A systematic review of outcomes reported inpediatric perioperative research: A report from the Pediatric Perioperative Outcomes Group.

The Pediatric Perioperative Outcomes Group (PPOG) is an international collaborative of clinical investigators and clinicians within the subspecialty of pediatric anesthesiology and perioperative care which aims to use COMET (Core Outcomes Measures in Effectiveness Trials) methodology to develop core outcome setsfor infants, children and young people that are tailored to the priorities of the pediatric surgical population.Focusing on four age-dependent patient subpopulations determined a priori for core outcome set development: i) neonates and former preterm infants (up to 60 weeks postmenstrual age); ii) infants (>60 weeks postmenstrual age - <1 year); iii) toddlers and school age children (>1-<13 years); and iv) adolescents (>13-<18 years), we conducted a systematic review of outcomes reported in perioperative studies that include participants within age-dependent pediatric subpopulations. Our review of pediatric perioperative controlled trials published from 2008 to 2018 identified 724 articles reporting 3192 outcome measures. The proportion of published trials and the most frequently reported outcomes varied across pre-determined age groups. Outcomes related to patient comfort, particularly pain and analgesic requirement, were the most frequent domain for infants, children and adolescents. Clinical indicators, particularly cardiorespiratory or medication-related adverse events, were the most common outcomes for neonates and infants < 60 weeks and were the second most frequent domain at all other ages. Neonates and infants <60 weeks of age were significantly under-represented in perioperative trials. Patient-centered outcomes, heath care utilization, and bleeding/transfusion related outcomes were less often reported. In most studies, outcomes were measured in the immediate perioperative period, with the duration often restricted to the post-anesthesia care unit or the first 24 postoperative hours. The outcomes identified with this systematic review will be combined with patient centered outcomes identified through a subsequent stakeholder engagement study to arrive at a core outcome set for each age-specific group.

Anesthesia for children with pericardial effusion: a case series.

OBJECTIVES AND AIMS: To review the anesthetic management of children requiring surgical intervention for pericardial effusion, determine the nature and frequency of complications and define risk factors that predict perioperative risk. BACKGROUND: Anesthesia in the presence of a pericardial effusion may be associated with significant hemodynamic compromise particularly during induction. However, the literature specifically concerning children is limited to a single-case report. METHODS: A retrospective case review of children undergoing general anesthesia for surgical treatment for pericardial effusion between 1999 and 2008 at a single institution. RESULTS: Sixty-five children underwent 79 general anesthetics for surgical treatment for pericardial effusion. Median age was 4 years (2 weeks-16 years), and median weight 15 kg (range, 2.5-96 kg). Fifty-five children (84%) developed effusions following cardiac surgery. The commonest induction agent was ketamine (25/65, 38%), and the majority of children (52/65, 80%) were intubated and ventilated for the procedure. Seven children (11%) suffered from eight major complications, and 14 children (22%) suffered from a minor complication. Major complications were more common in children with preoperative tachypnoea (P = 0.01) and cardiac tamponade on preoperative echocardiogram (ECHO) (P = 0.001). Preoperative hypoxia had a sensitivity of 92% and a positive likelihood ratio of 5.2 (95% CI 1.5-17.5) for predicting all complications. CONCLUSIONS: Anesthesia for pericardial effusion in children was associated with an adverse physiological event in one-third of children. Major complications may be predicted by preoperative tachypnoea and cardiac tamponade on preoperative ECHO, and all complications may be predicted by preoperative hypoxia. The anesthetic technique included a variety of induction agents, and we cannot recommend a particular approach.

Mammographic density and the risk of breast cancer recurrence after breast-conserving surgery.

BACKGROUND: Women with invasive breast cancer who are treated with breast-conserving surgery and radiotherapy face a cumulative risk of local disease recurrence of approximately 10% at 10 years. To the authors' knowledge, the role of mammographic density as a risk factor for the development of local recurrence has not been thoroughly evaluated to date. METHODS: Medical records were reviewed for 335 patients who underwent breast-conserving surgery for invasive breast cancer and for whom a pretreatment mammogram was available. Information was recorded concerning mammographic density as well as tumor features, patient characteristics, and adjuvant treatments received. Patients were categorized for mammographic density based on the Wolfe classification as either low (<25% density), intermediate (25-50% density), or high (>50% density). A multivariate survival analysis was conducted using the Cox proportional hazards model with local disease recurrence as the primary endpoint. RESULTS: Patients in the high mammographic density group experienced a much greater risk of local disease recurrence compared with women with the least dense breasts (10-year actuarial risks: 21% vs 5%; hazards ratio [HR], 5.7 [95% confidence interval, 1.6-20; P=.006]). The difference in the rates of disease recurrence at 10 years was pronounced for women who did not receive radiotherapy (40% vs 0% for patients with >50% density and <25% density, respectively; P<.0001). CONCLUSIONS: Mammographic breast density is an important risk factor for local breast cancer recurrence among women not receiving breast irradiation. Mammographic density should be taken into consideration when stratifying patients for clinical trials of partial breast radiotherapy. If confirmed, mammographic density might be used to help determine which patients might benefit from radiotherapy.

