Case report: ventricular fibrillation and cardiac arrest provoked by forward bending in adolescent with severe pectus excavatum.

BACKGROUND: Life-threatening arrhythmias have been reported in patients with severe pectus excavatum in absence of other cardiac abnormalities. Literature is scarce regarding diagnosis, cause and management of this problem, particularly regarding the question as to whether the placement of an implantable cardioverter-defibrillator (ICD) is necessary. CASE SUMMARY: A 19-year-old male patient with severe pectus excavatum was scheduled for elective surgical correction. During forward bending for epidural catheter placement, syncope and ventricular fibrillation (VF) occurred resulting in cardiac arrest. After successful cardiopulmonary resuscitation, extensive analysis was performed and showed no cause for VF other than cardiac compression (particularly of the left atrium, right atrium, and ventricle to a lesser degree) due to severe pectus excavatum. Postponed correction by modified Ravitch was performed without ICD placement, with an uneventful post-operative recovery. Eighteen months after surgery, the patient remains well. Upon specific request, he did remember dizzy spells when tying shoelaces. He always considered this unremarkable. DISCUSSION: In severe pectus excavatum with cardiac compression, forward bending can decrease central venous return and cardiac output, causing hypotension, arrhythmia, and cardiac arrest. In absence of structural or electric abnormalities, cardiac compression by severe pectus excavatum was considered a reversible cause of VF and ICD placement unnecessary. Patients with cardiac compression due to severe pectus excavatum may report pre-existing postural symptoms upon specific request. When these postural symptoms are present, extreme and prolonged forward bending postures should be avoided.

Conditional regional recurrence risk: The effect of event-free years in different subtypes of breast cancer.

BACKGROUND: Regional recurrence (RR), also known as lymph node recurrence, is an endpoint in several trials concerning reducing axillary treatment in cT1-2N0 breast cancer patients. The risk of RR may decrease with each subsequent event-free year, affecting the yield and consequently usefulness of long (er) follow-up. The aim of this study is to determine the risk of RR as a first event within five years after diagnosis in subtypes of breast cancer, conditional to being event-free for one, two, three and four years. METHODS: From the Netherlands Cancer Registry, cT1-2N0 breast cancer patients diagnosed from 2005 to 2008 were analyzed. Subgroup analysis was performed for pT1-2N+(sn) patients. RR risk was calculated with Kaplan-Meier analysis. Conditional RR (assuming x event-free years) was determined by selecting patients without an event at x years, and calculating the remaining risk for RR within five years after diagnosis. RESULTS: A total of 18,009 cT1-2N0 (all pN stages) breast cancer patients were included. RR occurred in 1.3% of cT1-2N0 and 1.5% of pT1-2N+(sn) patients. The risk of RR varied between subtypes; it was highest for triple negative tumors and lowest for ER + PR + Her2-and ER + Her2+ tumors. After event-free years, the risk of RR decreased subsequently in both groups and in all subtypes. After two event-free years, the risk of RR was 0.8%. CONCLUSION: The absolute yield of follow-up to detect RR beyond two years is low; for every 125 event-free patients, one RR can be expected until five years. This suggests that follow-up longer than two years is of limited value for detecting RR in both clinical and research setting.

Ten-year conditional recurrence risks and overall and relative survival for breast cancer patients in the Netherlands: Taking account of event-free years.

BACKGROUND: Survival estimates from diagnosis are of limited importance for (ex-)breast cancer patients who survived several years, as it includes information on already deceased patients. This study analysed the 10-year conditional risk of recurrent breast cancer in specific prognostic subgroups. Second, we investigated 10-year conditional overall survival (OS) and relative survival (RS), adjusted for confounding. PATIENTS AND METHODS: All women diagnosed in 2005 with operated T1-2N0-1 breast cancer were selected from the Netherlands Cancer Registry. Patients were classified into T1N0, T1N1, T2N0 and T2N1 stage. Ten-year conditional recurrence rates were calculated from diagnosis, and for patients without an event (local [LR], regional recurrence [RR], distant metastasis [DM] or death) every year following diagnosis. Ten-year conditional OS was calculated using multivariable Cox regression. RS was estimated by dividing patient survival rates by those of the general Dutch population. RESULTS: We included 7969 patients: 52.3% had T1N0, 15.3% T1N1, 19.9% T2N0 and 12.5% T2N1 stage. For T1N0, 10-year LR rates changed from 4.6% at diagnosis to 0.5% in year 10. RR rates changed from 2.3% to 0.2%, and DM rates changed from 7.8% to 0.6%. For T2N1 stage, the LR, RR and DM rates changed from 6.2% to 0.8%, 5.2%-0.4% and 19.6%-1.5%, respectively. For the luminal A subtype, LR, RR and DM rates changed from 3.9% to 0.4%, 1.7%-0.5% and 7.3%-1.1%, while for triple negative, these rates changed from 5.6% to 0.7%, 4.9%-0.2% and 16.7%-0%, respectively. Differences between subgroups attenuated over time, and all recurrence rates became ≤1.5% in year 10. Ten-year OS and RS, adjusted for confounding, showed declining risk differences between subgroups over time. CONCLUSION: Differences in recurrence rates, OS and RS between prognostic subgroups declined as years passed by. These results highlight the importance of taking into account disease-free years to more accurately predict (ex-)breast cancer patients' prognosis over time.

