5-year results of accelerated partial breast irradiation using sole interstitial multicatheter brachytherapy versus whole-breast irradiation with boost after breast-conserving surgery for low-risk invasive and in-situ carcinoma of the female breast: a randomised, phase 3, non-inferiority trial.

BACKGROUND In a phase 3, randomised, non-inferiority trial, accelerated partial breast irradiation (APBI) for patients with stage 0, I, and IIA breast cancer who underwent breast-conserving treatment was compared with whole-breast irradiation. Here, we present 5-year follow-up results. METHODS We did a phase 3, randomised, non-inferiority trial at 16 hospitals and medical centres in seven European countries. 1184 patients with low-risk invasive and ductal carcinoma in situ treated with breast-conserving surgery were centrally randomised to either whole-breast irradiation or APBI using multicatheter brachytherapy. The primary endpoint was local recurrence. Analysis was done according to treatment received. This trial is registered with ClinicalTrials.gov, number NCT00402519. FINDINGS Between April 20, 2004, and July 30, 2009, 551 patients had whole-breast irradiation with tumour-bed boost and 633 patients received APBI using interstitial multicatheter brachytherapy. At 5-year follow-up, nine patients treated with APBI and five patients receiving whole-breast irradiation had a local recurrence; the cumulative incidence of local recurrence was 1·44% (95% CI 0·51-2·38) with APBI and 0·92% (0·12-1·73) with whole-breast irradiation (difference 0·52%, 95% CI -0·72 to 1·75; p=0·42). No grade 4 late side-effects were reported. The 5-year risk of grade 2-3 late side-effects to the skin was 3·2% with APBI versus 5·7% with whole-breast irradiation (p=0·08), and 5-year risk of grade 2-3 subcutaneous tissue late side-effects was 7·6% versus 6·3% (p=0·53). The risk of severe (grade 3) fibrosis at 5 years was 0·2% with whole-breast irradiation and 0% with APBI (p=0·46). INTERPRETATION The difference between treatments was below the relevance margin of 3 percentage points. Therefore, adjuvant APBI using multicatheter brachytherapy after breast-conserving surgery in patients with early breast cancer is not inferior to adjuvant whole-breast irradiation with respect to 5-year local control, disease-free survival, and overall survival. FUNDING German Cancer Aid.

Recommendations from GEC ESTRO Breast Cancer Working Group (I): Target definition and target delineation for accelerated or boost Partial Breast Irradiation using multicatheter interstitial brachytherapy after breast conserving closed cavity surgery

OBJECTIVE The aim was to develop a delineation guideline for target definition for APBI or boost by consensus of the Breast Working Group of GEC-ESTRO. PROPOSED RECOMMENDATIONS Appropriate delineation of CTV (PTV) with low inter- and intra-observer variability in clinical practice is complex and needs various steps as: (1) Detailed knowledge of primary surgical procedure, of all details of pathology, as well as of preoperative imaging. (2) Definition of tumour localization before breast conserving surgery inside the breast and translation of this information in the postoperative CT imaging data set. (3) Calculation of the size of total safety margins. The size should be at least 2 cm. (4) Definition of the target. (5) Delineation of the target according to defined rules. CONCLUSION Providing guidelines based on the consensus of a group of experts should make it possible to achieve a reproducible and consistent definition of CTV (PTV) for Accelerated Partial Breast Irradiation (APBI) or boost irradiation after breast conserving closed cavity surgery, and helps to define it after selected cases of oncoplastic surgery.