Time to disease recurrence in basal-type breast cancers: effects of tumor size and lymph node status.

BACKGROUND: : Basal-like breast cancers are a subgroup of breast cancers defined by the absence of staining for estrogen-receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER-2/neu) and by positive staining for the cytokeratins (CKs) expressed in the myoepithelial cells of the ducts and lobules (CK5/CK6, CK14) and for epidermal growth factor receptor (EGFR). This class of tumors has an unusually aggressive course, and it is not clear whether conventional prognostic factors for breast cancers also predict outcome for patients who have the basal phenotype. METHODS: : A panel of 962 breast cancers was stained for 5 markers (ER, PR, HER-2/neu, CK5/CK6, and EGFR). The patients were followed for clinical outcomes for up to 15 years from diagnosis, and the rates of distant disease recurrence and death were compared by tumor size (< or =2 cm or >2 cm) and by lymph node status within the subgroups of women with basal and nonbasal cancers. RESULTS: : Of the 962 women with breast cancer, 116 cancers were basal (12%), 845 were nonbasal (88%), and 1 could not be classified as either basal or nonbasal and was excluded. In total, 426 tumors measured < or =2 cm (45%), and 530 tumors measured >2 cm (55%). Among women with nonbasal cancers, large tumor size was an adverse prognostic factor. Among women with basal cancers, a transient adverse effect of size on disease recurrence was observed; however, after 10 years, mortality rates were equal for women with small tumors and women with large tumors. CONCLUSIONS: : Among women with basal breast cancers, the long-term prognosis was similar for women with large tumors and women with small tumors. However, women with large basal tumors appeared to develop recurrent disease sooner. Cancer 2009. (c) 2009 American Cancer Society.

Patterns of recurrence in the basal and non-basal subtypes of triple-negative breast cancers.

Traditional prognostic markers for breast cancer include estrogen receptor (ER), progesterone receptor (ER) and HER2/neu. Negative staining for these three markers defines the 'triple-negative' phenotype. By adding markers for cytokeratin 5/6 and EGFR, triple-negative breast cancers can be divided into 'basal-like' and 'normal-like' subgroups. We conducted immuno-staining on a panel of 958 patients with breast cancer, using all five markers and we followed the patients for distal recurrence and death. We compared rates of distal recurrence in the basal-like and normal-like subgroups with that of women with ER-positive breast cancer. Only 16 of 958 women had normal-like breast cancers. These cancers resembled basal-like cancers in that they had a high proliferative index, but the women with normal-like breast cancers resembled ER-positive women in terms of distant recurrence. The addition of CK5/6 and EGFR to the standard panel (ER/PR/HER2/neu) defines a small subgroup of women with normal-like breast cancer. The prognosis of these women may be superior to that of basal-like breast cancers but firm conclusions cannot be made.

Pattern of metastatic spread in triple-negative breast cancer.

PURPOSE: The prognosis of women with triple-negative breast cancers (defined as cancers that are estrogen receptor-negative, progesterone receptor-negative and HER2/neu negative) is poor, compared to women with other subtypes of breast cancer. It is proposed that the underlying difference in recurrence rates may be explained in part by different routes of metastatic spread. EXPERIMENTAL DESIGN: We studied a cohort of 1608 patients diagnosed with breast cancer, diagnosed between January 1987 and December 1997 at Women's College Hospital in Toronto. Triple-negative breast cancers were defined as those that were estrogen receptor-negative, progesterone receptor-negative and HER2/neu-negative. We compared the incidence rates of metastatic spread to bone and to other (non-bone) organs in women with triple-negative and other forms of breast cancer. RESULTS: Of the 1,608 patients, 180 (11.2%) had triple-negative breast cancer. The 1608 women were followed for a median of 9.0 years (range 0.1-19 years). Compared to other patients, those with triple-negative breast cancer had an increased likelihood of distant recurrence over the study period (adjusted hazard ratio (HR) 1.9; 95% CI: 1.5-2.5, P < 0.0001). The relatively poor prognosis was apparent in the five years after diagnosis (HR 2.9; 95% CI: 2.1-3.9; P = 0.0001) but not thereafter (HR 0.5; 95% CI: 0.2-1.1; P = 0.07). In particular, women with triple-negative breast cancer were four times more likely to experience a visceral metastasis within five years of diagnosis than those with other types of cancer (HR 4.0; 95% CI: 2.7-5.9; P < 0.0001). The rates of bone metastases were comparable for triple-negative and for other forms of cancer in this time period (HR 0.8; 95% CI: 0.4-1.6 P = 0.5). CONCLUSIONS: The excess risk of distant recurrence in triple-negative breast cancers, versus other forms of cancer, is attributable in large part to an excess of visceral metastases in the first five years following diagnosis.

