Age, operation time and surgical approach can be used to detect incidental gallbladder carcinoma in cholecystectomy specimens from low-incidence settings.

AIMS: Gallbladders resected for non-neoplastic diseases are systemically examined microscopically to rule out incidental dysplasia and carcinoma. The main aim of this study was to test whether a pre-grossing algorithm can detect incidental gallbladder carcinoma. The secondary aim was to test whether the algorithm can detect high-grade dysplasia. METHODS AND RESULTS: A retrospective study of clinical, pathological and radiological findings in cholecystectomy recipients was performed on a test set to develop a classification and regression tree algorithm. Cholecystectomy cases were included; exclusion criteria were age <18 years, missing pathology reports, preoperative suspicion of neoplastic disease, and cholecystectomy for non-gallbladder oncological disease. Five thousand nine hundred and eighty-two cholecystectomies from 2006 to 2018 were included in the study, with 18 cases of incidental gallbladder carcinoma and 11 cases of high-grade dysplasia. Three hundred and ninety controls were randomly selected for the testing set. Patient age, surgical approach, operation duration, dilatation of the biliary tract and gallbladder gross anomalies were statistically significant distinguishing factors in multivariate analysis (P < 0.00-0.026). Unsupervised testing with a conditional inference tree suggested that age, procedure type and operation duration can be used to identify incidental gallbladder carcinoma from controls, whereas high-grade dysplasia also requires grossing parameters to identify half of the cases (5/11). CONCLUSION: Readily available clinical parameters and postoperative data can be used to detect incidental gallbladder carcinoma. High-grade dysplasia mostly requires grossing and microscopic examination.

The Matrisome during Aging and Longevity: A Systems-Level Approach toward Defining Matreotypes Promoting Healthy Aging.

Accumulation of damage is generally considered the cause of aging. Interventions that delay aging mobilize mechanisms that protect and repair cellular components. Consequently, research has been focused on studying the protective and homeostatic mechanisms within cells. However, in humans and other multicellular organisms, cells are surrounded by extracellular matrices (ECMs), which are important for tissue structure, function, and intercellular communication. During aging, components of the ECM become damaged through fragmentation, glycation, crosslinking, and accumulation of protein aggregation, all of which contribute to age-related pathologies. Interestingly, placing senescent cells into a young ECM rejuvenates them. Furthermore, we found that many longevity-assurances pathways reactivate de novo synthesis of ECM proteins during aging. This raises the question of what constitutes a young ECM to reverse aging or maintain health? In order to make inroads to answering this question, I suggest a systems-level approach of quantifying the matrisome or ECM compositions reflecting health, pathology, or phenotype and propose a novel term, the "matreotype," to describe this. The matreotype is defined as the composition and modification of ECM or matrisome proteins associated with or caused by a phenotype, such as longevity, or a distinct and acute physiological state, as observed during aging or disease. Every cell type produces its unique ECM. Intriguingly, cancer-cell types can even be identified based on their unique ECM composition. Thus, the matreotype reflects cellular identity and physiological status. Defined matreotypes could be used as biomarkers or prognostic factors for disease or health status during aging with potential relevance for personalized medicine. Treatment with biologics that alter ECM-to-cell mechanotransduction might be a strategy to reverse age-associated pathologies. An understanding of how to reverse from an old to a young matreotype might point toward novel strategies to rejuvenate cells and help maintain tissue homeostasis to promote health during aging.

Untangling Longevity, Dauer, and Healthspan in Caenorhabditis elegans Insulin/IGF-1-Signalling.