The Potential Impact of AMAROS on the Management of the Axilla in Patients with Clinical T1-2N0 Breast Cancer Undergoing Primary Total Mastectomy.

BACKGROUND: Recent trials have demonstrated that axillary observation or axillary radiation therapy (AxRT) is equivalent to axillary node dissection (ALND) for patients with one or two positive sentinel lymph nodes (SLNs). These strategies have been widely adopted for patients having breast conservation. This report demonstrates the potential impact of the AMAROS trial on axillary therapy in a retrospective cohort of mastectomy patients. METHODS: Patients undergoing primary mastectomy for cT1-2N0 breast cancer who had one or two positive SLNs were identified from institutional databases (2005-2015). Locoregional management strategies were evaluated, and variables predictive of the use of postmastectomy radiation therapy (PMRT) were identified. RESULTS: Among 2594 mastectomies, 193 (7%) met the AMAROS eligibility criteria. The median patient age was 50 years (range 22-83 years). Locoregional treatment consisted of ALND + PMRT for 102 patients (53%), ALND alone for 66 patients (34%), PMRT alone for 11 patients (6%), and observation for 14 patients (7%). Overall, 59 ALND patients (35%) had additional positive nodes. In the multivariate analysis, age younger than 50 years (odds ratio [OR] 3.55; 95% confidence interval [CI] 1.57-8.45), lymphovascular invasion (LVI) (OR 5.78; 95% CI 2.53-4.78), macrometastases (OR 3.99; 95% CI 1.54-10.97), and extracapsular extension (OR 11.66; 95% CI 2.55-88.34) were associated with receipt of PMRT. CONCLUSION: In this cohort of AMAROS-eligible patients, 168 (87%) underwent ALND, 102 (61%) of whom also received PMRT, suggesting that AxRT could have been used instead of ALND for a significant number of patients. Preoperative factors associated with the receipt of PMRT, such as young age and LVI, may be useful for defining a multidisciplinary decision-making framework for axillary management in this population.

Clinical tumor stage is the most important predictor of pathological complete response rate after neoadjuvant chemotherapy in breast cancer patients.

BACKGROUND: Pathological complete response (pCR) is the ultimate response in breast cancer patients treated with neoadjuvant chemotherapy (NCT). It might be a surrogate outcome for disease-free survival (DFS) and overall survival (OS). We studied the effect of clinical tumor stage (cT-stage) on tumor pCR and the effect of pCR per cT-stage on 5-year OS and DFS. METHODS: Using the Netherlands Cancer Registry, all primary invasive breast cancer patients treated with NCT from 2005 until 2008 were identified. Univariable logistic regression analysis was performed to evaluate the effect of cT-stage on pCR, stepwise logistic regression analysis to correct for potential confounders and Kaplan-Meier survival analyses to calculate OS and DFS after five years. RESULTS: In 2366 patients, overall pCR rate was 21%. For cT1, cT2, cT3, and cT4, pCR rates were 31, 22, 18, and 17%, respectively. Lower cT-stage (cT1-2 vs cT3-4) was a significant independent predictor of higher pCR rate (p < 0.001, OR 3.15). Furthermore, positive HER2 status (p < 0.001, OR 2.30), negative estrogen receptor status (p = 0.062, OR 1.69), and negative progesterone receptor status (p = 0.008, OR 2.27) were independent predictors of pCR. OS and DFS were up to 20% higher in patients with cT2-4 tumors with pCR versus patients without pCR. DFS was also higher for cT1 tumors with pCR. CONCLUSIONS: The most important predictor of pCR in breast cancer patients is cT-stage: lower cT-stages have significantly higher pCR rates than higher cT-stages. Patients with cT2-4 tumors achieving pCR have higher OS and DFS compared to patients not achieving pCR.

International consensus statement regarding the use of animal models for research on anastomoses in the lower gastrointestinal tract.

