Novel Application of Hydrodissection in Laparoscopic Cholecystectomy for Gangrenous Gallbladders.

INTRODUCTION: Laparoscopic cholecystectomy (LC) for gangrenous gallbladders (GGBs) can be challenging and represent a significant number of LC cases, necessitating more efficacious surgical techniques. Currently, the standard treatment for GGBs is blunt dissection which can have high iatrogenic complication rates. To our knowledge, this is the first large retrospective study conducted on the novel application of hydrodissection (HD) in LCs for GGBs. METHODS: In this retrospective study of 386 LCs, data were collected for patient demographics, medical comorbidities, operating time (OT), anesthesia time (AT), length of stay (LOS), estimated blood loss, conversion to open procedures, 30-day readmissions, and mortality. Patients were categorized into four groups: (1) Vyas employing HD for GGBs (VHG), (2) non-Vyas group of five surgeons not employing HD for GGBs (NVG), (3) Vyas treating non-GGBs, and (4) non-Vyas group of five surgeons treating non-GGBs. Control groups were age-matched and sex-matched. Statistical analysis used descriptive statistics, Mann-Whitney U testing, and chi-squared testing (α = 0.05). RESULTS: This study demonstrated significantly decreased (P < 0.05) OT (P = 0.001), AT (P < 0.001), LOS (P = 0.015), and conversion to open procedures (P = 0.047) between the VHG and NVG groups, with HD reducing OT by 35.5% compared to blunt dissection. This study did not demonstrate significantly decreased (P > 0.05) estimated blood loss (P = 0.185) and 30-day readmissions (P = 0.531) between the VHG and NVG groups, but they were trending toward significant. There were no mortalities in this study. CONCLUSIONS: HD is associated with improved surgical outcomes of LCs for GGBs demonstrated by reduced OT, AT, LOS, and conversion to open procedures. Further multi-institutional studies are needed to validate HD implementation and further dissemination.

Climate change risk to pheromone application in pest management.

Since of the first sex pheromone and the adoption of pheromone in pest management, the global pheromone market size has grown to reach USD 2.4 billion per year in 2019. This has enabled the development of environmentally friendly approaches that significantly reduce the application of pesticides. Recently, there have been reports of the failure of various commercial codlemone: (E,E)-8,10-dodecadien-1-ol formulations used for monitoring the apple pest codling moth, Cydia pomonella (L.). This work was initiated to investigate factors behind the lack of efficacy of codlemone lure in the Northern Hemisphere (Germany) and Southern Hemisphere (New Zealand). We hypothesised that the observed failure could be due to two main factors: (a) a shift in the response of male codling moth to codlemone and (b) degradation of codlemone under field conditions that renders the lure less attractive. Field trial tests of various doses and blends containing minor pheromone compounds suggested no change in response of male codling moth. The addition of an antioxidant and a UV stabiliser to codlemone resulted in a significant increase in the number of males caught in Germany, but not in New Zealand. Mean maximum temperatures during the growing season since 2004 indicate a 3 °C increase to 35 °C in Germany, but just a 1.5 °C rise to 30 °C in New Zealand. Chemical analysis of the lures used in the field trials in Germany and New Zealand indicated more degradation products and reduced half-life of the lures in Germany compared with those in New Zealand. Heating codlemone lures to 32 °C significantly reduced the number of males caught in traps and increased the isomeric and chemical impurities of codlemone compared with unheated lures. Our data provide the first evidence that climate change affects pheromone molecule stability, thus reducing its biological efficacy. Our finding suggests that climate change could be a general problem for chemical communication and, therefore, could affect the integrity of natural ecosystems.

Transparent antifouling material for improved operative field visibility in endoscopy.