The groundbreaking discovery that lower levels of insulin/IGF-1 signaling (IIS) can induce lifespan extension was reported 24 years ago in the nematode Caenorhabditis elegans. In this organism, mutations in the insulin/IGF-1 receptor gene daf-2 or other genes in this pathway can double lifespan. Subsequent work has revealed that reduced IIS (rIIS) extends lifespan across diverse species, possibly including humans. In C. elegans, IIS also regulates development into the diapause state known as dauer, a quiescent larval form that enables C. elegans to endure harsh environments through morphological adaptation, improved cellular repair, and slowed metabolism. Considerable progress has been made uncovering mechanisms that are affected by C. elegans rIIS. However, from the beginning it has remained unclear to what extent rIIS extends C. elegans lifespan by mobilizing dauer-associated mechanisms in adults. As we discuss, recent work has shed light on this question by determining that rIIS can extend C. elegans lifespan comparably through downstream processes that are either dauer-related or -independent. Importantly, these two lifespan extension programs can be distinguished genetically. It will now be critical to tease apart these programs, because each may involve different longevity-promoting mechanisms that may be relevant to higher organisms. A recent analysis of organismal "healthspan" has questioned the value of C. elegans rIIS as a paradigm for understanding healthy aging, as opposed to simply extending life. We discuss other work that argues strongly that C. elegans rIIS is indeed an invaluable model and consider the likely possibility that dauer-related processes affect parameters associated with health under rIIS conditions. Together, these studies indicate that C. elegans and analyses of rIIS in this organism will continue to provide unexpected and exciting results, and new paradigms that will be valuable for understanding healthy aging in humans.

Preliminary Experience in Combined Somatic and Cerebral Oximetry Monitoring in Liver Transplantation.

OBJECTIVE: The use of cerebral near-infrared spectroscopy (NIRS) has become widespread in cardiac surgery after research demonstrated an association between perioperative cerebral desaturations and postoperative complications. Somatic NIRS desaturation also is associated with an increased risk of postoperative complications and mortality. The objective of this study was to explore the trends of both somatic and cerebral NIRS during liver transplantation. DESIGN: A prospective, single-site, observational case series. SETTING: Tertiary care center. PARTICIPANTS: The study comprised 10 patients undergoing liver transplantation. INTERVENTIONS: NIRS sensors were placed on the forehead (cerebral regional oxygen saturation [rSO2]) and on the right arm and right leg (somatic rSO2) to measure tissue perfusion. Desaturation was defined as a 20% decrease of baseline values for 15 seconds. MEASUREMENTS AND MAIN RESULTS: In all patients, parallel changes in both cerebral and somatic rSO2 values were observed during phlebotomy, bleeding, transfusion, portal vein clamping, and the use of vasoactive agents. Induction of anesthesia increased cerebral rSO2 more than it did somatic values. However, ascites removal, abdominal manipulation, and clamping of the inferior vena cava (IVC) were associated with nonparallel changes in cerebral and somatic rSO2. Ascites removal was associated with increased somatic leg rSO2, and IVC clamping and abdominal hypertension were associated with a significant reduction in somatic leg rSO2. Somatic leg desaturation instead of arm or cerebral desaturation was associated with more postoperative complications. CONCLUSIONS: The use of combined NIRS monitoring allows for the identification of the source of somatic or cerebral desaturation. Compromised venous flow from the IVC from clamping or abdominal compartment syndrome typically is associated with the appearance of more pronounced leg than arm desaturation.

Impact of blood salvage therapy during oncologic liver surgeries on allogenic transfusion events, survival, and recurrence: an ambidirectional cohort study.

