CD56 Expression Marks Human Group 2 Innate Lymphoid Cell Divergence from a Shared NK Cell and Group 3 Innate Lymphoid Cell Developmental Pathway.

According to the established model of murine innate lymphoid cell (ILC) development, helper ILCs develop separately from natural killer (NK) cells. However, it is unclear how helper ILCs and NK cells develop in humans. Here we elucidated key steps of NK cell, ILC2, and ILC3 development within human tonsils using ex vivo molecular and functional profiling and lineage differentiation assays. We demonstrated that while tonsillar NK cells, ILC2s, and ILC3s originated from a common CD34-CD117+ ILC precursor pool, final steps of ILC2 development deviated independently and became mutually exclusive from those of NK cells and ILC3s, whose developmental pathways overlapped. Moreover, we identified a CD34-CD117+ ILC precursor population that expressed CD56 and gave rise to NK cells and ILC3s but not to ILC2s. These data support a model of human ILC development distinct from the mouse, whereby human NK cells and ILC3s share a common developmental pathway separate from ILC2s.

PRMT5 supports multiple oncogenic pathways in mantle cell lymphoma.

Mantle cell lymphoma (MCL) is an incurable B-cell malignancy with an overall poor prognosis, particularly for patients that progress on targeted therapies. Novel, more durable treatment options are needed for patients with MCL. Protein arginine methyltransferase 5 (PRMT5) is overexpressed in MCL and plays an important oncogenic role in this disease via epigenetic and posttranslational modification of cell cycle regulators, DNA repair genes, components of prosurvival pathways, and RNA splicing regulators. The mechanism of targeting PRMT5 in MCL remains incompletely characterized. Here, we report on the antitumor activity of PRMT5 inhibition in MCL using integrated transcriptomics of in vitro and in vivo models of MCL. Treatment with a selective small-molecule inhibitor of PRMT5, PRT-382, led to growth arrest and cell death and provided a therapeutic benefit in xenografts derived from patients with MCL. Transcriptional reprograming upon PRMT5 inhibition led to restored regulatory activity of the cell cycle (p-RB/E2F), apoptotic cell death (p53-dependent/p53-independent), and activation of negative regulators of B-cell receptor-PI3K/AKT signaling (PHLDA3, PTPROt, and PIK3IP1). We propose pharmacologic inhibition of PRMT5 for patients with relapsed/refractory MCL and identify MTAP/CDKN2A deletion and wild-type TP53 as biomarkers that predict a favorable response. Selective targeting of PRMT5 has significant activity in preclinical models of MCL and warrants further investigation in clinical trials.

The Association of Change in Weight During Radiotherapy Treatment With Clinical Outcomes in Patients With Stage I-III Esophageal Cancer.

Esophageal carcinoma (EC) and nutritional status are strongly linked due to swallowing disruptions and treatment-related toxicities. Therefore, malnutrition and weight loss (WL) occur in 85% and 79% of EC patients, respectively. WL is frequently associated with worse EC patient outcomes, however, WL during radiation therapy (RT) and EC patient outcomes have not been well established. The purpose of this study is to retrospectively review the association of WL during RT treatment of EC with clinical outcomes. Non-metastatic EC patients from our institution treated between 2010 and 2018, receiving total prescribed dose >40 Gy and aged >18 years, were included. Patients were analyzed by WL during RT, with categories of ≥5% vs. <5% and ≥10% vs. <10%. Patient characteristics and treatment regimens were similar across all WL groups. In univariate analysis, ≥5% and ≥10% WL were significantly associated with both worse overall survival (OS) and progression-free survival (PFS), and ≥10% WL was significantly associated with increased local recurrence. In multivariate analysis, ≥5% WL was significantly associated with OS and PFS. With both ≥5% and ≥10% WL throughout the radiation treatment being detrimental to OS and PFS. The importance of nutritional support in EC patients receiving radiotherapy is further validated.

Notch Regulates Innate Lymphoid Cell Plasticity during Human NK Cell Development.