Camera-guided instruments, such as endoscopes, have become an essential component of contemporary medicine. The 15-20 million endoscopies performed every year in the United States alone demonstrate the tremendous impact of this technology. However, doctors heavily rely on the visual feedback provided by the endoscope camera, which is routinely compromised when body fluids and fogging occlude the lens, requiring lengthy cleaning procedures that include irrigation, tissue rubbing, suction, and even temporary removal of the endoscope for external cleaning. Bronchoscopies are especially affected because they are performed on delicate tissue, in high-humidity environments with exposure to extremely adhesive biological fluids such as mucus and blood. Here, we present a repellent, liquid-infused coating on an endoscope lens capable of preventing vision loss after repeated submersions in blood and mucus. The material properties of the coating, including conformability, mechanical adhesion, transparency, oil type, and biocompatibility, were optimized in comprehensive in vitro and ex vivo studies. Extensive bronchoscopy procedures performed in vivo on porcine lungs showed significantly reduced fouling, resulting in either unnecessary or ∼10-15 times shorter and less intensive lens clearing procedures compared with an untreated endoscope. We believe that the material developed in this study opens up opportunities in the design of next-generation endoscopes that will improve visual field, display unprecedented antibacterial and antifouling properties, reduce the duration of the procedure, and enable visualization of currently unreachable parts of the body, thus offering enormous potential for disease diagnosis and treatment.

Assigning clinical meaning to somatic and germ-line whole-exome sequencing data in a prospective cancer precision medicine study.

PURPOSE: Implementing cancer precision medicine in the clinic requires assessing the therapeutic relevance of genomic alterations. A main challenge is the systematic interpretation of whole-exome sequencing (WES) data for clinical care. METHODS: One hundred sixty-five adults with metastatic colorectal and lung adenocarcinomas were prospectively enrolled in the CanSeq study. WES was performed on DNA extracted from formalin-fixed paraffin-embedded tumor biopsy samples and matched blood samples. Somatic and germ-line alterations were ranked according to therapeutic or clinical relevance. Results were interpreted using an integrated somatic and germ-line framework and returned in accordance with patient preferences. RESULTS: At the time of this analysis, WES had been performed and results returned to the clinical team for 165 participants. Of 768 curated somatic alterations, only 31% were associated with clinical evidence and 69% with preclinical or inferential evidence. Of 806 curated germ-line variants, 5% were clinically relevant and 56% were classified as variants of unknown significance. The variant review and decision-making processes were effective when the process was changed from that of a Molecular Tumor Board to a protocol-based approach. CONCLUSION: The development of novel interpretive and decision-support tools that draw from scientific and clinical evidence will be crucial for the success of cancer precision medicine in WES studies.Genet Med advance online publication 26 January 2017.

Delay of treatment change after objective progression on first-line erlotinib in epidermal growth factor receptor-mutant lung cancer.

BACKGROUND: Erlotinib is a highly active epidermal growth factor receptor (EGFR) kinase inhibitor that is approved for first-line use in lung cancers harboring EGFR mutations. Anecdotal experience suggests that this drug may provide continued disease control after patients develop objective progression of disease (PD), although this has not been systematically studied to date. METHODS: Patients who had Response Evaluation Criteria In Solid Tumors-defined PD who were participating in 3 prospective trials of first-line erlotinib in advanced lung cancer were studied retrospectively, and the progression characteristics were compared between patients with and without EGFR-sensitizing mutations. Factors were studied that influenced the time until treatment change (TTC), defined as the time from PD to the start of a new systemic therapy or death. The rate of tumor progression was assessed by comparing tumor measurements between the computed tomography scan obtained at the time of PD and the preceding scan. RESULTS: In total, 92 eligible patients were studied, including 42 with and 50 without an EGFR-sensitizing mutation. The EGFR-mutant cohort had a slower rate of progression (P = .003) and a longer TTC (P < .001). Among the patients with EGFR-mutant cancers, 28 (66%) continued single-agent erlotinib after PD, and 21 (50%) were able to delay a change in systemic therapy for >3 months; only 2 patients received local debulking therapy during that period. Multivariate analysis of the patients with EGFR-mutant tumors demonstrated that a longer time to progression, a slower rate of progression, and a lack of new extrathoracic metastases were associated with a longer TTC. CONCLUSIONS: A change in systemic therapy commonly can be delayed in patients with EGFR-mutant lung cancer who objectively progress on first-line erlotinib, particularly in those with a longer time to progression, a slow rate of progression, and a lack of new extrathoracic metastases.

