Radiotherapy or surgery of the axilla after a positive sentinel node in breast cancer (EORTC 10981-22023 AMAROS): a randomised, multicentre, open-label, phase 3 non-inferiority trial.

BACKGROUND: If treatment of the axilla is indicated in patients with breast cancer who have a positive sentinel node, axillary lymph node dissection is the present standard. Although axillary lymph node dissection provides excellent regional control, it is associated with harmful side-effects. We aimed to assess whether axillary radiotherapy provides comparable regional control with fewer side-effects. METHODS: Patients with T1-2 primary breast cancer and no palpable lymphadenopathy were enrolled in the randomised, multicentre, open-label, phase 3 non-inferiority EORTC 10981-22023 AMAROS trial. Patients were randomly assigned (1:1) by a computer-generated allocation schedule to receive either axillary lymph node dissection or axillary radiotherapy in case of a positive sentinel node, stratified by institution. The primary endpoint was non-inferiority of 5-year axillary recurrence, considered to be not more than 4% for the axillary radiotherapy group compared with an expected 2% in the axillary lymph node dissection group. Analyses were by intention to treat and per protocol. The AMAROS trial is registered with ClinicalTrials.gov, number NCT00014612. FINDINGS: Between Feb 19, 2001, and April 29, 2010, 4823 patients were enrolled at 34 centres from nine European countries, of whom 4806 were eligible for randomisation. 2402 patients were randomly assigned to receive axillary lymph node dissection and 2404 to receive axillary radiotherapy. Of the 1425 patients with a positive sentinel node, 744 had been randomly assigned to axillary lymph node dissection and 681 to axillary radiotherapy; these patients constituted the intention-to-treat population. Median follow-up was 6·1 years (IQR 4·1-8·0) for the patients with positive sentinel lymph nodes. In the axillary lymph node dissection group, 220 (33%) of 672 patients who underwent axillary lymph node dissection had additional positive nodes. Axillary recurrence occurred in four of 744 patients in the axillary lymph node dissection group and seven of 681 in the axillary radiotherapy group. 5-year axillary recurrence was 0·43% (95% CI 0·00-0·92) after axillary lymph node dissection versus 1·19% (0·31-2·08) after axillary radiotherapy. The planned non-inferiority test was underpowered because of the low number of events. The one-sided 95% CI for the underpowered non-inferiority test on the hazard ratio was 0·00-5·27, with a non-inferiority margin of 2. Lymphoedema in the ipsilateral arm was noted significantly more often after axillary lymph node dissection than after axillary radiotherapy at 1 year, 3 years, and 5 years. INTERPRETATION: Axillary lymph node dissection and axillary radiotherapy after a positive sentinel node provide excellent and comparable axillary control for patients with T1-2 primary breast cancer and no palpable lymphadenopathy. Axillary radiotherapy results in significantly less morbidity. FUNDING: EORTC Charitable Trust.

Costs of relaparotomy on-demand versus planned relaparotomy in patients with severe peritonitis: an economic evaluation within a randomized controlled trial.

INTRODUCTION: Results of the first randomized trial comparing on-demand versus planned-relaparotomy strategy in patients with severe peritonitis (RELAP trial) indicated no clear differences in primary outcomes. We now report the full economic evaluation for this trial, including detailed methods, nonmedical costs, further differentiated cost calculations, and robustness of different assumptions in sensitivity analyses. METHODS: An economic evaluation was conducted from a societal perspective alongside a randomized controlled trial in 229 patients with severe secondary peritonitis and an acute physiology and chronic health evaluation (APACHE)-II score >or=11 from two academic and five regional teaching hospitals in the Netherlands. After the index laparotomy, patients were randomly allocated to an on-demand or a planned-relaparotomy strategy. Primary resource-utilization data were used to estimate mean total costs per patient during the index admission and after discharge until 1 year after the index operation. Overall differences in costs between the on-demand relaparotomy strategy and the planned strategy, as well as relative differences across several clinical subgroups, were evaluated. RESULTS: Costs were substantially lower in the on-demand group (mean, 65,768 euro versus 83,450 euro per patient in the planned group; mean absolute difference, 17,682 euro; 95% CI, 5,062 euro to e29,004 euro). Relative differences in mean total costs per patient (approximately 21%) were robust to various alternative assumptions. Planned relaparotomy consistently generated more costs across the whole range of different courses of disease (quick recovery and few resources used on one end of the spectrum; slow recovery and many resources used on the other end). This difference in costs between the two surgical strategies also did not vary significantly across several clinical subgroups. CONCLUSIONS: The reduction in societal costs renders the on-demand strategy a more-efficient relaparotomy strategy in patients with severe peritonitis. These differences were found across the full range of healthcare resources as well as across patients with different courses of disease. TRIAL REGISTRATION: ISRCTN51729393.

Temporary end ileostomy with subcutaneously buried efferent limb: results and potential advantages.