Neoadjuvant interstitial high-dose-rate (HDR) brachytherapy combined with systemic chemotherapy in patients with breast cancer

BACKGROUND AND PURPOSE: This is the first study investigating neoadjuvant interstitial high-dose-rate (HDR) brachytherapy combined with chemotherapy in patients with breast cancer. The goal was to evaluate the type of surgical treatment, histopathologic response, side effects, local control, and survival. PATIENTS AND METHODS: 53 patients, who could not be treated with breast-conserving surgery due to initial tumor size (36/53) or due to an unfavorable breast-tumor ratio (17/53), were analyzed retrospectively. All but one were in an intermediate/high-risk group (St. Gallen criteria). The patients received a neoadjuvant protocol consisting of systemic chemotherapy combined with fractionated HDR brachytherapy (2 x 5 Gy/day, total dose 30 Gy). In cases, where breast-conserving surgery was performed, patients received additional external-beam radiotherapy (EBRT, 1.8 Gy/day, total dose 50.4 Gy). In patients, who underwent mastectomy but showed an initial tumor size of T3/T4 and/or more than three infiltrated lymph nodes, EBRT was also performed. RESULTS: In 30/53 patients (56.6%) breast-conserving surgery could be performed. The overall histopathologic response rate was 96.2% with a complete remission in 28.3% of patients. 49/53 patients were evaluable for follow-up. After a median of 58 months (45-72 months), one patient showed a mild fibrosis of the breast tissue, three patients had mild to moderate lymphatic edema of the arm. 6/49 (12.2%) patients died of distant metastases, 4/49 (8.2%) were alive with disease, and 39/49 (79.6%) were free from disease. Local recurrence was observed in only one case (2%) 40 months after primary therapy. After mastectomy, this patient is currently free from disease. CONCLUSION: The combination of interstitial HDR brachytherapy and chemotherapy is a well-tolerated and effective neoadjuvant treatment in patients with breast cancer. Compared to EBRT, treatment time is short. Postoperative EBRT of the whole breast -- if necessary -- is still possible after neoadjuvant brachytherapy. Even though the number of patients does not permit definite conclusions, the results are promising regarding survival and the very low rate of local recurrences.

Progress on BIG 1-02/IBCSG 27-02/NSABP B-37, a prospective randomized trial evaluating chemotherapy after local therapy for isolated locoregional recurrences of breast cancer

BACKGROUND: The utility of chemotherapy for women who experience a locoregional recurrence after primary treatment of early breast cancer remains an open question. An international collaborative trial is being conducted by the Breast International Group (BIG), the International Breast Cancer Study Group (IBCSG), and the National Surgical Adjuvant Breast and Bowel Project (NSABP) to determine the effectiveness of cytotoxic therapy for these patients, either alone or in addition to selective use of hormonal therapy and trastuzumab. METHODS: The trial population includes women who have had a previous diagnosis of invasive breast cancer treated by mastectomy or breast-conserving surgery, but subsequently develop an isolated local and/or regional ipsilateral invasive recurrence. Excision of all macroscopic tumor without evidence of systemic disease is required for study entry. Patients are randomized to receive chemotherapy or no chemotherapy; type of chemotherapy is not protocol-specified. Radiation, hormonal therapy, and trastuzumab are given as appropriate. The primary endpoint is disease-free survival (DFS). Quality-of-life measurements are collected at baseline, and then at 9 and 12 months. The accrual goal is 977 patients. RESULTS: This report describes the characteristics of the first 99 patients. Sites of recurrence at study entry were: breast (56%), mastectomy scar/chest wall (35%), and regional lymph nodes (9%). Two-thirds of patients have estrogen-receptor-positive recurrences. CONCLUSION: This is the only trial actively investigating the question of "adjuvant" chemotherapy in locally recurrent breast cancer. The case mix of accrual to date indicates a broad representation of this patient population.

A randomized clinical trial of adjuvant chemotherapy for radically resected locoregional relapse of breast cancer: IBCSG 27-02, BIG 1-02, and NSABP B-37