Non-invasive assessment of liver fibrosis with transient elastography (FibroScan®): applying the cut-offs of M probe to XL probe.

UNLABELLED: BACKGROUND AND RATIONALE FOR THE STUDY: Limited studies have aimed to define the cut-offs of XL probe (XL cut-offs) for different stages of liver fibrosis, whereas those of M probe (M cut-offs) may not be applicable to XL probe. We aimed to derive appropriate XL cut-offs in overweight patients. Patients with liver stiffness measurement (LSM) by both probes were recruited. XL cut-offs probe for corresponding M cut-offs were derived from an exploratory cohort, and subsequently validated in a subgroup patients also underwent liver biopsy. The diagnostic accuracy of XL cut-offs to diagnose advanced fibrosis was evaluated. RESULTS: Total 517 patients (63% male, mean age 58) who had reliable LSM by both probes were included in the exploratory cohort. There was a strong correlation between the LSM by M probe (LSM-M) and LSM by XL probe (LSM-XL) (r² = 0.89, p < 0.001). A decision tree using LSM-XL was learnt to predict the 3 categories of LSM-M (< 6.0kPa, 6.0-11.9kPa and ≥ 12.0kPa), and XL cut-offs at 4.8kPa and 10.7kPa were identified. These cut-offs were subsequently validated in a cohort of 147 patients who underwent liver biopsy. The overall accuracy was 89% among 62 patients whose LSM-XL < 4.8kPa or ≥ 10.7kPa. These cut-offs would have avoided under-staging of fibrosis among patients with body mass index (BMI) > 25-30 kg/m2 but not > 30 kg/m2. CONCLUSIONS: XL cut-offs at 4.8kPa and 10.7kPa were the best estimates of 6.0kPa and 12.0kPa of M probe for patients with BMI > 25-30 kg/m2. Patients with BMI > 30 kg/m² might use M probe cut-offs for XL probe.

Colorectal Cancer Screening Challenges in the Recent Afghan Refugee Population: A Comprehensive Review Article.

Colorectal cancer (CRC) is more prevalent in south-central Asian countries, particularly the Afghan population. Screening for CRC in the Afghan population has always been challenging, primarily due to the tribal and social cultures, lack of facilities, and lack of education. The United States (US) will soon face a significantly massive influx of Afghan refugees. It becomes imperative to initiate and implement effective measures regarding CRC screening in these refugee populations. The current review article aims to identify the most likely challenges faced for CRC screening in this Afghan refugee population in the US and address the possible measures to overcome these challenges.

Comparing Deliveries of Sterile Codling Moth (Lepidoptera: Tortricidae) by Two Types of Unmanned Aerial Systems and from the Ground.

New Zealand apple exports must meet strict phytosanitary measures to eliminate codling moth (Cydia pomonella Linnaeus) (Lepidoptera: Tortricidae) larval infestation. This study was part of a program attempting the localized eradication of codling moth within an isolated cluster of seven orchards (391 ha). A conventional management program of insecticide sprays and pheromone mating disruption was supplemented with weekly releases of sterile moths for 1-6 yr. Our objective was to compare the recapture rate of sterile moths following their release by four methods, and the efficiency of each system. The methods were the following: a fixed-wing unmanned plane flying ~40-45 m high at 70 km/h, an unmanned hexacopter travelling 20 m high at 25 km/h, and manually from the ground via bicycles or motor vehicles. The different release methods were used in different years or weeks. Sterile male moths were recaptured in grids of pheromone traps positioned throughout each orchard. The highest recapture rate followed delivery by hexacopter, then bicycle, vehicle, and plane. There was a 17-fold difference in catches between releases by hexacopter and plane, and sixfold between vehicle and plane in the same season. Bicycle delivery had a 3.5-fold higher recapture rate than the plane in different years. The wind-borne horizontal drift of moths was investigated as a possible explanation for the disparity of recaptures between the two aircraft delivery systems. The methods in ascending order of time per hectare for delivery were the following: plane and vehicle, hexacopter, then bicycle. The advantages and disadvantages of each moth delivery method are discussed.

Combined Effects of Mating Disruption, Insecticides, and the Sterile Insect Technique on Cydia pomonella in New Zealand.