PURPOSE: To evaluate the results of a modified technique of creating a defunctioning end ileostomy. METHODS: Medical records of all consecutive patients with a defunctioning end ileostomy with buried efferent limb operated at our hospital between January 2000 and December 2007 were reviewed. The defunctioning end ileostomy with buried efferent limb is created by closing the distal limb and positioning it in the subcutis. Parameters studied were: stomal and reversal related complications. RESULTS: 66 patients were included. Between construction and closure of the stoma, a total of 21 patients (31.8%) developed stoma-related complications. In 1 patient (1.5%) high output occurred, in 6 (9%) stomal retraction and in 4 (6.1%) a parastomal hernia occurred. Peristomal skin problems were observed in 14 patients (21.2%) in the early postoperative period, decreasing to 6 patients (9.1%) after 3 weeks. In 1 patient, stoma closure could not be performed through a local approach and formal laparotomy was necessary. Complications of loop ileostomy as reported in the literature show relatively high rates of peristomal skin and leakage problems. CONCLUSIONS: Our results suggest that end ileostomy with subcutaneous buried efferent limb offers advantages over loop ileostomy with regard to the risk of developing peristomal skin and leakage problems.

Health related quality of life six months following surgical treatment for secondary peritonitis--using the EQ-5D questionnaire.

BACKGROUND: To compare health related quality of life (HR-QoL) in patients surgically treated for secondary peritonitis to that of a healthy population. And to prospectively identify factors associated with poorer (lower) HR-QoL. DESIGN: A prospective cohort of secondary peritonitis patients was mailed the EQ-5D and EQ-VAS 6-months following initial laparotomy. SETTING: Multicenter study in two academic and seven regional teaching hospitals. PATIENTS: 130 of the 155 eligible patients (84%) responded to the HR-QoL questionnaires. RESULTS: HR-QoL was significantly worse on all dimensions in peritonitis patients than in a healthy reference population. Peritonitis characteristics at initial presentation were not associated with HR-QoL at six months. A more complicated course of the disease leading to longer hospitalization times and patients with an enterostomy had a negative impact on the mobility (p = 0.02), self-care (p < 0.001) and daily activities: (p = 0.01). In a multivariate analysis for the EQ-VAS every doubling of hospital stay decreases the EQ-VAS by 3.8 points (p = 0.015). Morbidity during the six-month follow-up was not found to be predictive for the EQ-5D or EQ-VAS. CONCLUSION: Six months following initial surgery, patients with secondary peritonitis report more problems in HR-QoL than a healthy reference population. Unfavorable disease characteristics at initial presentation were not predictive for poorer HR-QoL, but a more complicated course of the disease was most predictive of HR-QoL at 6 months.

Comparison of on-demand vs planned relaparotomy strategy in patients with severe peritonitis: a randomized trial.

CONTEXT: In patients with severe secondary peritonitis, there are 2 surgical treatment strategies following an initial emergency laparotomy: planned relaparotomy and relaparotomy only when the patient's condition demands it ("on-demand"). The on-demand strategy may reduce mortality, morbidity, health care utilization, and costs. However, randomized trials have not been performed. OBJECTIVE: To compare patient outcome, health care utilization, and costs of on-demand and planned relaparotomy. DESIGN, SETTING, AND PATIENTS: Randomized, nonblinded clinical trial at 2 academic and 5 regional teaching hospitals in the Netherlands from November 2001 through February 2005. Patients had severe secondary peritonitis and an Acute Physiology and Chronic Health Evaluation (APACHE-II) score of 11 or greater. INTERVENTION: Random allocation to on-demand or planned relaparotomy strategy. MAIN OUTCOME MEASURES: The primary end point was death and/or peritonitis-related morbidity within a 12-month follow-up period. Secondary end points included health care utilization and costs. RESULTS: A total of 232 patients (116 on-demand and 116 planned) were randomized. One patient in the on-demand group was excluded due to an operative diagnosis of pancreatitis and 3 in each group withdrew or were lost to follow-up. There was no significant difference in primary end point (57% on-demand [n = 64] vs 65% planned [n = 73]; P = .25) or in mortality alone (29% on-demand [n = 32] vs 36% planned [n = 41]; P = .22) or morbidity alone (40% on-demand [n = 32] vs 44% planned [n = 32]; P = .58). A total of 42% of the on-demand patients had a relaparotomy vs 94% of the planned relaparotomy group. A total of 31% of first relaparotomies were negative in the on-demand group vs 66% in the planned group (P <.001). Patients in the on-demand group had shorter median intensive care unit stays (7 vs 11 days; P = .001) and shorter median hospital stays (27 vs 35 days; P = .008). Direct medical costs per patient were reduced by 23% using the on-demand strategy. CONCLUSION: Patients in the on-demand relaparotomy group did not have a significantly lower rate of death or major peritonitis-related morbidity compared with the planned relaparotomy group but did have a substantial reduction in relaparotomies, health care utilization, and medical costs. TRIAL REGISTRATION: http://isrctn.org Identifier: ISRCTN51729393.