INTRODUCTION: The use of autologous blood transfusions in oncologic surgeries is somewhat controversial due to the potential risk of disease dissemination through the salvage process. On the other hand, autologous blood transfusion can prevent the potential negative effects of allogenic blood transfusions and reduce use of valuable resources. METHODS: This study included 106 adult patients who underwent oncologic liver surgery at our institution between December 2015 and June 2019. The patients were divided into two groups: the Cell Saver group (operated between January 2018 and June 2019) and the control group (operated between December 2015 and December 2017). The Cell Saver device was present in the operating room for the Cell Saver group, and blood was retransfused if a certain amount of blood loss occurred. Data analysis focused on outcomes such as blood transfusion requirements, overall survival, recurrence-free survival, hemoglobin levels, hospital stay, and complications. Patient records provided relevant information on demographics, surgery details, pathology, and outcomes for both groups. RESULTS: Autologous blood transfusion was found to reduce the amount of blood units needed (4.0 units (control group) versus 0.4 units (Cell Saver group) P =0.029. Kaplan-Meier curves showed no difference for both overall survival 471.6 days (Cell Saver group) versus 468.3 days (control group) ( P =0.219) and 488.9 days (Cell Saver group) versus 487.2 days (control group) ( P =0.993) and disease-free survival ( P =0.553) and ( P =0.735) for primary hepatic tumors and hepatic metastasis respectively between the Cell Saver and control groups. Overall survival regardless of the type of tumor was similar to the control group (485.4 days vs. 481.9 days) ( P =0.503). Survival was significantly lower for minor hepatectomies (516.0 days vs. 517.4 days) ( P =0.050) in the Cell Saver group, major hepatectomies showed no difference in overall survival (470.2 days vs. 466.4 days) ( P =0.868). No impact on disease recurrence was found between patients who received autologous blood transfusions versus those who did not. CONCLUSION: The use of Cell Saver should not be avoided in oncologic surgeries of the liver. Use of Cell Saver for major hepatectomies might be more beneficial as OS was significantly lower for the Cell Saver group for patients who underwent minor hepactomies. Further research is needed to explain this conflicting result. Nonetheless, the use of Cell Saver in autologous blood transfusions can reduce the use of valuable resources and the risks associated with allogenic blood transfusions.

Malignant duodenal gastrointestinal neuroectodermal tumor (GNET): Case report and review of the literature.

INTRODUCTION: Malignant gastrointestinal neuroectodermal tumor (GNET) is a rare malignancy primarily affecting the gastrointestinal tract. Upon cross-sectional imaging, it can be easily confused with other mesenchymal tumors. This article presents a case of duodenal GNET and reviews the current literature on this rare entity. PRESENTATION OF CASE: A 73-year-old female patient presented with a 4 cm duodenal mass on CT scan. With a presumptive diagnosis of GIST, a D3-D4 duodenectomy with cholecystectomy were performed. Subsequent pathological analysis of the surgical specimen revealed a 4.5 cm malignant gastrointestinal neuroectodermal tumor (GNET), also known as clear cell sarcoma-like gastrointestinal tumor (CCSLGT). DISCUSSION: While there are less than 115 cases of GNET reported worldwide, prognosis is usually poor with a 50 % survival at 3 years, and mortality rate described is as high as 75 %. To the authors' knowledge, this duodenal GNET case represents the first one ever described for this location. CONCLUSION: Early recognition of GNET is essential due to its poor prognosis and its ability to metastasize. Awareness of its existence and diagnostic criteria by every member of the medical team is key to obtain optimal patient care.

Undifferentiated carcinoma of the pancreas with osteoclast-like giant cells, a two cases report.

INTRODUCTION AND IMPORTANCE: Fine needle aspiration is the standard method for the pathological evaluation of pancreatic masses. In the following context, rare variants of such masses might present a challenge. Our goal is to describe the clinical, cytological, and histological findings of two cases of undifferentiated carcinoma with osteoclast-like giant cells (UCOCGC) a rare variant of pancreatic ductal adenocarcinoma (PDAC). CASE PRESENTATION: Two cases were identified. Cytological findings exhibit similarities between the two cases. One patient received multiple chemotherapy regimens and a surgery and recurred within three years of diagnosis, while the other succumbed to cholangitis resulting from hepatic metastases a year after their initial surgery. DISCUSSION: UCOCGC is a rare variant of pancreatic cancer, characterized by a unique cytological aspect. Recognizing this variant is essential considering its distinct prognosis compared to usual pancreatic adenocarcinoma. CONCLUSION: We presented two cases of UCOCGC a rare pancreatic cancer variant, exposing diagnostic particularities and clinical evolution.

Colorectal cancer hepatic metastases resection margins outcomes: a single-centre retrospective cohort study.