Triple-negative breast cancer: clinical features and patterns of recurrence.

PURPOSE: To compare the clinical features, natural history, and outcomes for women with "triple-negative" breast cancer with women with other types of breast cancer. EXPERIMENTAL DESIGN: We studied a cohort of 1,601 patients with breast cancer, diagnosed between January 1987 and December 1997 at Women's College Hospital in Toronto. Triple-negative breast cancers were defined as those that were estrogen receptor negative, progesterone receptor negative, and HER2neu negative. The prognostic significance of triple-negative breast cancer was explored. RESULTS: The median follow-up time of the 1,601 women was 8.1 years. One hundred and eighty of 1,601 patients (11.2%) had triple-negative breast cancer. Compared with other women with breast cancer, those with triple-negative breast cancer had an increased likelihood of distant recurrence (hazard ratio, 2.6; 95% confidence interval, 2.0-3.5; P < 0.0001) and death (hazard ratio, 3.2; 95% confidence interval, 2.3-4.5; P < 0.001) within 5 years of diagnosis but not thereafter. The pattern of recurrence was also qualitatively different; among the triple-negative group, the risk of distant recurrence peaked at approximately 3 years and declined rapidly thereafter. Among the "other" group, the recurrence risk seemed to be constant over the period of follow-up. CONCLUSIONS: Triple-negative breast cancers have a more aggressive clinical course than other forms of breast cancer, but the adverse effect is transient.

The role of reexcision for positive margins in optimizing local disease control after breast-conserving surgery for cancer.

One of the most important factors associated with local recurrence after lumpectomy in breast cancer patients is the status of the surgical margin. Standard surgical practice is to obtain clear margins even if this requires a second surgical procedure. It is assumed that reexcision to achieve clear margins when positive margins are present at initial excision is as effective as complete tumor removal at a single procedure; however, the efficacy of reexcision in this context has not been well studied. A retrospective search of the Henrietta Banting Breast Centre database from 1987 to 1997 identified 1430 patients who underwent lumpectomy for invasive breast cancer: 1225 patients (group A) had negative margins at the initial surgery and 152 patients (group B) underwent one or more reexcisions to achieve negative margins. Fifty-three patients had positive margins at final surgery, but no reexcision was done (group C). Logistic regression was used to identify factors that were predictive of a positive margin; predictors of local recurrence in women whose tumors were completely resected were determined using Cox's proportional hazards model. Patients in groups A, B, and C differed with respect to mean age at diagnosis (58 years, 51 versus, and 56 years, respectively, p < 0.0001), mean tumor size (19 mm, 16 mm, and 26 mm, respectively, p < 0.0001), node positivity (30%, 22%, and 41%, respectively, p = 0.004), and the presence of a ductal carcinoma in situ (DCIS) component (60%, 64%, and 79%, respectively, p = 0.007). The mean follow-up period was similar for the three groups (8 years, 8 years, and 9 years, respectively, p = 0.17). Young age was the only variable predictive of positive margins. Among patients undergoing complete tumor excision, there was a suggestion of a higher 10 year local recurrence rate in reexcision group B, but the difference did not reach statistical significance (11.6% versus 16.6%, p = 0.11). Cox's multivariate regression analyses identified older age, smaller tumor size, receiving radiation therapy, and tamoxifen use as significantly decreasing the rate of local recurrence in patients with negative margins at initial surgery or after reexcision. Our data confirm the results of previous studies indicating that young age is an independent predictor of positive margins after lumpectomy for invasive breast cancer. The only independent predictor of local recurrence in our study cohort was large tumor size. There was a trend toward a higher local recurrence rate if more than one procedure was required to secure clear margins, although this effect was not independent of other factors. Reexcision to clear involved margins is an important surgical intervention for both younger and older women.