Human NK cells develop in tonsils through discrete NK cell developmental intermediates (NKDIs), yet the mechanistic regulation of this process is unclear. We demonstrate that Notch activation in human tonsil-derived stage 3 (CD34-CD117+CD94-NKp80-) and 4A (CD34-CD117+/-CD94+NKp80-) NKDIs promoted non-NK innate lymphoid cell differentiation at the expense of NK cell differentiation. In contrast, stage 4B (CD34-CD117+/-CD94+NKp80+) NKDIs were NK cell lineage committed despite Notch activation. Interestingly, whereas NK cell functional maturation from stage 3 and 4A NKDIs was independent of Notch activation, the latter was required for high NKp80 expression and a stage 4B-like phenotype by the NKDI-derived NK cells. The Notch-dependent effects required simultaneous engagement with OP9 stromal cells and were also stage-specific, with NOTCH1 and NOTCH2 receptors regulating stage 3 NKDIs and NOTCH1 primarily regulating stage 4A NKDIs. These data establish stage-specific and stromal-dependent roles for Notch in regulating human NK cell developmental plasticity and maturation.

Excision of Deep Endometriosis of the Rectosigmoid: Individualizing Care to the Presenting Pathology.

STUDY OBJECTIVE: To highlight different surgical approaches for managing deep infiltrating endometriosis involving the rectosigmoid colon. DESIGN: Demonstration of specific surgical techniques with educational narrated video footage. SETTING: Bowel endometriosis is reported in 3.8% to 37% of patients with endometriosis [1]. Most commonly, the rectosigmoid colon is involved. Pelvic ultrasound and magnetic resonance imaging may be useful in diagnosis and for surgical planning [2]. Treatment options include observation, medications, or surgery. There are various surgical techniques that can be used for excision of deep infiltrating endometriosis involving the rectosigmoid colon. Serosal shaving, discoid resection, and complete resection are the possible types of surgical interventions that are demonstrated in this surgical education video at an academic medical center. Serosal shaving is used for lesions with minimal involvement of the muscularis. It can be done sharply or with electrosurgery and it is imperative to assess bowel integrity after shaving. Discoid resection is used for lesions with muscularis involvement, <3 cm in size, and encompassing less than one-third to a half of the bowel circumference. Full-thickness discoid bowel resection can be done in various ways including manual resection with primary suture closure, regular stapler transabdominally, or EEA stapler (Medtronic EEA Circular Stapler, Minneapolis, MN) transrectally. Segmental resection is used for lesions >3 cm in size, involving >50% of the bowel circumference, or for multifocal lesions. Various suture and stapler methods exist for this technique. INTERVENTIONS: Based on the imaging and intraoperative findings, a surgical technique was chosen and demonstrated. The types of surgical techniques demonstrated include laparoscopic serosal shaving, discoid resection with manual resection and primary suture closure, discoid resection with EEA stapler, and segmental resection. CONCLUSION: Knowledge of different surgical approaches to excise endometriosis is essential to appropriately address a patient's unique pathology. The choice of which surgical technique to use should include consideration of the location of the lesion, depth and circumference of involvement, and the number of nodules present.

Transducin ß-like protein 1 controls multiple oncogenic networks in diffuse large B-cell lymphoma.

Diffuse large B-cell lymphoma (DLBCL) is the most common Non-Hodgkin's lymphoma and is characterized by a remarkable heterogeneity with diverse variants that can be identified histologically and molecularly. Large-scale gene expression profiling studies have identified the germinal center B-cell (GCB-) and activated B-cell (ABC-) subtypes. Standard chemo-immunotherapy remains standard front line therapy, curing approximately two thirds of patients. Patients with refractory disease or those who relapse after salvage treatment have an overall poor prognosis highlighting the need for novel therapeutic strategies. Transducin ß-like protein 1 (TBL1) is an exchange adaptor protein encoded by the TBL1X gene and known to function as a master regulator of the Wnt signalling pathway by binding to ß-CATENIN and promoting its downstream transcriptional program. Here, we show that, unlike normal B-cells, DLBCL cells express abundant levels of TBL1 and its overexpression correlates with poor clinical outcome regardless of DLBCL molecular subtype. Genetic deletion of TBL1 and pharmacological approach using tegavivint, a first-in-class small molecule targeting TBL1 (Iterion Therapeutics), promotes DLBCL cell death in vitro and in vivo. Through an integrated genomic, biochemical, and pharmacologic analyses, we characterized a novel, ß-CATENIN independent, post-transcriptional oncogenic function of TBL1 in DLBCL where TBL1 modulates the stability of key oncogenic proteins such as PLK1, MYC, and the autophagy regulatory protein BECLIN-1 through its interaction with a SKP1-CUL1-F-box (SCF) protein supercomplex. Collectively, our data provide the rationale for targeting TBL1 as a novel therapeutic strategy in DLBCL.