Background: Surgical resection is the most efficient treatment for isolated colorectal cancer hepatic metastases. Among the known prognostic factors of this procedure, the impact of the resection margin width is still a controversial matter in the literature. Methods: A retrospective cohort study was performed including 170 patients who underwent surgical resection of colorectal cancer liver metastases (CRLMs) between 2006 and 2016 in our hepatobiliary unit. Resection margin width was determined histologically by measuring the distance from the tumour in millimetres or centimetres. Patients' clinical characteristics were also collected. Patients were then stratified in two tumour margin groups: below 5 mm (group A) and equal to or above 5 mm (group B). Overall survival (OS) and disease-free survival (DFS) were the primary outcomes. Results: Kaplan-Meier curves showed significantly better outcomes for cases having resection margins above 5 mm for both DFS with 1508.7 days (range 1151.2-1866.2) in group A, compared to 2463.9 days (range 2021.3-2906.5) in group B (P=0.049), and OS with 1557.8 days (range 1276.3-1839.3) for group A and 2303.8 days (range 1921.2--2686.4) for group B (P=0.020). This survival benefit was not significant for patients presenting with stage IV CRC at diagnosis or cases where extended (7+ segments) resections were performed. Conclusion: Five-millimetre margins provide a significant survival advantage and should be aimed for in the treatment of CRLMs. Further research on the cause for this finding, including tumour biology's impact on survival, is required.

Perioperative oncolytic virotherapy to counteract surgery-induced immunosuppression and improve outcomes in pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is a high fatality cancer with one of the worst prognoses in solid tumors. Most patients present with late stage, metastatic disease and are not eligible for potentially curative surgery. Despite complete resection, the majority of surgical patients will recur within the first two years following surgery. Postoperative immunosuppression has been described in different digestive cancers. While the underlying mechanism is not fully understood, there is compelling evidence to link surgery with disease progression and cancer metastasis in the postoperative period. However, the idea of surgery-induced immunosuppression as a facilitator of recurrence and metastatic spread has not been explored in the context of pancreatic cancer. By surveying the existing literature on surgical stress in mostly digestive cancers, we propose a novel practice-changing paradigm: alleviate surgery-induced immunosuppression and improve oncological outcome in PDAC surgical patients by administering oncolytic virotherapy in the perioperative period.

Removal of extracellular human amyloid beta aggregates by extracellular proteases in C. elegans.

The amyloid beta (Aß) plaques found in Alzheimer's disease (AD) patients' brains contain collagens and are embedded extracellularly. Several collagens have been proposed to influence Aß aggregate formation, yet their role in clearance is unknown. To investigate the potential role of collagens in forming and clearance of extracellular aggregates in vivo, we created a transgenic Caenorhabditis elegans strain that expresses and secretes human Aß1-42. This secreted Aß forms aggregates in two distinct places within the extracellular matrix. In a screen for extracellular human Aß aggregation regulators, we identified different collagens to ameliorate or potentiate Aß aggregation. We show that a disintegrin and metalloprotease a disintegrin and metalloprotease 2 (ADM-2), an ortholog of ADAM9, reduces the load of extracellular Aß aggregates. ADM-2 is required and sufficient to remove the extracellular Aß aggregates. Thus, we provide in vivo evidence of collagens essential for aggregate formation and metalloprotease participating in extracellular Aß aggregate removal.

Phlebotomy resulting in controlled hypovolemia to prevent blood loss in major hepatic resections (PRICE-2): study protocol for a phase 3 randomized controlled trial.