In this phase III, multinational, randomized trial, the International Breast Cancer Study Group, Breast International Group, and the National Surgical Adjuvant Breast and Bowel Project will attempt to define the effectiveness of cytotoxic therapy for patients with locoregional recurrence of breast cancer. We will evaluate whether chemotherapy prolongs disease-free survival and, secondarily, whether its use improves overall survival and systemic disease-free survival. Quality of life measurements will be monitored during the first 12 months of the study. Women who have had a previous diagnosis of invasive breast cancer treated by mastectomy or breast-conserving surgery and who have undergone complete surgical excision of all macroscopic disease but who subsequently develop isolated local and/or regional ipsilateral invasive recurrence are eligible. Patients are randomized to observation/no adjuvant chemotherapy or to adjuvant chemotherapy; all suitable patients receive radiation, hormonal, and trastuzumab therapy. Radiation therapy is recommended for patients who have not received previous adjuvant radiation therapy but is required for those with microscopically positive margins. The radiation field must encompass the tumor bed plus a surrounding margin to a dose of >or= 40 Gy. Radiation therapy will be administered before, during, or after chemotherapy. All women with estrogen receptor-positive and/or progesterone receptor-positive recurrence must receive hormonal therapy, with the agent and duration to be determined by the patient's investigator. Adjuvant trastuzumab therapy is permitted for those with HER2- positive tumors, provided that intent to treat is declared before randomization. Although multidrug regimens are preferred, the agents, doses, and use of supportive therapy are at the discretion of the investigator.

Percutaneous access of the epicardial space for mapping ventricular and supraventricular arrhythmias in patients with and without prior cardiac surgery

There is a paucity of data on the success rates of achieving percutaneous epicardial access in different groups of patients.

Early 4-Week Cardiac Rehabilitation Exercise Training in Elderly Patients After Heart Surgery

The aim of this study was to assess the effects on exercise performance of supplementing a standard cardiac rehabilitation program with additional exercise programming compared to the standard cardiac rehabilitation program alone in elderly patients after heart surgery.

Sciatic neuropathy after body contouring surgery in massive weight loss patients

To date, obesity affects a substantial population in industrialised countries. Due to the increased awareness of obesity-related morbidity, efficient dietary regimens and the recent successes with bariatric surgery, there is now a high demand for body contouring surgery to correct skin abundancies after massive weight loss. The known risks for this type of surgery are mainly wound-healing complications, and, more rarely, thromboembolic or respiratory complications. We present two female patients (23 and 39 years of age) who, in spite of standard positioning and precautions, developed sciatic neuropathy after combined body contouring procedures, including abdominoplasty and inner thigh lift. Complete functional loss of the sciatic nerve was found by clinical and electroneurographic examination on the left side in patient one and bilaterally in patient two. Full nerve conductance recovery was obtained after 6 months in both patients. Although the occurrence of spontaneous neuropathies after heavy weight loss is well documented, this is the first report describing the appearance of such a phenomenon following body contouring surgery. One theoretical explanation may be the compression of the nerve during the semirecumbent positioning combined with hip flexion and abduction, which was required for abdominal closure and simultaneous access to the inner thighs. We advise to avoid this positioning and to include the risk of sciatic neuropathy in the routine preoperative information of patients scheduled for body contouring surgery after heavy weight loss.

Iatrogenic orifice transluminal endoscopic surgery (IOTES): managing uterine perforations at operative hysteroscopy

To prove safety and feasibility of an intra-abdominal endoscopic evaluation via an iatrogenic uterine perforation that occurred during operative hysteroscopy.

Nutritional risk is a clinical predictor of postoperative mortality and morbidity in surgery for colorectal cancer

This study investigated whether nutritional risk scores applied at hospital admission predict mortality and complications after colorectal cancer surgery.