PURPOSE: This project aimed to reach consensus on the most appropriate animal models and outcome measures in research on anastomoses in the lower gastrointestinal tract (GIT). The physiology of anastomotic healing remains an important research topic in gastrointestinal surgery. Recent results from experimental studies are limited with regard to comparability and clinical translation. METHODS: PubMed and EMBASE were searched for experimental studies investigating anastomotic healing in the lower GIT published between January 1, 2000 and December 31, 2014 to assess currently used models. All corresponding authors were invited for a Delphi-based analysis that consisted of two online survey rounds followed by a final online recommendation survey to reach consensus on the discussed topics. RESULTS: Two hundred seventy-seven original articles were retrieved and 167 articles were included in the systematic review. Mice, rats, rabbits, pigs, and dogs are currently being used as animal models, with a large variety in surgical techniques and outcome measures. Forty-four corresponding authors participated in the Delphi analysis. In the first two rounds, 39/44 and 35/39 participants completed the survey. In the final meeting, 35 experts reached consensus on 76/122 items in six categories. Mouse, rat, and pig are considered appropriate animal models; rabbit and dog should be abandoned in research regarding bowel anastomoses. ARRIVE guidelines should be followed more strictly. CONCLUSIONS: Consensus was reached on several recommendations for the use of animal models and outcome measurements in research on anastomoses of the lower GIT. Future research should take these suggestions into account to facilitate comparison and clinical translation of results.

Maastricht Delphi consensus on event definitions for classification of recurrence in breast cancer research.

BACKGROUND: In breast cancer studies, many different endpoints are used. Definitions are often not provided or vary between studies. For instance, "local recurrence" may include different components in similar studies. This limits transparency and comparability of results. This project aimed to reach consensus on the definitions of local event, second primary breast cancer, regional and distant event for breast cancer studies. METHODS: The RAND-UCLA Appropriateness method (modified Delphi method) was used. A Consensus Group of international breast cancer experts was formed, including representatives of all involved clinical disciplines. Consensus was reached in two rounds of online questionnaires and one meeting. RESULTS: Twenty-four international breast cancer experts participated. Consensus was reached on 134 items in four categories. Local event is defined as any epithelial breast cancer or ductal carcinoma in situ (DCIS) in the ipsilateral breast, or skin and subcutaneous tissue on the ipsilateral thoracic wall. Second primary breast cancer is defined as epithelial breast cancer in the contralateral breast. Regional events are breast cancer in ipsilateral lymph nodes. A distant event is breast cancer in any other location. Therefore, this includes metastasis in contralateral lymph nodes and breast cancer involving the sternal bone. If feasible, tissue sampling of a first, solitary, lesion suspected for metastasis is highly recommended. CONCLUSION: This project resulted in consensus-based event definitions for classification of recurrence in breast cancer research. Future breast cancer research projects should adopt these definitions to increase transparency. This should facilitate comparison of results and conducting reviews as well as meta-analysis.

A model to predict pathologic complete response of axillary lymph nodes to neoadjuvant chemo(immuno)therapy in patients with clinically node-positive breast cancer.

BACKGROUND: Between 20% and 42% of patients with clinically node-positive breast cancer achieve a pathologic complete response (pCR) of axillary lymph nodes after neoadjuvant chemotherapy or immunotherapy, or both, (chemo[immuno]therapy). Hypothetically, axillary lymph node dissection (ALND) may be safely omitted in these patients. This study aimed to develop a model for predicting axillary pCR in these patients. PATIENTS AND METHODS: We retrospectively identified patients with clinically node-positive breast cancer who were treated with neoadjuvant chemo(immuno)therapy and ALND between 2005 and 2012 in 5 hospitals. Patient and tumor characteristics, neoadjuvant chemo(immuno)therapy regimens, and pathology reports were extracted. Binary logistic regression analysis was used to predict axillary pCR with the following variables: age, tumor stage and type, hormone receptor and human epidermal growth factor receptor 2 (HER2) status, and administration of taxane and trastuzumab. The model was internally validated by bootstrap resampling. The overall performance of the model was assessed by the Brier score and the discriminative performance by receiver operating characteristic (ROC) curve analysis. RESULTS: A model was developed based on 291 patients and was internally validated with a scaled Brier score of 0.14. The area under the ROC curve of this model was 0.77 (95% confidence interval [CI], 0.71-0.82). At a cutoff value of predicted probability ≥ 0.50, the model demonstrated specificity of 88%, sensitivity of 43%, positive predictive value (PPV) of 65%, and negative predictive value (NPV) of 75%. CONCLUSION: This prediction model shows reasonable accuracy for predicting axillary pCR. However, omitting axillary treatment based solely on the nomogram score is not justified. Further research is warranted to noninvasively identify patients with axillary pCR.