Influence of Melissa officinalis essential oil and its formulation on Typhlodromips swirskii and Neoseiulus barkeri (Acari: Phytoseiidae)

The toxicity of Melissa officinalis L. essential oil and its formulation (Melissacide) were evaluated against eggs and females of two predatory phytoseiid mites, Typhlodromips swirskii (Athias Henriot) and Neoseiulus barkeri (Hughes), using direct spray. Results indicate that both tested materials were potent on predatory females than egg stage. Typhlodromips swirskii was proved to be more sensitive to the oil and formulation than N. barkeri. Females mortality were (62-100%) in T. swirskii, and (46-69%) in N. barkeri, when both predatory mites were sprayed with LC50 and LC90 of the oil and Melissacide reported on Tetranychus urticae Koch. Females of both predators were suffered from reduction in food consumption when sprayed with two sublethal concentrations of Melissacide, while insignificant differences reported in daily number of eggs deposited by females of T. swirskii, when sprayed with its LC25 value of Melissacide and control

The Origin and Contribution of Cancer-Associated Fibroblasts in Colorectal Carcinogenesis

Background & Aims: Cancer-associated fibroblasts (CAFs) play an important role in colorectal cancer (CRC) progression and predict poor prognosis in CRC patients. However, the cellular origins of CAFs remain unknown, making it challenging to therapeutically target these cells. Here, we aimed to identify the origins and contribution of colorectal CAFs associated with poor prognosis. Methods: To elucidate CAF origins, we used a colitis-associated CRC mouse model in 5 different fate-mapping mouse lines with 5-bromodeoxyuridine dosing. RNA sequencing of fluorescence-activated cell sorting–purified CRC CAFs was performed to identify a potential therapeutic target in CAFs. To examine the prognostic significance of the stromal target, CRC patient RNA sequencing data and tissue microarray were used. CRC organoids were injected into the colons of knockout mice to assess the mechanism by which the stromal gene contributes to colorectal tumorigenesis. Results: Our lineage-tracing studies revealed that in CRC, many ACTA2+ CAFs emerge through proliferation from intestinal pericryptal leptin receptor (Lepr)+ cells. These Lepr-lineage CAFs, in turn, express melanoma cell adhesion molecule (MCAM), a CRC stroma-specific marker that we identified with the use of RNA sequencing. High MCAM expression induced by transforming growth factor β was inversely associated with patient survival in human CRC. In mice, stromal Mcam knockout attenuated orthotopically injected colorectal tumoroid growth and improved survival through decreased tumor-associated macrophage recruitment. Mechanistically, fibroblast MCAM interacted with interleukin-1 receptor 1 to augment nuclear factor κB–IL34/CCL8 signaling that promotes macrophage chemotaxis. Conclusions: In colorectal carcinogenesis, pericryptal Lepr-lineage cells proliferate to generate MCAM+ CAFs that shape the tumor-promoting immune microenvironment. Preventing the expansion/differentiation of Lepr-lineage CAFs or inhibiting MCAM activity could be effective therapeutic approaches for CRC

Comparison of RCAS1 and metallothionein expression and the presence and activity of immune cells in human ovarian and abdominal wall endometriomas

BACKGROUND: The coexistence of endometrial and immune cells during decidualization is preserved by the ability of endometrial cells to regulate the cytotoxic immune activity and their capability to be resistant to immune-mediated apoptosis. These phenomena enable the survival of endometrial ectopic cells. RCAS1 is responsible for regulation of cytotoxic activity. Metallothionein expression seems to protect endometrial cells against apoptosis. The aim of the present study was to evaluate RCAS1 and metallothionein expression in human ovarian and scar endometriomas in relation to the presence of immune cells and their activity. METHODS: Metallothionein, RCAS1, CD25, CD69, CD56, CD16, CD68 antigen expression was assessed by immunohistochemistry in ovarian and scar endometriomas tissue samples which were obtained from 33 patients. The secretory endometrium was used as a control group (15 patients). RESULTS: The lowest metallothionein expression was revealed in ovarian endometriomas in comparison to scar endometriomas and to the control group. RCAS1 expression was at the highest level in the secretory endometrium and it was at comparable levels in ovarian and scar endometriomas. Similarly, the number of CD56-positive cells was lower in scar and ovarian endometriomas than in the secretory endometrium. The highest number of macrophages was found in ovarian endometriomas. RCAS1-positive macrophages were observed only in ovarian endometriomas. CD25 and CD69 antigen expression was higher in scar and ovarian endometriomas than in the control group. CONCLUSION: The expression of RCAS1 and metallothionein by endometrial cells may favor the persistence of these cells in ectopic localization both in scar following cesarean section and in ovarian endometriosis