Codling moth was introduced into New Zealand, and remains a critical pest for the apple industry. Apples exported to some markets require strict phytosanitary measures to eliminate the risk of larval infestation. Mating disruption and insecticide applications are the principal means of suppression in New Zealand. We tested the potential for the sterile insect technique (SIT) to supplement these measures to achieve local eradication or suppression of this pest. SIT was trialed in an isolated group of six integrated fruit production (IFP) orchards and one organic orchard (total 391 ha), using sterilized insects imported from Canada, with release by unmanned aerial vehicle and from the ground. Eradication was not achieved across the region, but a very high level of codling moth suppression was achieved at individual orchards after the introduction of sterile moths in combination with mating disruption and larvicides. After six years of releases, catches of wild codling moths at three IFP orchards (224 ha) were 90-99% lower than in 2013-2014, the year before releases began. Catches at three other IFP orchards (129 ha) decreased by 67-97% from the year before releases began (2015-2016), from lower initial levels. At a certified organic orchard with a higher initial population under only organic larvicides and mating disruption, by 2019-2020, there was an 81% reduction in wild moths capture from 2016-2017, the year before releases began.

Factors Responsible for Changes in Leafroller (Lepidoptera: Tortricidae) Species Composition on Orchards and Vineyards 1974-2015, in Hawke's Bay, New Zealand.

Leafrollers are polyphagous pests whose larvae damage fruit and cause market access problems for fruit crops exported from New Zealand. Leafroller larvae and pupae were collected mainly from four fruit crops, but also from hedges, ornamental trees, and understory weeds in orchards and vineyards of Hawke's Bay, a major fruit production region. Samples were collected from 1974 to 1977 and 1993 to 2015. This timespan was divided into periods that broadly coincided with broad-spectrum insecticide management, the transition to selective insecticides, and the full implementation of integrated fruit production (IFP) programs in apples, grapes, and stone fruit. Eight tortricid species were identified, but the accidentally introduced Epiphyas postvittana (Walker) (Lepidoptera: Tortricidae) and two native species, Ctenopseustis obliquana (Walker) and Planotortrix octo Dugdale, comprised 95% of the samples. The proportions of these three species varied according to interactions between four factors: pest management regime, collection period, property location, and host plant. In the 1970s under broad-spectrum insecticide programs, the native species dominated on all hosts. By the mid-late 1990s when IFP was introduced, all the main leafroller species were in decline. However, E. postvittana declined to a lesser extent than the two native species, and consequently, it became relatively more prominent. This change in species composition was delayed in two districts where localized cases of organophosphate insecticide resistance occurred in C. obliquana and P. octo. From 2000 onwards, E. postvittana was the dominant species in all districts and on all hosts, albeit with a much-reduced pest status, except on hedges and ornamental trees where C. obliquana prevailed.

Trapping Dasinuera mali (Diptera: Cecidomyiidae) in apples.

The midge Dasineura mali (Kieffer) (Diptera: Cecidomyiidae) is a significant pest of apples (Malus spp.), and the recent identification of the female sex pheromone is enabling new direct control tactics to be considered. Direct control using male suppression will require knowledge of the frequency of multiple mating, dispersal and colonization rates, and the efficiency of male removal. Males were able to mate up to five times, with a mean of 2.7 times when presented in a 10 female-to-1 male group, designed to simulate male suppression. Male catch in response to the pheromone loading was curvilinear over 4 orders of magnitude from 3 microg to 30 mg on rubber septa. Trapping using a high-dose pheromone lure was combined with oil-based traps similar to the inexpensive New Zealand "Lynfield trap" used for tephritid surveillance, to test male suppression in young orchard blocks at 500 traps per ha. Monitoring traps indicated 96% lower catch in the treated plots compared with control plots, over 137 d. However, a lack of shoot tip infestation in both treated and untreated plots indicated limited colonization and prevented an assessment of potential population suppression. Furthermore, a contribution to these results from communication disruption cannot be ruled out. Replicated transects of frequency of infested shoots from a mature orchard across the adjacent young block confirmed that colonization by ovipositing females was essentially limited to the first 30 m.