Perioperative metabolic changes in patients undergoing cardiac surgery

Perioperative metabolic changes in cardiac surgical patients are not only induced by tissue injury and extracorporeal circulation per se: the systemic inflammatory response to surgical trauma and extracorporeal circulation, perioperative hypothermia, cardiovascular and neuroendocrine responses, and drugs and blood products used to maintain cardiovascular function and anesthesia contribute to varying degrees. The pathophysiologic changes include increased oxygen consumption and energy expenditure; increased secretion of adrenocorticotrophic hormone, cortisol, epinephrine, norepinephrine, insulin, and growth hormone; and decreased total tri-iodothyronine levels. Easily measurable metabolic consequences of these changes include hyperglycemia, hyperlactatemia, increased aspartate, glutamate and free fatty acid concentrations, hypokalemia, increased production of inflammatory cytokines, and increased consumption of complement and adhesion molecules. Nutritional risk before elective cardiac surgery-defined as preoperative unintended pathologic weight loss/low amount of food intake in the preceding week or low body mass index-is related to adverse postoperative outcome. Improvements in surgical techniques, anesthesia, and perioperative management have been designed to minimize the stressful stimulus to catabolism, thereby slowing the wasting process to the point where much less nutrition is required to meet metabolic requirements. Early nutrition in cardiac surgery is safe and well tolerated.

Clinical results with two different methods of root-end preparation and filling in apical surgery: mineral trioxide aggregate and adhesive resin composite

INTRODUCTION: The aim of apical surgery is to hermetically seal the root canal system after root-end resection, thereby enabling periradicular healing. The objective of this nonrandomized prospective clinical study was to report results of 2 different root-end preparation and filling methods, ie, mineral trioxide aggregate (MTA) and an adhesive resin composite (Retroplast). METHODS: The study included 353 consecutive cases with endodontic lesions limited to the periapical area. Root-end cavities were prepared with sonic microtips and filled with MTA (n = 178), or alternatively, a shallow concavity was prepared in the cut root face, with subsequent placement of an adhesive resin composite (Retroplast) (n = 175). Patients were recalled after 1 year. Cases were defined as healed when no clinical signs or symptoms were present and radiographs demonstrated complete or incomplete (scar tissue) healing of previous radiolucencies. RESULTS: The overall rate of healed cases was 85.5%. MTA-treated teeth demonstrated a significantly (P = .003) higher rate of healed cases (91.3%) compared with Retroplast-treated teeth (79.5%). Within the MTA group, 89.5%-100% of cases were classified as healed, depending on the type of treated tooth. In contrast, more variable rates ranging from 66.7%-100% were found in the Retroplast group. In particular, mandibular premolars and molars demonstrated considerably lower rates of healed cases when treated with Retroplast. CONCLUSIONS: MTA can be recommended for root-end filling in apical surgery, irrespective of the type of treated tooth. Retroplast should be used with caution for root-end sealing in apical surgery of mandibular premolars and molars.

Haemostatic effect and tissue reactions of methods and agents used for haemorrhage control in apical surgery

To compare the haemostatic effect and tissue reactions of different agents and methods used for haemorrhage control in apical surgery.

A randomized, controlled clinical trial on the clinical, microbiological, and staining effects of a novel 0.05% chlorhexidine/herbal extract and a 0.1% chlorhexidine mouthrinse adjunct to periodontal surgery

BACKGROUND: Chlorhexidine (CHX) rinsing after periodontal surgery is common. We assessed the clinical and microbiological effects of two CHX concentrations following periodontal surgery. MATERIALS AND METHODS: In a randomized, controlled clinical trial, 45 subjects were assigned to 4 weeks rinsing with a 0.05 CHX/herbal extract combination (test) or a 0.1% CHX solution. Clinical and staining effects were studied. Subgingival bacteria were assessed using the DNA-DNA checkerboard. Statistics included parametric and non-parametric tests (p<0001 to declare significance at 80% power). RESULTS: At weeks 4 and 12, more staining was found in the control group (p<0.05 and p<0.001, respectively). A higher risk for staining was found in the control group (crude OR: 2.3:1, 95% CI: 1.3 to 4.4, p<0.01). The absolute staining reduction in the test group was 21.1% (9 5% CI: 9.4-32.8%). Probing pocket depth (PPD) decreases were significant (p<0.001) in both groups and similar (p=0.92). No rinse group differences in changes of bacterial counts for any species were found between baseline and week 12. CONCLUSIONS: The test CHX rinse resulted in less tooth staining. At the study endpoint, similar and high counts of periodontal pathogens were found.