Perioperative management and anaesthetic considerations in pelvic exenterations using Delphi methodology: Results from the PelvEx Collaborative

Background: The multidisciplinary perioperative and anaesthetic management of patients undergoing pelvic exenteration is essential for good surgical outcomes. No clear guidelines have been established, and there is wide variation in clinical practice internationally. This consensus statement consolidates clinical experience and best practice collectively, and systematically addresses key domains in the perioperative and anaesthetic management. Methods: The modified Delphi methodology was used to achieve consensus from the PelvEx Collaborative. The process included one round of online questionnaire involving controlled feedback and structured participant response, two rounds of editing, and one round of web-based voting. It was held from December 2019 to February 2020. Consensus was defined as more than 80 per cent agreement, whereas less than 80 per cent agreement indicated low consensus. Results: The final consensus document contained 47 voted statements, across six key domains of perioperative and anaesthetic management in pelvic exenteration, comprising preoperative assessment and preparation, anaesthetic considerations, perioperative management, anticipating possible massive haemorrhage, stress response and postoperative critical care, and pain management. Consensus recommendations were developed, based on consensus agreement achieved on 34 statements. Conclusion: The perioperative and anaesthetic management of patients undergoing pelvic exenteration is best accomplished by a dedicated multidisciplinary team with relevant domain expertise in the setting of a specialized tertiary unit. This consensus statement has addressed key domains within the framework of current perioperative and anaesthetic management among patients undergoing pelvic exenteration, with an international perspective, to guide clinical practice, and has outlined areas for future clinical research

Changing outcomes following pelvic exenteration for locally advanced and recurrent rectal cancer

Background Pelvic exenteration for locally advanced rectal cancer (LARC) and locally recurrent rectal cancer (LRRC) is technically challenging but increasingly performed in specialist centres. The aim of this study was to compare outcomes of exenteration over time. Methods This was a multicentre retrospective study of patients who underwent exenteration for LARC and LRRC between 2004 and 2015. Surgical outcomes, including rate of bone resection, flap reconstruction, margin status and transfusion rates, were examined. Outcomes between higher- and lower-volume centres were also evaluated. Results Some 2472 patients underwent pelvic exenteration for LARC and LRRC across 26 institutions. For LARC, rates of bone resection or flap reconstruction increased from 2004 to 2015, from 3.5 to 12.8 per cent, and from 12.0 to 29.4 per cent respectively. Fewer units of intraoperative blood were transfused over this interval (median 4 to 2 units; P = 0.040). Subgroup analysis showed that bone resection and flap reconstruction rates increased in lower- and higher-volume centres. R0 resection rates significantly increased in low-volume centres but not in high-volume centres over time (low-volume: from 62.5 to 80.0 per cent, P = 0.001; high-volume: from 83.5 to 88.4 per cent, P = 0.660). For LRRC, no significant trends over time were observed for bone resection or flap reconstruction rates. The median number of units of intraoperative blood transfused decreased from 5 to 2.5 units (P < 0.001). R0 resection rates did not increase in either low-volume (from 51.7 to 60.4 per cent; P = 0.610) or higher-volume (from 48.6 to 65.5 per cent; P = 0.100) centres. No significant differences in length of hospital stay, 30-day complication, reintervention or mortality rates were observed over time. Conclusion Radical resection, bone resection and flap reconstruction rates were performed more frequently over time, while transfusion requirements decreased

