Sentinel node biopsy in breast cancer: recommendations for surgeons, pathologists, nuclear physicians and radiologists in Australia and New Zealand

BACKGROUND: Assessment of axillary lymph node status is necessary for patients with invasive breast cancer. Sentinel node biopsy is a new minimally invasive technique that may provide accurate assessment of regional lymph node status while limiting the morbidity associated with axillary clearance. METHODS: A workshop conducted in Adelaide in November 1998 aimed to assess current sentinel node mapping and biopsy techniques, and make recommendations regarding its application in the surgical management of early breast cancer in Australia and New Zealand. RESULTS: At the conclusion of the workshop, a consensus was reached regarding indications, exclusions, sentinel node mapping/biopsy technique, nuclear medicine requirements, pathology and safety of sentinel node biopsy in breast cancer. It was agreed that a feasibility study according to an agreed prospective protocol was necessary to validate the technique by breast surgeons. Surgeons that satisfied validation criteria for the feasibility study could then consider a prospective randomized study comparing sentinel node biopsy with standard axillary dissection. CONCLUSIONS: Sentinel node biopsy in breast cancer involves close cooperation between members of a multidisciplinary team including surgeons, nuclear physicians, pathologists and radiologists. Although the technique has the potential to reduce morbidity associated with axillary surgery, surgical performance in this area will need to be closely monitored to ensure that the technique does not fall into disrepute by adversely affecting breast cancer prognosis.     

Erratum to: Depression,anxiety, and quality of life in a large cohort of patients with rheumatic diseases: common,yet undertreated

Clinical Rheumatology -     

Modified CLSI Extended-Spectrum β-Lactamase (ESBL) Confirmatory Test for Phenotypic Detection of ESBLs among Enterobacteriaceae Producing Various β-Lactamases

The worldwide dissemination of Enterobacteriaceae producing AmpC β-lactamases and carbapenemases makes difficult the phenotypic detection of extended-spectrum β-lactamases (ESBLs), as they may be masked by these additional enzymes. A modification of the CLSI ESBL confirmatory test was developed and evaluated in a comparative study for its ability to successfully detect ESBLs among Enterobacteriaceae producing various carbapenemases (Klebsiella pneumoniae carbapenemase [KPC], VIM, NDM, and OXA-48) and plasmidic or derepressed AmpCs. The modified CLSI ESBL confirmatory test was performed with cefotaxime and ceftazidime disks with and without clavulanate, on which both boronic acid (BA) and EDTA were dispensed. A total of 162 genotypically confirmed ESBL-positive Enterobacteriaceae isolates (83 carbapenemase/ESBL producers, 25 AmpC/ESBL producers, and 54 ESBL-only producers) were examined. For comparison, 139 genotypically confirmed ESBL-negative Enterobacteriaceae isolates (94 of them possessed carbapenemases and 20 possessed AmpCs) were also tested. The standard CLSI ESBL confirmatory test was positive for 106 of the 162 ESBL producers (sensitivity, 65.4%) and showed false-positive results for 4 of the 139 non-ESBL producers (specificity, 97.1%). The modified CLSI ESBL confirmatory test detected 158 of 162 ESBL producers (sensitivity, 97.5%) and showed no false-positive results for non-ESBL producers (specificity, 100%). The findings of the study demonstrate that the modified CLSI ESBL confirmatory test using antibiotic disks containing both BA and EDTA accurately detects ESBLs in Enterobacteriaceae regardless of the coexistence of additional β-lactam resistance mechanisms.     

Air quality–related health damages of food

Agriculture is a major contributor to air pollution, the largest environmental risk factor for mortality in the United States and worldwide. It is largely unknown, however, how individual foods or entire diets affect human health via poor air quality. We show how food production negatively impacts human health by increasing atmospheric fine particulate matter (PM_2.5), and we identify ways to reduce these negative impacts of agriculture. We quantify the air quality–related health damages attributable to 95 agricultural commodities and 67 final food products, which encompass >99% of agricultural production in the United States. Agricultural production in the United States results in 17,900 annual air quality–related deaths, 15,900 of which are from food production. Of those, 80% are attributable to animal-based foods, both directly from animal production and indirectly from growing animal feed. On-farm interventions can reduce PM_2.5-related mortality by 50%, including improved livestock waste management and fertilizer application practices that reduce emissions of ammonia, a secondary PM_2.5 precursor, and improved crop and animal production practices that reduce primary PM_2.5 emissions from tillage, field burning, livestock dust, and machinery. Dietary shifts toward more plant-based foods that maintain protein intake and other nutritional needs could reduce agricultural air quality–related mortality by 68 to 83%. In sum, improved livestock and fertilization practices, and dietary shifts could greatly decrease the health impacts of agriculture caused by its contribution to reduced air quality.

The health and environmental consequences of feeding the increasingly large and affluent global population are becoming increasingly apparent. These consequences have spurred interest in identifying food production practices and diets that improve human health and reduce environmental harm. Recent work has demonstrated that many of the opportunities for food producers and consumers to improve nutritional outcomes also have environmental benefits, such as reducing greenhouse gas emissions, land and water use, and eutrophication (1–6). It is largely unknown, however, how individual foods and diets affect air quality, even though air pollution is the largest environmental mortality risk factor in the United States and globally (7, 8), and agriculture is itself known to be a major contributor to reduced air quality (8, 9). In the United States alone, atmospheric fine particulate matter (PM_2.5) from anthropogenic sources is responsible for about 100,000 premature deaths each year, one-fifth of which are linked to agriculture (10, 11).Here, we show how different foods affect human health by reducing air quality. We consider the emission of pollutants that contribute to atmospheric PM_2.5, the chronic exposure to which increases the incidence of premature mortality from cardiovascular disease, cancer, and stroke (12, 13). These pollutants include directly emitted PM_2.5 (primary PM_2.5) and PM_2.5 formed in the atmosphere (secondary PM_2.5) from the precursors ammonia (NH₃), nitrogen oxides (NO_x), sulfur dioxide (SO₂), and nonmethane volatile organic compounds (NMVOCs). From a spatially explicit inventory of emissions of primary PM_2.5 and secondary PM_2.5 precursors from agricultural supply chain activities for commodities in the contiguous United States (SI Appendix, Figs. S1 and S2) (14, 15) (Materials and Methods), we estimate increases in atmospheric concentrations of total (primary + secondary) PM_2.5 attributable to agricultural emissions; total PM_2.5 transport, chemistry, and removal; and exposure of populations to total PM_2.5 using an ensemble of three independent air quality models (16–19). We describe damages attributable to 95 agricultural commodities and 67 final food products (full list in SI Appendix, Table S1), which cover >99% of US agricultural production (20).     

Rapid dark aging of biomass burning as an overlooked source of oxidized organic aerosol

Oxidized organic aerosol (OOA) is a major component of ambient particulate matter, substantially impacting climate, human health, and ecosystems. OOA is readily produced in the presence of sunlight, and requires days of photooxidation to reach the levels observed in the atmosphere. High concentrations of OOA are thus expected in the summer; however, our current mechanistic understanding fails to explain elevated OOA during wintertime periods of low photochemical activity that coincide with periods of intense biomass burning. As a result, atmospheric models underpredict OOA concentrations by a factor of 3 to 5. Here we show that fresh emissions from biomass burning exposed to NO₂ and O₃ (precursors to the NO₃ radical) rapidly form OOA in the laboratory over a few hours and without any sunlight. The extent of oxidation is sensitive to relative humidity. The resulting OOA chemical composition is consistent with the observed OOA in field studies in major urban areas. Additionally, this dark chemical processing leads to significant enhancements in secondary nitrate aerosol, of which 50 to 60% is estimated to be organic. Simulations that include this understanding of dark chemical processing show that over 70% of organic aerosol from biomass burning is substantially influenced by dark oxidation. This rapid and extensive dark oxidation elevates the importance of nocturnal chemistry and biomass burning as a global source of OOA.

Highly oxidized organic aerosol (OOA) is a dominant component of particulate matter air pollution globally (1–3); however, sources of OOA remain uncertain, limiting the ability of models to accurately represent OOA and thus predict the associated climate, ecosystem, and health implications (4, 5). The current conceptual model of OOA formation suggests that anthropogenic OOA predominantly originates from the oxidation of volatile (VOCs), intermediate volatility (IVOCs), and semivolatile (SVOCs) organic compounds by the OH radical, resulting in lower-volatility products that condense to the particle phase (6). As the OH radical is formed through photolysis and has a very short atmospheric lifetime [less than a second (7)], this oxidation mechanism only occurs in the presence of sunlight. Further, the time scale for OOA formation through oxidation with OH in models is on the order of a few days (8). While this understanding is sufficient in explaining OOA concentrations in summer or periods with high solar radiation, atmospheric models fail to reproduce the observed concentration of OOA in the ambient atmosphere during winter and low-light conditions (9, 10). Fountoukis et al. (9) found simulated OOA concentrations significantly underestimated in wintertime Paris. Tsimpidi et al. (10) also reported an underprediction of simulated OOA globally in winter, suggesting missing sources of both primary OA (POA) and secondary formation pathways. This underproduction suggests a possible overlooked conversion pathway of organic vapors or particles to OOA that is not accounted for in current chemical transport and climate models.As stricter controls on fossil fuel combustion are implemented, residential biomass burning (BB) as a source of heating or cooking is becoming an increasingly important source of OA in urban environments (1, 11, 12). Further, increasing rates of wildfires from climate change are increasing the frequency of smoke-impacted days in urban areas (12–14). BB emissions include high concentrations of POA, SVOCs, IVOCs, and VOCs (15, 16), thus making BB a key source of OOA. Previous research has focused on quantifying the concentration of OOA formed through photochemical oxidation reactions (i.e., OH) with BB emissions (17, 18). However, oxidation of BB emissions in low or no sunlight is less well understood and is not included in chemical transport models. As opposed to OH, the NO₃ radical is formed through reactions with NO₂ and O₃ and is rapidly lost in the presence of sunlight (19). Thus, the NO₃ radical is only available in significant concentrations at night or other low-light conditions (20, 21). Previous research has established that biogenic VOCs may undergo oxidation at night when mixed with anthropogenic emissions containing NO₂ and O₃ (19, 22–27). There have been only a few studies that consider that nighttime oxidation of residential wood combustion may proceed through similar pathways (28–31); however, the magnitude and relevance to observed OOA in the ambient atmosphere has not yet been established. By combining laboratory experiments and ambient observations to inform a chemical transport model, we present strong evidence that nighttime oxidation of BB plumes (proceeding through reactions with O₃ and the NO₃ radical) is an important source of OOA.     