Symmetric benzidine derivatives as anti-HCV agents: Insight into the nature, stereochemistry of the capping amino acid and the size of the terminal capping carbamates.

Novel symmetric molecules, bearing a benzidine prolinamide core, two terminal carbamate caps of variable sizes and nature, including natural and unnatural amino acids were developed. Several terminal N-carbamate substituents of the core structure, ranging from linear methyl, ethyl and butyl groups to branching isobutyl group; and an aromatic substituent were also synthesized. Series 1 has hydrophobic AA residues, namely S and R phenylglycine and a terminal carbamate capping group, whereas Series 2 bears sulphur containing amino acids, specifically S and R methionine and the natural R methylcysteine. The novel compounds were tested for their inhibitory activity (EC50) and their cytotoxicity (CC50), using an HCV 1b (Con1) reporter replicon cell line. Compound 4 with the unnatural capping residue, bearing d-Phenylglycine amino acid residue and N-isobutyloxycarbonyl capping group, was the most active within the two series, with EC50 = 0.0067 nM. Moreover, it showed high SI50 > 14788524 and was not cytotoxic at the highest tested concentration (100 µΜ), indicating its safety profile. Compound 4 also inhibited HCV genotypes 2a, 3a and 4a. Compared to the clinically approved NS5A inhibitor Daclatasvir, compound 4 shows higher activity against genotypes 1b and 3a, as well as improved safety profile.

Adipocytes: A Novel Target for IL-15/IL-15Rα Cancer Gene Therapy.

IL-15 is a proinflammatory cytokine that plays an essential role in the development and activation of natural killer (NK) cells. Adipose tissue acts as an endocrine organ that secretes cytokines and is an important reservoir for lymphocytes. We hypothesized that activation of the IL-15 signaling in adipose tissue will activate and expand the NK cell population and control tumor growth. We recently developed an adipocyte-targeting recombinant adeno-associated viral (rAAV) vector with minimal off-target transgene expression in the liver. Here, we used this rAAV system to deliver an IL-15/IL-15Rα complex to the abdominal fat by intraperitoneal (i.p.) injection. Adipose IL-15/IL-15Rα complex gene transfer led to the expansion of NK cells in the adipose tissue and spleen in normal mice without notable side effects. The i.p. injection of rAAV-IL-15/IL-15Rα complex significantly suppressed the growth of Lewis lung carcinoma implanted subcutaneously and exerted a significant survival advantage in a B16-F10 melanoma metastasis model. The antitumor effects were associated with the expansion of the NK cells in the blood, spleen, abdominal fat, and tumor, as well as the enhancement of NK cell maturity. Our proof-of-concept preclinical studies demonstrate the safety and efficacy of the adipocyte-specific IL-15/IL-15Rα complex vector as a novel cancer immune gene therapy.

IL-18 Drives ILC3 Proliferation and Promotes IL-22 Production via NF-κB.