INTRODUCTION: Blood loss and red blood cell (RBC) transfusion in liver surgery are areas of concern for surgeons, anesthesiologists, and patients alike. While various methods are employed to reduce surgical blood loss, the evidence base surrounding each intervention is limited. Hypovolemic phlebotomy, the removal of whole blood from the patient without volume replacement during liver transection, has been strongly associated with decreased bleeding and RBC transfusion in observational studies. This trial aims to investigate whether hypovolemic phlebotomy is superior to usual care in reducing RBC transfusions in liver resection. METHODS: This study is a double-blind multicenter randomized controlled trial. Adult patients undergoing major hepatic resections for any indication will be randomly allocated in a 1:1 ratio to either hypovolemic phlebotomy and usual care or usual care alone. Exclusion criteria will be minor resections, preoperative hemoglobin <100g/L, renal insufficiency, and other contraindication to hypovolemic phlebotomy. The primary outcome will be the proportion of patients receiving at least one allogeneic RBC transfusion unit within 30 days of the onset of surgery. Secondary outcomes will include transfusion of other allogeneic blood products, blood loss, morbidity, mortality, and intraoperative physiologic parameters. The surgical team will be blinded to the intervention. Randomization will occur on the morning of surgery. The sample size will comprise 440 patients. Enrolment will occur at four Canadian academic liver surgery centers over a 4-year period. Ethics approval will be obtained at participating sites before enrolment. DISCUSSION: The results of this randomized control trial will provide high-quality evidence regarding the use of hypovolemic phlebotomy in major liver resection and its effects on RBC transfusion. If proven to be effective, this intervention could become standard of care in liver operations internationally and become incorporated within perioperative patient blood management programs. TRIAL REGISTRATION: ClinicalTrials.gov NCT03651154 . Registered on August 29 2018.

An unusual case of pancreatitis revealing a metachronous renal cell carcinoma metastasis to the gallbladder.

Clear-cell renal cell carcinoma (RCC) is a common urological tumor known for its potential to metastasize. Common sites of metastasis include the lungs, lymph nodes, liver and bones but rare sites of metastasis are described. Gallbladder metastasis from RCC is very rare and occurs mostly in men. It is admitted that most cases are asymptomatic. Cholecystectomy has been performed as the treatment for solitary lesion. We describe a case of RCC metastasis diagnosed after lithiasic pancreatitis in a 68-year-old male. To our knowledge, this is the first case of a metachronous RCC metastasis to the gallbladder presenting concurrently with lithiasic pancreatitis.

Transperitoneal laparoscopic radical nephrectomy after multiple previous abdominal surgeries and intraperitoneal hyperthermic chemotherapy: a case report.

Laparoscopic indications are still growing due to the acquisition and development of new skills and expertise in the laparoscopic field. We report the first case of a successful transperitoneal right radical nephrectomy after intraperitoneal hyperthermic chemotherapy in a 56-year-old female who previously underwent multiple abdominal surgeries for appendicular adenocarcinoma with pseudomyxoma peritonei. In patients with multiples previous abdominal surgeries and intraperitoneal chemotherapy, transperitoneal laparoscopic surgeries are feasible in experienced hands. However, patient safety is paramount and conversion to open surgery should always be considered in case of complications.

Combined cerebral and somatic near-infrared spectroscopy oximetry monitoring during liver surgery: an observational and non-interventional study.

BACKGROUND: Cerebral oximetry using near-infrared spectroscopy (NIRS) is used for monitoring cerebral oxygen saturation during cardiac surgery and is correlated with clinical outcomes. Our goal was to explore cerebral and somatic NIRS in liver resections as a predictor of post-operative complications. METHODS: Prospective observational and non-interventional study from a tertiary care university hospital including adult patients undergoing liver resection monitored using NIRS at four sites before and during surgery. Those sites were: frontotemporal left and right zones, right thigh, and right arm. Anesthesiologists and surgeons were blinded to oximetry values. Correlations were assessed between baseline oximetry values and cerebro-somatic desaturation load (threshold of 80% from baseline) values with peri-operative events and complications. RESULTS: Ninety patients were distributed equally among gender with a mean age of 59.7 ± 13.1 years. Lower baseline cerebral and/or somatic values were associated with increased risk of delirium, respiratory failure, surgical and renal complications, blood transfusions, and length of stay in the intensive care unit and in the hospital (P < 0.05). The severity of somatic desaturation below 80% was the only parameter associated with blood losses (P = 0.030) and length of hospital stay (P = 0.047). CONCLUSIONS: Cerebral and somatic desaturation does occur in liver resection and can be used simultaneously during liver surgery. Both baseline cerebral and somatic NIRS values are correlated with complications and outcomes. However, thigh desaturation appears more sensitive than cerebral NIRS values in predicting some of these complications.

