A systematic review of axillary nodal irradiation for the management of the axilla in patients with early-stage breast cancer.

BACKGROUND: Given numerous publications and clinical trials regarding axillary management in breast cancer, we sought to summarize this complex literature to help clarify this field for clinicians. This systematic review focuses on the role of irradiation of the axillary nodes (locoregional nodal irradiation [LRNI]) in the management of the axilla in patients with early-stage breast cancer in various clinical settings. METHODS: We searched MEDLINE and EMBASE databases, the Cochrane library, the proceedings of the ASCO, the ASTRO, the ESMO, the ESTRO, and the San Antonio Breast Cancer Symposium (2016-2019) meetings. The quality of the studies was assessed with design-specific tools. The study was registered in PROSPERO. RESULTS: We included one systematic review, one individual patient data (IPD) meta-analysis, and five randomized controlled trials (RCTs). After axillary lymph node dissection (ALND), LRNI resulted in small benefits in breast cancer specific mortality, locoregional recurrence, and distant metastases-free survival but not overall survival. After a positive sentinel node biopsy (SLNB), LRNI may provide equivalent locoregional control and disease-free survival (DFS) compared to ALND with a lower risk of lymphedema. No randomized data is available for the neoadjuvant setting. CONCLUSIONS: The summary of the role of radiation, is relevant to radiation oncologists for choosing the correct cohort of patient requiring LRNI and to surgeons making clinical decisions regarding the timing and type of breast reconstruction offered to patients.

Quality of recovery scores in deep serratus anterior plane block vs. sham block in ambulatory breast cancer surgery: a randomised controlled trial.

Deep serratus anterior plane block has been widely adopted as an analgesic adjunct for patients undergoing breast surgery, but robust supporting evidence of efficacy is lacking. We randomly allocated 40 patients undergoing simple or partial mastectomy with sentinel node biopsy to receive either a pre-operative deep serratus anterior plane block (serratus group) or a placebo injection (sham group), in addition to systemic analgesia. The primary outcome measure was the quality of recovery score at discharge, as assessed by the quality of recovery-15 questionnaire at various time-points. Secondary analgesic outcomes included: pain severity; postoperative opioid consumption; opioid-related side-effects; patient satisfaction up to 7 days postoperatively; and persistent postoperative pain up to 3 months after surgery. All patients who were recruited completed the study. There were no differences in the quality of recovery-15 scores between patients in the serratus and control groups, with mean (SD) scores of 96 (14) and 102 (20) for the control and serratus groups, respectively. We were also unable to detect differences in any of the secondary analgesic outcomes examined. The addition of a deep serratus anterior plane block to systemic analgesia does not enhance quality of recovery in patients undergoing ambulatory breast cancer surgery.

Robot-assisted nipple-sparing mastectomy: systematic review.

BACKGROUND: The growing volume of studies of robot-assisted nipple-sparing mastectomy requires critical assessment. This review synthesizes the data on safety, feasibility, oncological and cosmetic outcomes, and patient-reported outcome measures (PROMs) for robot-assisted nipple-sparing mastectomy. METHODS: A systematic review was performed using MEDLINE, MEDLINE In-Process/ePubs, Embase/Embase Classic, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, LILACS, PubMed, ClinicalTrials.Gov, WHO ICTRP and the grey literature. Original studies reporting on patients with breast cancer or at increased risk of breast cancer undergoing robot-assisted nipple-sparing mastectomy were included. Risk of bias was assessed using the Institute of Health Economics Case Series Quality Appraisal Checklist. RESULTS: Of 7177 titles screened, eight articles were included, reporting on 249 robot-assisted nipple-sparing mastectomies in 187 women. The indication was either therapeutic (58·6 per cent) or prophylactic (41·4 per cent), with immediate reconstruction performed in 96·8 per cent. Surgical techniques followed a similar approach, with variations in incision, robot models, camera and insufflation. Postoperative morbidity included skin complications, lymphocele, infection, seroma, haematoma and skin ischaemia/necrosis. Complications specific to the nipple-areolar complex included ischaemia and necrosis. There were two conversions owing to haemorrhage, but no intraoperative deaths. Three patients had positive margins. Follow-up time ranged from 3·4 to 44·8 months. Locoregional recurrences were not observed. PROMs and objective cosmetic outcomes were reported inconsistently. Data on nipple sensitivity were not reported. CONCLUSION: Robot-assisted nipple-sparing mastectomy is feasible with acceptable short-term outcomes but it remains in the assessment phase.