Group 3 innate lymphoid cells (ILC3s) are important regulators of the immune system, maintaining homeostasis in the presence of commensal bacteria, but activating immune defenses in response to microbial pathogens. ILC3s are a robust source of IL-22, a cytokine critical for stimulating the antimicrobial response. We sought to identify cytokines that can promote proliferation and induce or maintain IL-22 production by ILC3s and determine a molecular mechanism for this process. We identified IL-18 as a cytokine that cooperates with an ILC3 survival factor, IL-15, to induce proliferation of human ILC3s, as well as induce and maintain IL-22 production. To determine a mechanism of action, we examined the NF-κB pathway, which is activated by IL-18 signaling. We found that the NF-κB complex signaling component, p65, binds to the proximal region of the IL22 promoter and promotes transcriptional activity. Finally, we observed that CD11c+ dendritic cells expressing IL-18 are found in close proximity to ILC3s in human tonsils in situ. Therefore, we identify a new mechanism by which human ILC3s proliferate and produce IL-22, and identify NF-κB as a potential therapeutic target to be considered in pathologic states characterized by overproduction of IL-18 and/or IL-22.

Insight into land cover dynamics and water challenges under anthropogenic and climatic changes in the eastern Nile Delta: Inference from remote sensing and GIS data.

The destabilization of delta's worldwide due to climate change and human activities presents challenges in meeting the growing demands for freshwater and food. The Nile Delta in Egypt is a prime example of a vulnerable region facing various stressors. In order to preserve land and water resources, it is crucial to monitor the spatial and temporal changes in Land Use/Land Cover (LULC), shoreline, and Terrestrial Water Storage (TWS) in these vulnerable regions This study comprehensively investigates the dynamic changes in LULC and their associated water and soil responses in the Eastern Nile Delta under these combined impacts. To achieve this goal, a combination of remote sensing techniques utilizing Landsat (5, 8, and 9), and GRACE datasets, along with field observations and Geographic Information System (GIS) tools, was employed. Accordingly, shoreline changes show coastal erosion rates ranging from 5.28 to 34.92 m/year due to climate change-induced SLR, with continued inland movement predicted for the next 20 years. Moreover, the dynamic changes in urbanization and alterations in agricultural cover have considerable penalties for water demand. Analysis of GRACE data indicates a notable reduction in average TWS by 77.89 mm between 2002 and 2017, with an annual rate, estimated at -5.821 mm/year. Soil sampling in highly vulnerable areas confirms agricultural degradation attributed to elevated salinity levels, with EC values ranging from 3.60 to 190 ds/m. These finds provide valuable insights for stakeholders and policymakers, to make reliable strategies regarding water allocation, land use regulations, and climate change adaptation in the worldwide vulnerable deltas.

Beyond the surface: Does stage I-II endometriosis impact fertility? Exploring the challenges of mild disease.

Endometriosis is one of the most common gynecologic conditions that women face throughout their lives. Despite advances in technology, diagnosis and treatment of this relapsing and remitting condition is still challenging for many women. This review focuses on literature pertaining to minimal/mild (stage I/II) endometriosis and its impact on fertility. The effectiveness of medical interventions to improve infertility and obstetric outcomes in both natural and assisted reproductive technologies cycles remains debated. The recent ESHRE guidelines suggests that operative laparoscopy could be considered for rASRM stage I/II endometriosis as it improves ongoing pregnancy rates.

Robotic surgery for deep-infiltrating endometriosis: is it time to take a step forward?

Endometriosis is a chronic debilitating disease that affects nearly 10% of women of the reproductive age. Although the treatment modalities of endometriosis are numerous, surgical excision of the endometriotic implants and nodules remains the sole cytoreductive approach. Laparoscopic excision of endometriosis was proven to be beneficial in improving the postoperative pain and fertility. Moreover, it was also proved to be safe and efficient in treating the visceral localization of deep endometriosis, such as urinary and colorectal endometriosis. More recently, robotic-assisted surgery gained attention in the field of endometriosis surgery. Although the robotic technology provides a 3D vision of the surgical field and 7-degree of freedom motion, the safety, efficacy, and cost-effectiveness of this approach are yet to be determined. With this paper, we aim to review the available evidence regarding the role of robotic surgery in the management of endometriosis along with the current practices in the field.

Surgical Management of Endometriosis Involving the Bladder and Ureter.