Laparoscopic versus open appendectomy： Which way to go？

AIM： To compare the outcome of laparoscopic versus open appendectomy. METHODS： Prospectively collected data from 293 consecutive patients with acute appendicitis were studied. These comprised of 165 patients who underwent conventional appendectomy and 128 patients treated laparoscopically. The two groups were compared with respect to operative time, length of hospital stay, postoperative pain, complication rate and cost. RESULTS： There were no statistical differences regarding patient characteristics between the two groups. Conversion to laparotomy was necessary in 2 patients （1.5%）. Laparoscopic appendectomy was associated with a shorter hospital stay （2.2 d vs 3.1 d, P = 0.04）, and lower incidence of wound infection （5.3% vs 12.8%, P = 0.03）. However, in patients with complicated disease, intra-abdominal abscess formation was more common after laparoscopic appendectomy （5.3% vs 2.1%, P = 0.002）. The operative time and analgesia requirements were similar in the two groups. The cost of treatment was higher by 370 in the laparoscopic group. CONCLUSION： Laparoscopic appendectomy is as safe and efficient as open appendectomy, provided surgical experience and equipment are available.     

Role of tumour necrosis factor alpha in experimental arthritis: separate activity of interleukin 1beta in chronicity and cartilage destruction

Chronic arthritis is characterised by persistent joint inflammation and concomitant joint destruction. Using murine arthritis models and neutralising antibodies as well as cytokine specific knockout conditions, it was found that tumour necrosis factor alpha (TNFalpha) is important in early joint swelling. Membrane bound TNFalpha is sufficient to drive this aspect of inflammation as well as the acute cellular infiltrate in the synovial tissue. Interleukin 1 (IL1) is not necessarily a dominant cytokine in early joint swelling, but has a pivotal role in sustained cellular infiltration and erosive cartilage damage. TNFalpha independent IL1 production is a prominent feature in murine arthritis models. These observations provide evidence for potential uncoupling of joint inflammation and erosive changes, implying that both cytokines need to be targeted to achieve optimal treatment.     

CASE REPORT: Light Chain Deposition Disease of the Liver Without Renal Involvement in a Patient with Multiple Myeloma Related to Liver Failure and Rapid Fatal Outcome

We describe a 36-year-old man with advanced multiple myeloma (Salmon and Durie stage III) who developed jaundice and severe cholestasis after a first cure with systemic chemotherapy of vincristine, doxorubicin, and oral dexamethasone (VAD). Serology for hepatitis A, B, and C and for CMV was negative. A liver ultrasound and CT scan showed mild hepatomegaly without evidence of extrahepatic or intrahepatic biliary tree dilatation. A percutaneous liver biopsy revealed perisinusoidal deposits of an abundant slightly eosinophilic, PAS-positive amorphous substance. Immunohistochemistry showed positivity for kappa-light chains and was negative for lambda-light chains, for IgA, IgG, IgM, and IgD immunoglobulins as well as for AA and AL proteins and for amyloid P component. A diagnosis of light chain deposition disease (LCDD) of the liver was made. The patient developed rapid deterioration of liver function, leading to a multisystem dysfunction and death. The occurrence of LCDD in multiple myeloma is close to 5% and myeloma is the underlying disease in two thirds of patients with LCDD. The kidneys are involved in almost all cases of LCDD and renal dysfunction usually reveals the disease. Only three patients with LCDD of the liver without overt renal involvement have been reported so far. This is the first observation of LCDD presenting with jaundice and severe cholestasis shortly after the diagnosis of high tumor mass myeloma, without overt renal involvement, leading rapidly to the patient's death.