End-of-life targeted degradation of DAF-2 insulin/IGF-1 receptor promotes longevity free from growth-related pathologies.

Preferably, lifespan-extending therapies should work when applied late in life without causing undesired pathologies. Reducing insulin/insulin-like growth factor (IGF)-1 signaling (IIS) increases lifespan across species, but the effects of reduced IIS interventions in extreme geriatric ages remains unknown. Using the nematode Caenorhabditis elegans, we engineered the conditional depletion of the DAF-2/insulin/IGF-1 transmembrane receptor using an auxin-inducible degradation (AID) system. This allowed for the temporal and spatial reduction in DAF-2 protein levels at time points after which interventions such as RNAi become ineffective. Using this system, we found that AID-mediated depletion of DAF-2 protein surpasses the longevity of daf-2 mutants. Depletion of DAF-2 during early adulthood resulted in multiple adverse phenotypes, including growth retardation, germline shrinkage, egg retention, and reduced brood size. By contrast, AID-mediated depletion of DAF-2 post-reproduction, or specifically in the intestine in early adulthood, resulted in an extension of lifespan without these deleterious effects. Strikingly, at geriatric ages, when 75% of the population had died, AID-mediated depletion of DAF-2 protein resulted in a doubling in lifespan. Thus, we provide a proof-of-concept that even close to the end of an individual's lifespan, it is possible to slow aging and promote longevity.

The goal of geroscience, or research into old age, is to promote health during old age, and thus, to increase lifespan. In the body, the groups of biochemical reactions, or 'pathways', that allow an organism to sense nutrients, and regulate growth and stress, play major roles in ensuring healthy aging. Indeed, organisms that do not produce a working version of the insulin/IGF-1 receptor, a protein involved in one such pathway, show increased lifespan. In the worm Caenorhabditis elegans, mutations in the insulin/IGF-1 receptor can even double their lifespan. However, it is unclear whether this increase can be achieved once the organism has reached old age. To answer this question, Venz et al. genetically engineered the nematode worm C. elegans so that they could trigger the rapid degradation of the insulin/IGF-1 receptor either in the entire organism or in a specific tissue. Venz et al. started by aging several C. elegans worms for three weeks, until about 75% had died. At this point, they triggered the degradation of the insulin/IGF-1 receptor in some of the remaining worms, keeping the rest untreated as a control for the experiment. The results showed that the untreated worms died within a few days, while worms in which the insulin/IGF-1 receptor had been degraded lived for almost one more month. This demonstrates that it is possible to double the lifespan of an organism at the very end of life. Venz et al.'s findings suggest that it is possible to make interventions to extend an organism's lifespan near the end of life that are as effective as if they were performed when the organism was younger. This sparks new questions regarding the quality of this lifespan extension: do the worms become younger with the intervention, or is aging simply slowed down?

Portal vein embolization does not affect the long-term survival and risk of cancer recurrence among colorectal liver metastases patients: A prospective cohort study.

BACKGROUND: Previous studies comparing the survival outcomes of liver resections with and without preoperative portal vein embolization (PVE) for colorectal liver metastases (CLM) have linked PVE to higher rate of tumor progression, lower overall survival (OS) and lower disease-free survival (DFS). The lack of adjusted models to compare these outcomes is a limitation of these studies since patients requiring PVE may differ significantly from the ones receiving upfront surgery. MATERIALS AND METHODS: Prospective cohort study of 128 patients undergoing CLM resection. The OS analysis followed an intent-to-treat (ITT) approach. The adjusted impact of PVE on OS and DFS was evaluated using multivariate Cox regression models. RESULTS: Seventy-one patients underwent PVE before attempting a liver resection while 57 received upfront surgery (NoPVE). All NoPVE patients were resected while 14 PVE participants (19.7%) were not operated (tumor progression = 9/14). PVE patients had a significantly higher preoperative lesions count (3 [1.75-4] vs 1 [1-2.5]; p < 0.001), a higher prevalence of bilateral metastases (23.5% vs 8.8, p = 0.028) and a higher count of neo-adjuvant chemotherapy cycles compared to NoPVE patients. The OS of PVE patients was similar to NoPVE participants (44.7 months [26.9-69.5] vs 49.0 [24.9-64.8], p = 0.761). The DFS of resected PVE patients was higher than NoPVE patients (33.2 months [10.7-54.6] vs 23.4 months [14.1-58.1], p = 0.991). In the adjusted models, preoperative lesions count was the only significant predictor of overall mortality (HR+IC95 = 1.06 (1.02-1.11) p = 0.005) and cancer recurrence (HR+IC95 = 1.14 (1.03-1.27) p = 0.012). CONCLUSION: In the context of CLM, patients requiring PVE differ significantly from patients receiving upfront surgery. This confirms the need for adjusted models when comparing the clinical outcomes of both groups. Our adjusted analysis suggests that PVE is not a significant predictor of a lower OS or DFS. PVE allowed the resection of 80% of participants with initially unresectable CLM. INSTITUTIONAL PROTOCOL NUMBER: 12.106 STUDY REGISTRATION NUMBER: NCT03168230.