ANTECEDENTES: El volumen creciente de estudios en los que se realiza una mastectomía con preservación de pezón asistida por robot requiere una evaluación crítica. Esta revisión sintetiza la seguridad, factibilidad y los resultados oncológicos, estéticos y percibidos por la paciente (patient-reported outcome measures, PROMs) tras la mastectomía con preservación del pezón asistida por robot. MÉTODOS: Se realizó una revisión sistemática utilizando Medline, Medline In-Process/ePubs, Embase/Embase Classic, el registro Cochrane Central de ensayos clínicos, la base de datos Cochrane de revisiones sistemáticas, LILACS, PubMed, ClinicalTrials.Gov, WHO ICTRP y la literatura gris (desde su inicio hasta el 3/5/2020). Se incluyeron los estudios originales en los que se realizaba una mastectomía con preservación de pezón asistida por robot en pacientes con cáncer de mama o con un aumento del riesgo de cáncer de mama. La posibilidad de sesgo se evaluó mediante la lista de verificación para la evaluación de la calidad de series de casos del Instituto de Economía de la Salud (Institute of Health Economics). RESULTADOS: De 7.177 artículos identificados, se seleccionaron 8 con 249 mastectomías con preservación de pezón asistidas por robot en 187 mujeres. La indicación fue terapéutica (58,6%) o profiláctica (41,4%) y la reconstrucción se realizó de forma inmediata en el 96,8% de los casos. La mediana de seguimiento más larga fue de 19 meses (rango 1,3-44 meses), y no se detectaron recidivas locorregionales. La técnica quirúrgica siguió un esquema similar, con diferencias en la incisión, modelo de robot, cámara e insuflación. Las complicaciones incluyeron complicaciones cutáneas, como necrosis, linfocele, infección de heridas, hematoma, seroma y necrosis del pezón. Hubo dos conversiones por hemorragia, pero ningún caso de mortalidad intraoperatoria. La presentación de datos respecto a los PROMs y los resultados cosméticos fue irregular. CONCLUSIÓN: La mastectomía con preservación de pezón asistida por robot es segura, factible y tiene resultados oncológicos aceptables a corto plazo. El procedimiento sigue siendo experimental y es preciso evaluar los resultados oncológicos a largo plazo y los PROMs en ensayos prospectivos comparativos y aleatorizados.

Pertuzumab, trastuzumab and taxane-based treatment for visceral organ metastatic, trastuzumab-naïve breast cancer: real-life practice outcomes.

PURPOSE: In this study, we aimed to describe the real-life practice outcomes of pertuzumab-trastuzumab-taxane (PTT) combination in visceral organ metastatic, trastuzumab-naive breast cancer (BC) patients. METHODS: This study was conducted by Turkish Oncology Group and included 317 patients' data from 36 centers. RESULTS: Median age was 51 (22-82). Median PFS was 28.5 months, while median OS was 40.3 months. Patients with brain metastases (n: 13, 4.1%) had worse PFS (16.8 m vs. 28.5 m; p = 0.002) and OS (26.7 m vs. 40.3 m; p = 0.009). Patients older than 65 years of age (n: 42, 13.2%) had significantly lower OS results (19.8 m vs. 40.3 m; p = 0.01). Two hundred sixty-eight patients (86.7%) received docetaxel while 37 patients (11.7%) received paclitaxel. PFS and OS were similar between taxane groups. In eight patients (2.5%), 5-40% ejection fraction decrement from baseline was detected without any clinical sign of heart failure. CONCLUSIONS: Our RLP trial included only visceral metastatic, trastuzumab-naïve BC patients including cases with brain involvement who received PTT combination in the first-line treatment. Regardless of negative prognostic characteristics, our results are in parallel with pivotal trial. Further strategies for brain metastasis should be developed to improve outcomes despite encouraging results with PTT treatment. Taxane selection can be personalized and endocrine maintenance may further improve outcomes after taxanes were discontinued. To our knowledge, this is the largest scale real-life clinical practice study of pertuzumab-trastuzumab-taxane therapy to date.

PATI: Patient accessed tailored information: A pilot study to evaluate the effect on preoperative breast cancer patients of information delivered via a mobile application.

OBJECTIVES: The information needs of cancer patients are highly variable. Literature suggests an improved ability to modulate personalised stress, increased patient involvement with decision making, greater satisfaction with treatment choices and reduced anxiety levels in cancer patients who have access to information. The aim of this project was to evaluate the effects of a mobile information application on anxiety levels of patients undergoing surgery for breast cancer. MATERIALS AND METHODS: An application was developed for use with Apple iPad containing information on basic breast cancer biology, different treatments used and surgical techniques. Content and face validity studies were performed. A randomized control trial was designed, with a 1:2 allocation. Data collected include basic demographics and type of surgery. Questionnaires used included: the HADS, Mini-MAC, information technology familiarity and information satisfaction. RESULTS: A total of 39 women participated. 13 women had access to an iPad containing additional information and 26 women acted as controls. The mean age was 54 and technology familiarity was similar among both groups. Anxiety and depression scores at seven days were significantly lower in control patients without access to the additional information provided by the mobile application (p = 0.022 and 0.029 respectively). CONCLUSION: Anxiety and depression in breast cancer patients is both multifactorial and significant, with anxiety levels directly correlating with reduced quality of life. Intuitively, information should improve anxiety levels, however, we have demonstrated that surgical patients with less information reported significantly lower anxiety. We advise the thorough testing and auditing of information initiatives before deployment.

An International Multicenter Review of the Malignancy Rate of Excised Papillomatous Breast Lesions.

BACKGROUND: Papillary lesions of the breast are a relatively rare, but heterogeneous group ranging from benign to atypical and malignant. Debate exists regarding the optimal management of these lesions. In the absence of more accurate risk-stratification models, traditional management guidelines recommend surgical excision, despite the majority of lesions proving benign. This study sought to determine the rate of malignancy in excised breast papillomas and to elucidate whether there exists a population in which surgical excision may be unnecessary. METHODS: A multicenter international retrospective review of core biopsy diagnosed breast papillomas and papillary lesions was performed between 2009 and 2013, following institutional ethical approval. Patient demographics, histopathological, and radiological findings were recorded. All data was tabulated, and statistical analysis performed using Stata. RESULTS: A total of 238 patients were included in the final analysis. The age profile of those with benign pathology was significantly younger than those with malignant pathology (p < 0.001). Atypia on core needle biopsy was significantly associated with a final pathological diagnosis of malignancy (OR = 2.73). The upgrade rate from benign core needle biopsy to malignancy on the final pathological sample was 14.4 %; however, only 3.7 % had invasive cancer. CONCLUSIONS: This international dataset is one of the largest in the published literature relating to breast papillomas. The overall risk of malignancy is significantly associated with older age and the presence of atypia on core needle biopsy. It may be possible to stratify higher-risk patients according to age and core needle biopsy findings, thereby avoiding surgery on low-risk patients.

Contribution of low-molecular weight heparin addition to concomitant chemoradiotherapy in the treatment of glioblastoma multiforme.

PURPOSE: Glioblastoma multiforme (GBM) is the most common brain tumor in adults and has a very aggressive course. Median survival is as short as 2 years with standard treatment (chemoradiotherapy followed by adjuvant temozolomide). The purpose of this study was to determine the contribution of low molecular weight heparin (LMWH) addition to concomitant chemoradiotherapy in the treatment of GBM. METHODS: All patients with newly diagnosed GBM between March 2004-May 2009 were evaluated. After surgical intervention (total, subtotal resection or only biopsy) all of them were treated with concomitant chemoradiotherapy (2 Gy daily, 5 days a week, 30 fractions, total tumor dose 60 Gy; and 75 mg/m² temozolomide, 7 days a week), followed by adjuvant temozolomide (6 cycles, 150-200 mg/m², 5 days every 28 days), with or without LMWH (4000 IU/day, 7 days a week, concomitant with radiotherapy) because of risk of thrombosis. The primary endpoint was the determination of progression-free survival (PFS) and overall survival (OS); secondary endpoints were 1- and 2-year OS survival. RESULTS: 30 patients (13 patients in the group non receiving LMWH (LMWH-) and 17 patients in the group receiving LMWH (LMWH+)) were included in the study. Median age was 54 years (range 24-75). Median PFS was 57 and 38 weeks in LMWH+ and LMWH- groups, respectively (p=0.068). Median OS was 69 and 44 weeks (p=0.095), 1-year OS survival 84.6 and 41.2% (p=0.016), and 2-year OS survival 38.5 and 5.9% in LMWH+ and LMWH-, respectively (p=0.061). No significant difference was noted between the two groups for grade 3-4 toxicity (p>0.05). CONCLUSION: Better PFS, OS and 2-year OS survival were obtained in present study with the addition of LMWH to concomitant chemoradiation for GBM but without statistical significance. One-year OS survival was statistically significant favoring the LMWH group. The addition of LMWH did not increase temozolomide toxicity.

How to increase the diagnostic value of malignancy-related ascites: discriminative ability of the ascitic tumour markers.

Making a differential diagnosis between malignant and non-malignant ascites is an important clinical issue, but cytological examination has a relatively low diagnostic sensitivity. This study aimed to find a discriminative model that distinguished between malignancy-related and non-malignant ascites. The study included 107 patients: 50 with non-malignant and 57 with malignant ascites. Ascites was analysed using a range of tumour markers and standard cytology. Standardized canonical discriminant function coefficients were used to distinguish between ascites types. The combination of carbohydrate antigen (CA) 15-3, carcinoembryonic antigen (CEA) and cytokeratin 19 fragments (CYFRA-21.1) discriminated between malignancy-related ascites and non-malignant ascites with an accuracy of 98.8% compared with an accuracy of 77.8% for cytological examination. In conclusion, the use of a discriminant function constructed from a combination of CA15-3, CEA and CYFRA-21.1 could distinguish malignant from non-malignant ascites with greater accuracy than cytological examination. Further studies in larger population groups are warranted.

Factors affecting axillary lymph node retrieval and assessment in breast cancer patients.

BACKGROUND: Breast cancer is the most common female cancer in North America. Axillary lymph node dissection (ALND) is important for staging, prognosis, and adjuvant treatment decisions. The purpose of this study was to identify factors that affect the number of lymph nodes (LN) retrieved in ALND for breast cancer. METHODS: All patients who underwent ALND for breast cancer at Sunnybrook Health Sciences Centre and Women's College Hospital between July 1999 and June 2006 were included. The number of LN retrieved was identified from pathology reports. Univariate and multivariate analysis was undertaken to identify variables influencing this outcome. RESULTS: 1084 patients were identified with a mean number of LN of 14.5. In multivariate analyses, significant covariates included sentinel LN biopsy (P = 0.011), degree of extranodal extension (P = 0.005), tumor grade (P = 0.058), and age (P = 0.043). Thirteen percent of the variation in LN yield was accounted for by institutional, provider, patient, and tumor related factors, leaving 87% attributable to inherent biological or other differences between patients. CONCLUSION: The yield of ALND may be influenced by multiple factors, often not related to the surgery. In settings where >10 LNs are routinely retrieved at ALND, biological variation between patients should be recognized as major a contributor to the LN yield. Adjuvant treatment decisions based on this outcome should take this into consideration.

Clinical significance of elevated antinuclear antibody test in patients with Hodgkin's and Non-Hodgkin's lymphoma: a single center experience.

AIM: There is an increased risk of lymphoma subsequent to autoimmune conditions. Autoimmune disorders may occur in the course of lymphomas. In this study, the association of autoimmunity and related autoantibodies within non-Hodgkin's (NHL) and Hodgkin's lymphoma (HL) patients has been investigated. METHODS: The study enrolled 119 patients affected by NHL and 60 patients affected by HL for the presence of autoantibodies and autoimmune diseases. Afterwards, the results between the two lymphoma groups have been confronted. RESULTS: Autoimmune diseases were diagnosed in eight (6.7%) patients with NHL and three patients with HL (5%) (P=0.651). Thirty-four (28.5%) patients with NHL and 14 (23.3%) patients with HL displayed autoantibody positivity (P=0.083). As regards HL cases, antinuclear antibodies (ANA) were detected in 12 (20%) and anti PM-Scl in two patients (3.3%). None the patients had anti Jo-1, anti Scl-70, anti Sm, anti nRNP/Sm, anti single-stranded DNA (anti-ssDNA), anti double-stranded DNA (anti-dsDNA), antihistones, antinucleosomes, anti SS-A, anti SS-B or anti CENP-B autoantibodies. In patients affected by NHL ANA was detected in 16 (13.4%), anti SS-A and anti SS-B in two (1.7%), anti CENP-B in eight (6.7%) and anti PM-Scl in eight patients (6.7%). None of the patients had anti Jo-1, anti Scl-70, anti Sm, anti nRNP/Sm, anti ssDNA, antihistones or antinucleosome antibodies. There was a statistically significant difference between patients with HL and NHL in terms of anti CENP-B positivity (P=0.040). CONCLUSION: In conclusion, ANA and related autoantibodies can frequently be detected during lymphoma treatment. However, the majority of lymphoma patients with positive ANA did not display autoimmune diseases, demonstrating the lack of a strict correlation between the presence of ANA and autoimmune diseases.