Prospects for the control of apple leaf midge Dasineura mali (Diptera: Cecidomyiidae) by mass trapping with pheromone lures.

BACKGROUND: Apple leaf midge, Dasineura mali (Kieffer), poses quarantine issues for some apple export markets because larvae occasionally pupate in the stem end and calyx of fruit. Pheromone-baited oil-filled containers were used in 1 ha orchard plots to trap adult male D. mali in order to test the potential for mass trapping to reduce populations. RESULTS: Mass-trapped plots had 97% fewer adult males in pheromone traps and 48% fewer larvae per shoot in the second D. mali generation compared with untreated areas. Oil traps caught on average 900 000 D. mali per plot over 11 weeks during the second and third generations. Catches averaged 9200 per trap at plot corners. By comparison, catches were 51% lower 10-25 m away along borders, 80% lower at the midpoint of borders and 95% lower >7 m from plot edges. Fruit infestation was low (four out of 8000 apples). CONCLUSION: The attractiveness of the pheromone, monophagous habit and low mobility of D. mali enhance the prospects for successful mass trapping. Countering this are high populations, multivoltinism and aspects of mating behaviour. Mass trapping would probably have been more effective had it been in place season long and conducted over successive years. It needs refinements and more study before becoming a feasible control option for D. mali.

The accuracy of computed tomography to predict completeness of pulmonary fissures. A prospective study.

RATIONALE: Endobronchial valves are a potential alternative to lung volume reduction surgery for advanced emphysema. The greatest improvements in pulmonary function are seen in patients with complete pulmonary fissures, as determined by computed tomography (CT). However, the accuracy of CT to predict completeness of pulmonary fissures has not been compared with the reference standard of direct observation during thoracic surgery. OBJECTIVES: To determine the accuracy of CT scans to predict completeness of pulmonary fissures. METHODS: We conducted a double-blind, prospective trial in which completeness of pulmonary fissures was evaluated by direct observation during thoracic surgery. Preoperative CT scans were independently reviewed by two dedicated thoracic radiologists and completeness of the fissures was recorded and compared with intraoperative findings. MEASUREMENTS AND MAIN RESULTS: The fissures of 46 patients were evaluated. The positive predictive value of CT scan to detect a complete fissure was 100% for the right major fissure and 75% for the left fissure, but only 33% for the right minor fissure. CT scans had a negative predictive value of 29% in evaluation of the right major fissure. CONCLUSIONS: CT scans overestimate completeness of the right minor fissure and underestimate completeness of the right major fissure. These findings may have implications for the use of CT scans to select patients for endobronchial valve insertion.

Spatial analysis of mass trapping: how close is close enough?

BACKGROUND: The identification of new attractants can present opportunities for developing mass trapping, but standard screening methods are needed to expedite this. We have developed a simple approach based on quantifying trap interference in 4 × 4 trap arrays with different spacings. We discuss results from sex pheromones in Lepidoptera (light brown apple moth, Epiphyas postvittana), Diptera (apple leaf curling midge, Dasineura mali) and Homoptera (citrophilous mealybug, Pseudococcus calceolariae), compared with a kairomone for New Zealand flower thrips (Thrips obscuratus). RESULTS: The ratio of catch in corner traps to catch in centre traps was 25:1 at 750 D. mali traps ha(-1) , and was still ∼5:1 at 16 traps ha(-1) , suggesting trap interference even at such low trap densities. Trap competition for sex pheromone lures at close spacing (<5 m) was evident in 16-trap arrays of P. calceolariae, but less so for E. postvittana. No trap competition was observed at 4 m spacings with the kairomone for T. obscuratus. CONCLUSIONS: The ratio of catch in traps in the corner and centre of a 16-trap array at different spacings offers a rapid preliminary assessment method for determining the potential for mass trapping. Additional knowledge of vital rates and dispersal is needed for predicting population suppression. Our approach should have value in mass trapping development. © 2014 Society of Chemical Industry.

N-Butyl sulfide as an attractant and coattractant for male and female codling moth (Lepidoptera: Tortricidae).