Impact of parathyroidectomy for primary hyperparathyroidism on quality of life: A case-control study using Short Form Health Survey 36.

BACKGROUND: Physical and mental complaints are common in patients with primary hyperparathyroidism (PHPT) and negatively impact quality of life (QOL). Subjective symptoms in current guidelines are not considered an indication for surgery. The purpose of this study was to assess the effect of parathyroidectomy on QOL in patients with PHPT. METHODS: This multicenter case-control study investigated preoperative and postoperative QOL scores in patients operated for PHPT, measured with the Short Form Health Survey-36 (SF-36) questionnaire. Results were compared with patients undergoing a hemithyroidectomy, the control group. RESULTS: Fifty-two patients and 49 controls were included. Patients with PHPT had significantly lower QOL scores preoperatively and improved significantly after successful surgical treatment. Postoperatively, no differences were observed between the 2 groups. CONCLUSION: QOL was significantly lower in patients with untreated PHPT. Surgical treatment was associated with a significant increase in QOL. Decreased QOL should also be considered as an indicator for surgical treatment in patients with PHPT. © 2016 Wiley Periodicals, Inc. Head Neck 38:1213-1220, 2016.

Malignant breast tumor phospholipid profiles using (31)P magnetic resonance.

Biochemical markers improve the classification and staging of breast cancer and may refine management decisions if it can be shown that they correlate with accepted prognostic factors or patient outcome. Using phosphorus-31 magnetic resonance spectroscopy ((31)P MRS), we determined the phospholipid content of 43 malignant breast tumors, correlating the profiles with specific histopathologic and clinical features and hormone receptor status. Among the 14 phospholipids identified, the mean mole percentage of sphingomyelin, phosphatidylcholine, phosphatidylserine, phosphatidic acid, phosphatidylglycerol, and alkylacylphosphatidylcholine predicted cellular infiltration, infiltration type, elastosis, lymphatic invasion, perineural invasion, necrosis, and estrogen receptor positivity. (31)P MRS phospholipid profile data provide statistical correlations among histologic features and molecules known to play important roles in cellular communication, regulation, and processes unique to malignant tissues.

Current surgical treatment of diverticular disease in The Netherlands.

AIM: To evaluate the development of diagnostic tools, indications for surgery and treatment modalities concerning diverticular disease (DD) in The Netherlands. METHODS: Data were collected from 100 patients who underwent surgery for DD in three Dutch hospitals. All hospitals used the same standardized database. The collected data included patient demographics, patient history, type of surgery and complications. Patients were divided into two groups, one undergoing elective surgery (elective group) and the other undergoing acute surgery (acute group). RESULTS: Two hundred and ninety-nine patients were admitted between 2000 and 2007. One hundred and seventy-eight patients underwent acute surgery and 121 patients received elective operations. The median age of the 121 patients was 69 years (range: 28-94 years), significantly higher in acute patients (P = 0.010). Laparoscopic resection was performed in 31% of elective patients. In the acute setting, 61% underwent a Hartmann procedure. The overall morbidity and mortality were 51% and 10%, and 60% and 16% in the acute group, which were significantly higher than in the elective group (36% and 1%). Only 35% of the temporary ostomies were restored. CONCLUSION: This study gives a picture of current surgical practice for DD in The Netherlands. New developments are implemented in daily practice, resulting in acceptable morbidity and mortality rates.

Similar efficacy for ovarian ablation compared with cyclophosphamide, methotrexate, and fluorouracil: from a randomized comparison of premenopausal patients with node-positive, hormone receptor-positive breast cancer.

PURPOSE: To compare the efficacy of ovarian ablation versus chemotherapy in early breast cancer patients with hormone receptor-positive disease. PATIENTS AND METHODS: We conducted an open, randomized, multicenter trial including premenopausal breast cancer patients with hormone receptor-positive tumors and either axillary lymph node metastases or tumors with a size of 5 cm or more. Patients were randomly assigned to ovarian ablation by irradiation or to nine courses of chemotherapy with intravenous cyclophosphamide, methotrexate, and fluorouracil (CMF) administered every 3 weeks. RESULTS: Between 1990 and May 1998, 762 patients were randomly assigned, and the present analysis is based on 358 first events. After a median follow-up time of 8.5 years, the unadjusted hazard ratio for disease-free survival in the ovarian ablation group compared with the CMF group was 0.99 (95% CI, 0.81 to 1.22). After a median follow-up time of 10.5 years, overall survival (OS) was similar in the two groups, with a hazard ratio of 1.11 (95% CI, 0.88 to 1.42) for the ovarian ablation group compared with the CMF group. CONCLUSION: In this study, ablation of ovarian function in premenopausal women with hormone receptor-positive breast cancer had a similar effect to CMF on disease-free and OS. No significant interactions were demonstrated between treatment modality and hormone receptor content, age, or any of the well-known prognostic factors.