Parathyroid hormone as a marker for the differential diagnosis of acute and chronic renal failure.

It is often difficult to distinguish acute renal failure clinically from chronic renal failure, especially in patients who do not have records of their medical history. We investigated the magnitude of iPTH increase in ARF and the potential role of iPTH as a marker for differential diagnosis of ARF and CRF in new patients referred to our renal unit. We prospectively analyzed 122 (ARF n = 64, CRF n = 58) patients referred to our renal unit with serum creatinine higher than 2 mg/dL. ROC curve analysis was performed to investigate role of iPTH for differentiating ARF from CRF. The sensitivity, specificity, and positive predictive value of iPTH in discrimination of ARF and CRF were calculated. There was no statistically significant difference regarding the means of age, sex distribution, and serum chemistry between patients with ARF or CRF. But serum iPTH (p < 0.0001) levels were lower in patients with ARF than in those with CRF. A cutoff, set at 170 pg/mL for iPTH to discriminate patients with CRF, yielded a sensitivity of 88% and a specificity of 89%. This study confirms that the iPTH measurement is of clinical value in differentiating acute from chronic renal failure.

A simple way to estimate mean plasma glucose and to identify Type 2 diabetic subjects with poor glycaemic control when a standardized HbA1c assay is not available.

AIMS: To evaluate the relationship between HbA(1c) and fasting plasma glucose (FPG) and postprandial plasma glucose (PPG) levels, and to estimate the mean plasma glucose (mPG) derived from FPG and PPG that would predict Type 2 diabetic subjects with poor glycaemic control. METHODS: FPG, PPG and HbA(1c) values from 565 Type 2 diabetic patients (247 men and 318 women) were recorded. Linear regression analysis and Pearson's correlation was used to determine the relationship between HbA(1c), FPG and PPG. FPG and PPG were included as explanatory variables of HbA(1c) in linear regression analysis. RESULTS: The American Diabetes Association's objective of achieving an HbA(1c) level < 7.0% was obtained in 26.2% of the patients. The coefficients of FPG and PPG which determined HbA(1c) were similar. Therefore, mPG was calculated using the equation (FPG + PPG)/2. Pearson's correlation coefficient for HbA(1c) and FPG, PPG and mPG were 0.723 (P < 0.0001), 0.734 and 0.761 (P < 0.0001), respectively. A mPG cut-off value of 10 mmol/l predicted an HbA(1c) > 7% in the whole population, with a sensitivity of 84.2% and specificity of 80.4%. The area was high (0.90) in receiver-operating characteristic (ROC) curve analysis performed to examine the performance of mPG to predict HbA(1c) > 7%. CONCLUSIONS: The mPG derived from FPG and PPG correlates strongly with HbA(1c). We therefore suggest that using a cut-off of 10 mmol/l for mPG may be appropriate in diabetes management in the primary-care setting, where most management of Type 2 diabetes occurs.

A tale of two syndromes: ovarian hyperstimulation and abdominal compartment.

Abdominal compartment syndrome complicated severe ovarian hyperstimulation in a 35 year old woman with multiple bowel resections due to Crohn's disease. Pain from ovarian enlargement necessitated hospital admission. Despite intravenous fluid administration and heparin prophylaxis, ilio-femoral deep vein thrombosis developed. Treatment by intravenous heparin was complicated by repeated intra-ovarian bleeding, anaemia and acute renal failure requiring haemodialysis. Intra-abdominal pressures were elevated. After placement of an inferior vena caval filter and discontinuation of heparin, there was slow spontaneous recovery without surgery.