Research to discover and develop attractants for the codling moth, Cydia pomonella L., has involved identification of the chemicals eliciting moth orientation to conspecific female moths, host fruits, fermented baits, and species of microbes. Pear ester, acetic acid, and N-butyl sulfide are among those chemicals reported to attract or enhance attractiveness to codling moth. We evaluated the trapping of codling moth with N-butyl sulfide alone and in combination with acetic acid and pear ester in apple orchards. Acetic acid was attractive in two tests and N-butyl sulfide was attractive in one of two tests. N-Butyl sulfide increased catches of codling moth when used with acetic acid to bait traps. N-Butyl sulfide also increased catches of codling moth when added to traps baited with the combination of acetic acid and pear ester. Male and female codling moth both responded to these chemicals and chemical combinations. These results provide a new three-component lure comprising N-butyl sulfide, acetic acid, and pear ester that is stronger for luring codling moth females than other attractants tested.

Definitive primary therapy in patients presenting with oligometastatic non-small cell lung cancer.

PURPOSE: Although palliative chemotherapy is the standard of care for patients with diagnoses of stage IV non-small cell lung cancer (NSCLC), patients with a small metastatic burden, "oligometastatic" disease, may benefit from more aggressive local therapy. METHODS AND MATERIALS: We identified 186 patients (26% of stage IV patients) prospectively enrolled in our institutional database from 2002 to 2012 with oligometastatic disease, which we defined as 5 or fewer distant metastatic lesions at diagnosis. Univariate and multivariable Cox proportional hazards models were used to identify patient and disease factors associated with improved survival. Using propensity score methods, we investigated the effect of definitive local therapy to the primary tumor on overall survival. RESULTS: Median age at diagnosis was 61 years of age; 51% of patients were female; 12% had squamous histology; and 33% had N0-1 disease. On multivariable analysis, Eastern Cooperate Oncology Group performance status ≥ 2 (hazard ratio [HR], 2.43), nodal status, N2-3 (HR, 2.16), squamous pathology, and metastases to multiple organs (HR, 2.11) were associated with a greater hazard of death (all P<.01). The number of metastatic lesions and radiologic size of the primary tumor were not significantly associated with overall survival. Definitive local therapy to the primary tumor was associated with prolonged survival (HR, 0.65, P=.043). CONCLUSIONS: Definitive local therapy to the primary tumor appears to be associated with improved survival in patients with oligometastatic NSCLC. Select patient and tumor characteristics, including good performance status, nonsquamous histology, and limited nodal disease, may predict for improved survival in these patients.

Natural history and molecular characteristics of lung cancers harboring EGFR exon 20 insertions.

INTRODUCTION: Exon 20 insertions are the third most common family of epidermal growth factor receptor (EGFR) mutations found in non-small-cell lung cancer (NSCLC). Little is known about cancers harboring these mutations aside from their lack of response to EGFR tyrosine kinase inhibitors, impairing the development of effective targeted therapies. METHODS: NSCLC patients with EGFR genotyping were studied using a mechanism approved by the Institutional Review Board. Cancers with exon 20 insertions were indentified, sequences were characterized, and effectiveness of different treatment regimens was reviewed retrospectively. Clinical characteristics and survival were compared with cancers harboring common EGFR mutations and cancers with wild-type EGFR. RESULTS: One thousand eighty-six patients underwent EGFR genotyping from 2004 to 2012. Twenty seven (2.5%) harbored exon 20 insertions, making up 9.2% of all cancers with documented EGFR mutations. Compared with wild-type cancers, those with exon 20 insertions were more commonly found in never-smokers and Asian patients. Insertion sequences were highly variable, with the most common variant (V769_D770insASV) making up only 22% of cases. Median survival of patients with exon 20 insertions was 16 months, similar to the survival of wild-type cancers and shorter than the survival of cancers with common EGFR mutations. CONCLUSIONS: Patients with EGFR exon 20 insertions have similar clinical characteristics to those with common EGFR mutations but a poorer prognosis. The prevalence of this subset of NSCLC is similar to that of other genotype-defined subsets of lung adenocarcinoma (e.g. those with BRAF mutations, HER2 insertions, ROS1 rearrangements) and is a population of interest for trials of new targeted therapies.