Oxidative Stress Assays (arsenite and tBHP) in Caenorhabditis elegans.

Cells and organisms face constant exposure to reactive oxygen species (ROS), either from the environment or as a by-product from internal metabolic processes. To prevent cellular damage from ROS, cells have evolved detoxification mechanisms. The activation of these detoxification mechanisms and their downstream responses represent an overlapping defense response that can be tailored to different sources of ROS to adequately adapt and protect cells. In this protocol, we describe how to measure the sensitivity to oxidative stress from two different sources, arsenite and tBHP, using the nematode C. elegans.

NADPH oxidase-mediated redox signaling promotes oxidative stress resistance and longevity through memo-1 in C. elegans.

Transient increases in mitochondrially-derived reactive oxygen species (ROS) activate an adaptive stress response to promote longevity. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidases produce ROS locally in response to various stimuli, and thereby regulate many cellular processes, but their role in aging remains unexplored. Here, we identified the C. elegans orthologue of mammalian mediator of ErbB2-driven cell motility, MEMO-1, as a protein that inhibits BLI-3/NADPH oxidase. MEMO-1 is complexed with RHO-1/RhoA/GTPase and loss of memo-1 results in an enhanced interaction of RHO-1 with BLI-3/NADPH oxidase, thereby stimulating ROS production that signal via p38 MAP kinase to the transcription factor SKN-1/NRF1,2,3 to promote stress resistance and longevity. Either loss of memo-1 or increasing BLI-3/NADPH oxidase activity by overexpression is sufficient to increase lifespan. Together, these findings demonstrate that NADPH oxidase-induced redox signaling initiates a transcriptional response that protects the cell and organism, and can promote both stress resistance and longevity.

Adrenal metastasis of a phyllodes tumor of the breast: Case report and review of the literature.

INTRODUCTION: A phyllodes tumor is a neoplasm of mixed mesenchymal and epithelial origin affecting the breast. It may pursue a benign or malignant evolution with distant metastases in the latter case. Sites most commonly affected by metastases are the lungs and bones. Simple mastectomy is the mainstay of treatment. This article presents the first described case of metastasis to the adrenal gland after sarcomatous transformation of a phyllodes tumor. A review of the literature is presented afterwards. PRESENTATION OF CASE: A 57-year old female patient presented with a voluminous breast mass which was completely resected. Unfortunately she presented with malignant recurrence in the breast which was also resected. A later recurrence within the lung presented and was completely resected but showed aspects of sarcomatous changes. Finally a recurrence was pathologically documented within the adrenal gland. Unfortunately, disease later progressed and the patient refused further treatment at that point. DISCUSSION: While malignant transformation of breast phyllodes tumors and metastasis is relatively common, the prognosis for initially benign lesion that are completely excised is usually good. This case represents the first documented metastasis to the adrenal gland of a breast phyllodes tumor. CONCLUSION: We presented the first case of adrenal metastasis of a phyllodes tumor after sarcomatous degeneration. This is an unusual presentation of a relatively uncommon but well-recognized disease of variable malignant potential.