Contemporary Management of Locally Advanced and Recurrent Rectal Cancer: Views from the PelvEx Collaborative

Pelvic exenteration is a complex operation performed for locally advanced and recurrent pelvic cancers. The goal of surgery is to achieve clear margins, therefore identifying adjacent or involved organs, bone, muscle, nerves and/or vascular structures that may need resection. While these extensive resections are potentially curative, they can be associated with substantial morbidity. Recently, there has been a move to centralize care to specialized units, as this facilitates better multi-disciplinary care input. Advancements in pelvic oncology and surgical innovation have redefined the boundaries of pelvic exenterative surgery. Combined with improved neoadjuvant therapies, advances in diagnostics, and better reconstructive techniques have provided quicker recovery and better quality of life outcomes, with improved survival This article provides highlights of the current management of advanced pelvic cancers in terms of surgical strategy and potential future developments

Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

Background Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide.Methods A multimethods analysis was performed as part of the GlobalSurg 3 study-a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital.Findings Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3.85 [95% CI 2.58-5.75]; p&lt;0.0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63.0% vs 82.7%; OR 0.35 [0.23-0.53]; p&lt;0.0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer.Interpretation Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised

Induction chemotherapy followed by chemoradiotherapy versus chemoradiotherapy alone as neoadjuvant treatment for locally recurrent rectal cancer: Study protocol of a multicentre, open-label, parallel-arms, randomized controlled study (PelvEx II)

Background: A resection with clear margins (R0 resection) is the most important prognostic factor in patients with locally recurrent rectal cancer (LRRC). However, this is achieved in only 60 per cent of patients. The aim of this study is to investigate whether the addition of induction chemotherapy to neoadjuvant chemo(re)irradiation improves the R0 resection rate in LRRC. Methods: Thismulticentre, international, open-label, phase III, parallel-arms study will enrol 364 patients with resectable LRRC after previous partial or total mesorectal resection without synchronous distant metastases or recent chemo- and/or radiotherapy treatment. Patients will be randomized to receive either induction chemotherapy (three 3-week cycles of CAPOX (capecitabine, oxaliplatin), four 2- week cycles of FOLFOX (5-fluorouracil, leucovorin, oxaliplatin) or FOLFORI (5-fluorouracil, leucovorin, irinotecan)) followed by neoadjuvant chemoradiotherapy and surgery (experimental arm) or neoadjuvant chemoradiotherapy and surgery alone (control arm). Tumours will be restaged usingMRI and, in the experimental arm, a further cycle of CAPOX or two cycles of FOLFOX/FOLFIRI will be administered before chemoradiotherapy in case of stable or responsive disease. The radiotherapy dose will be 25 × 2.0 Gy or 28 × 1.8Gy in radiotherapy-naive patients, and 15 × 2.0Gy in previously irradiated patients. The concomitant chemotherapy agent will be capecitabine administered twice daily at a dose of 825mg/m2 on radiotherapy days. The primary endpoint of the study is the R0 resection rate. Secondary endpoints are long-termoncological outcomes, radiological and pathological response, toxicity, postoperative complications, costs, and quality of life. Discussion: This trial protocol describes the PelvEx II study. PelvEx II, designed as a multicentre, open-label, phase III, parallel-arms study, is the first randomized study to compare induction chemotherapy followed by neoadjuvant chemo(re)irradiation and surgery with neoadjuvant chemo(re)irradiation and surgery alone in patients with locally recurrent rectal cancer, with the aim of improving the number of R0 resections

Elective Cancer Surgery in COVID-19-Free Surgical Pathways During the SARS-CoV-2 Pandemic: An International, Multicenter, Comparative Cohort Study.

PURPOSE: As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19-free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS: This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19-free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS: Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19-free surgical pathways. Patients who underwent surgery within COVID-19-free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19-free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score-matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19-free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION: Within available resources, dedicated COVID-19-free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks