant ED+G cycles from three to six results in higher rates of pCR and negative axillary nodal status with no excess of adverse effects. Thus, six cycles of ED+G should be the standard neoadjuvant treatment for operable breast cancer if this combination is chosen.

Invasive ductal carcinoma and invasive lobular carcinoma of breast differ in response following neoadjuvant therapy with epidoxorubicin and docetaxel + G-CSF.

PURPOSE: Preoperative chemotherapy in patients with primary breast cancer treated with anthracyclines and taxanes results in high response rates, allowing breast conserving surgery (BCS) in patients primarily not suitable for this procedure. Pathological responses are important prognostic parameters for progression free and overall survival. We questioned the impact of histologic type invasive ductal carcinoma (IDC) versus invasive lobular carcinoma (ILC) on response to primary chemotherapy. PATIENTS AND METHODS: 161 patients with breast cancer received preoperative chemotherapy consisted of epidoxorubicin 75 mg/m(2) and docetaxel 75 mg/m(2) administered in combination with granulocyte-colony stimulating factor (G-CSF) on days 3-10 (ED + G). Pathological complete response (pCR), biological markers and type of surgery as well as progression free and overall survival were compared between IDC and ILC. RESULTS: Out of 161 patients, 124 patients presented with IDC and 37 with ILC. Patients with ILC were less likely to have a pCR (3% vs. 20%, P < 0.009) and breast conserving surgeries (51% vs. 79%, P < 0.001). Patients with ILC tended to have oestrogen receptor positive tumors (86% vs. 52%, P < 0.0001), HER 2 negative tumors (69% vs. 84%), and lower nuclear grade (nuclear grade 3, 16% vs. 46%, P < 0.001). Patients with ILC tended to have longer time to progression (TTP) (42 months vs. 26 months) and overall survival (69 months vs. 65 months). CONCLUSIONS: Our results indicate that patients with ILC achieved a lower pCR rate and ineligibility for BCS to preoperative chemotherapy, but this did not result in a survival disadvantage. Because of these results new strategies to achieve a pCR are warranted.

Multicentric breast cancer: a new indication for sentinel node biopsy--a multi-institutional validation study.

PURPOSE: Multicentric breast cancer has been considered to be a contraindication for sentinel node (SN) biopsy (SNB). In this prospective multi-institutional trial, SNB-feasibility and accuracy was evaluated in 142 patients with multicentric cancer from the Austrian Sentinel Node Study Group (ASNSG) and compared with data from 3,216 patients with unicentric cancer. PATIENTS AND METHODS: Between 1996 and 2004, 3,730 patients underwent SNB at 15 ASNSG-affiliated hospitals. Patient data were entered in a multicenter database. One hundred forty-two patients presented with multicentric invasive breast cancer and underwent SNB. RESULTS: Intraoperatively, a mean number of 1.67 SNs were excised (identification-rate, 91.5%). The incidence of SN metastases was 60.8% (79 of 130). This was confirmed by axillary lymph node dissection (ALND) in 125 patients. Of patients with positive SNs, 60.8% (48 of 79) showed involvement of nonsentinel nodes (NSNs), as did three patients with negative SNs (false-negative rate, 4.0). Sensitivity, negative predictive value, and overall accuracy were 96.0%, 93.3%, and 97.3%, respectively. Ninety-one percent of the patients underwent mastectomy, and 9% were treated with breast conserving surgery. None of the patients have shown axillary recurrence so far (mean follow-up, 28.8 months). Compared with 3,216 patients with unicentric cancer, there was a significantly higher rate of SN metastases as well as in NSNs, whereas there was no difference in detection and false-negative rates. CONCLUSION: Multicentric breast cancer is a new indication for SNB without routine ALND in controlled trials. Given adequate quality control and an interdisciplinary teamwork of surgical, nuclear medicine, and pathology units, SNB is both feasible and accurate in this disease entity.

[Sentinel node biopsy in breast cancer: techniques and indications]. / Sentinel Node Biopsie beim Mammakarzinom: Technik und Indikation.

Sentinel node biopsy (SNB) has proved to be a useful and accurate procedure for lymph node staging in breast cancer and melanoma and should be standard of care in the treatment of these tumors. In other malignancies (colon, rectum, stomach, esophagus, head and neck and thyroid, cervix uteri) it is still under investigation. SNB in breast cancer was accepted as a sole and reliable diagnostic method in breast cancer from the panel of distinguished experts at the 8th international conference of primary therapy of early breast cancer 2003 in St. Gallen. Combination of the current techniques with radiocolloids and blue dye, applicated superficially (intradermal, subdermal, peri- and subareolar) and deeply (peritumoral, intratumoral, subtumoral) enables high identification rates and negative predictive values. It should be performed by teams consisting of surgeons, pathologists and nuclear medicine specialists with appropriate training and experience. Accepted indications are uni- and multifocal tumors smaller than 3 cm without suspicious findings in the axilla, furthermore SNB is indicated in patients with large ductal carcinoma in situ (>2cm) and/or with assumed microinvasion. Albeit SNB could be shown to be safe after preoperative chemotherapy and in multicentric breast cancer, due to lack of sufficient data it is still under discussion in these cases. Expedience of this procedure in other lymph node basins, along the mammaria interna vessels or in the infra- and supraclavicular region is considered to be at an investigative stage as well. SNB allows the pathologist to focus on a small number of nodes most likely to contain metastases. Application of serial sectioning and immunhistochemistry results in a more accurate staging than routine examination. Detection of additional micrometastases that are found in 10-15% leads to an upgrading from N0 to N1. Broad application and refurbishment led to scientific discussion of prognostic importance of micrometastases and its relevance according axillary dissection and adjuvant systemic treatment. Although many unicentric and multicentric observational studies validated by complete axillary dissection could demonstrate that SNB is accurate and suitable for all operable clinically node-negative breast cancers, longterm results and especially the incidence of axillary recurrence and its sequelae are outstanding. Findings of ongoing large prospective randomized trials like NSABP 32, Z0010 and Z0011 of the American College of Surgeons (ACOSOG), the AMAROS-Trial of the European Organisation of Research and Treatment of Cancer (EORTC) and the ALMANAC-Trial of the British Association of Surgical Oncology (BASO) will give a conclusive answer. Significant improvement in morbidity and quality of life measurements could be revealed several times in unicentric and even in muticentric studies like ALMANAC. Sentinel node biopsy is a team approach, requirements are good cooperation and well-defined stuctures of quality indicators and documentation. Participation in national clinical studies is recommended.

[Mesenteric inflammatory veno-occlusive disease (MIVOD)--a rare cause of intestinal ischemia]. / Mesenteric inflammatory veno-occlusive disease (MIVOD)--seltene Ursache für intestinale Ischämie.

Mesenteric inflammatory veno-occlusive disease (MIVOD) is a relatively recently known and not very often diagnosed form of ischemic bowel disease of low incidence und unknown etiology. We present the case of a patient who after presentation of inconclusive signs of epigastric pain and rectal bleeding suddenly developed right abdominal pain with local peritonism. Suspecting intestinal ischemia or perforated appendicitis we first performed laparoscopy, which showed an inflammable tumor of cecum, ascending colon and appendix with massive adhesions to the abdominal wall. We performed an open right hemicolectomy with primary anastomosis. The patient developed a deep vein thrombosis of the vena tibialis post. and vena saphena parva. After 12 months our patient is free of complaints and recurrence. Investigations carried out showed no evidence of hypercoagulopathy. The presentation of MIVOD can range from chronic inflammatory bowel disease with recurrent abdominal pain in combination with nausea, emesis and bloody diarrhea to acute abdomen. Therefore diagnostic misinterpretation and mistherapy as well as underdiagnosis is common. Histologic investigation shows a variable inflammatory infiltration of multiple veins of the intestinal wall and the mesentery as well as thrombotic vessel occlusion in different stages without involvement of the arteries. All forms of hypercoagulopathy, parasitic disease, sepsis and malignancy have to be excluded. Therapeutic success can only be achieved with surgical resection of the affected bowel, whereon in general no recurrence will occur.

Morbidity of breast cancer patients following complete axillary dissection or sentinel node biopsy only: a comparative evaluation.

INTRODUCTION: The usefulness of routine axillary dissection (AD) at levels I-II in breast cancer patients has been questioned for years because of the high postoperative morbidity in the shoulder and arm region, and the increasing number of patients with negative nodes. Sentinel node biopsy (SNB) was hoped both to reduce morbidity and to improve the reliability of staging. This study was designed to provide more evidence in this matter by comparing the follow-up data of patients with AD and those with SNB only. METHOD: One hundred forty patients who had undergone AD between 1993 and 1996 were questioned for their subjective and objective symptoms using a questionnaire and subsequently subjected to a clinical examination. Their data were compared with those of 57 patients who had undergone SNB only between 1998 and 2000. RESULTS: Local recurrences have not been seen to date. The difference between the two groups in terms of a loss of quality of life was negligible. The differences in overall complaints, number of symptoms, pain, limited range of motion of the operated upper extremity, numbness, paresthesias, and arm swelling as well as perceived disability in activities of daily living were significantly in favor of SNB. The length of hospital stay was significantly shorter for SNB patients. CONCLUSION: SNB appears to be an accurate procedure for axillary nodal staging in breast cancer patients and is associated with reduced postoperative morbidity and length of hospital stay. But it is still investigational and should not be implemented as therapeutical standard before results of randomized trials are published.

Total parathyroidectomy with autotransplantation in renal hyperparathyroidism: low recurrence after intra-operative tissue selection.

BACKGROUND: Total parathyroidectomy with simultaneous autotransplantation (AT) is a well-established surgical modality in the treatment of severe drug-resistant renal hyperparathyroidism. In literature, the high rate of graft-dependent recurrence seems a serious disadvantage. This complication can possibly be avoided by parathyroid tissue selection prior to AT. METHODS: Total parathyroidectomy with simultaneous AT was performed in 37 patients on intermittent haemodialysis treatment. Parathyroid tissue with a low proliferative potential ('A-regions') was selected for AT intra-operatively with a stereomagnifier. The mean post-operative follow-up was 37+/-24 months. RESULTS: Plasma levels of intact parathyroid hormone decreased from 1211+/-541 to 69+/-32 pg/ml, calcium from 2.49+/-0.27 to 2.17+/-0.30 mmol/l, phosphorus from 2.28+/-0.63 to 2.11+/-0.69 mmol/l, and total alkaline phosphatases from 272+/-210 to 117+/-70 U/l. Graft-dependent recurrent hyperparathyroidism occurred in one patient after 32 months and was cured by the selective removal of five enlarged autografts. CONCLUSIONS: Simply discriminating between diffuse and nodular hyperplastic parathyroid tissue appears to be inadequate. Intra-operative tissue selection with a stereomagnifier may facilitate the identification and AT of tissue with optimal functional characteristics and a low proliferative potential, thus minimizing the rate of recurrent hyperparathyroidism.