BACKGROUND: Endometriosis is a chronic, debilitating condition affecting up to 10% of reproductive-age women. Urinary tract endometriosis is found in 1%-6% of women diagnosed with pelvic endometriosis, with the most common sites being the bladder (70%-85%), ureter (9%-23%), and kidney (4%). Patients typically present with symptoms such as lower abdominal pain, dysuria, and urgency. Unfortunately, urinary tract endometriosis is often asymptomatic, potentially leading to silent obstructive uropathy and kidney failure. OBJECTIVE: To demonstrate a step-by-step approach for the surgical management of urinary tract endometriosis using conventional laparoscopy for partial cystectomy and robotic-assisted laparoscopy for ureteroneocystostomy. MATERIAL AND METHOD: Surgical video of 2 cases managed in an academic tertiary referral center for endometriosis. The first case was a 38-year-old Gravida 3, Para 3 with a history of hysterectomy who had an MRI which revealed a T2 hypointense bladder nodule consistent with endometriosis. Patient had significant urinary urgency, dysuria, and suprapubpic pain that improved but did not disappear after starting oral progestin therapy (5 mg of norethindrone). A cystoscopy was first performed to confirm MRI findings of bladder lesion and to delineate borders and depth of invasion. The second case was a 35-year-old nulliparous woman with chronic pelvic pain and primary infertility. The patient had a history of stage IV endometriosis with deep endometriosis into the bowel and extrinsic encasement of the ureters causing subsequent hydronephrosis requiring bilateral ureteral stents. She had continued daily pelvic pain despite of being on oral contraceptives for medical management of endometriosis. She subsequently underwent bilateral percutaneous nephrostomy tube placement to allow for ureteral rest prior to surgery. RESULTS: In the first case, conventional laparoscopy was utilized to perform bilateral ureterolysis, bladder mobilization, partial cystectomy for complete excision of the lesion, and 2-layered bladder closure. Use of indigo carmine assisted with ureteral orifice identification. In the second case, a cystoscopy was performed with injection of Indocyanine green to assist with ureteral identification. After ureterolysis, distal ureteric obstruction due to extensive disease was confirmed on laparoscopy and ureteroscopy. Bilateral ureteroneocystostomy with placement of Double-J ureteral stents was performed using a robotic-assisted approach. Each patient had an indwelling Foley catheter for bladder decompression during recovery. Pathology in both cases revealed endometriosis. Both patients had an uneventful postoperative course. A postoperative retrograde cystogram confirmed adequate repair prior to removal of each Foley catheter. Patient 2 had uncomplicated office stent removal 6 weeks postoperatively and had a normal renal ultrasound with no hydronephrosis 6 months postoperatively. CONCLUSION: Endometriosis is an increasingly common condition. It is important for gynecological surgeons to have the proper understanding of anatomy, surgical technique, and multidisciplinary care needed with urology for safe and complete excision of bladder and ureter endometriosis.

The Impact of Conservative Surgical Treatment of Adenomyosis on Fertility and Perinatal Outcomes.

Adenomyosis is a benign condition commonly encountered in patients with infertility. While the definitive surgical management is hysterectomy, conservative surgical management is gaining attention in patients desiring future fertility. This review explores whether the surgical treatment of adenomyosis affects fertility outcomes for patients trying to conceive. The PubMed and Medline databases were searched using the keywords: "adenomyosis", "surgery", "radiofrequency", "infertility", "pregnancy", "sterility", "conception", "miscarriage", and "endometrial receptivity". Abstracts were screened, and relevant articles were selected for review. This review reveals that surgery appears to improve fertility outcomes with or without medical therapy; however, the risk of uterine rupture remains high and the best technique to reduce this risk is still not known. More studies are needed to formulate the best surgical approach for preserving fertility in treating adenomyosis and to establish standardized guidelines.

Role of depression in blood pressure control. A cross-sectional multicentric study.

RESEARCH PROBLEM: Hypertension is a multifactorial disease that affects approximately one third of the Tunisian adult population. It is a major risk factor for stroke and cardiovascular disease. Environmental and psychosocial factors play an important role in hypertension onset and control. The prevalence of depression among hypertensive patients is 26, 8% and its presence is associated with increased risk of cardiovascular related morbi-mortality. Our study aims to evaluate the role of depression in blood pressure control among ambulatory hypertensive patients. Investigative process: This study is a cross-sectional, multicentric and descriptive study. We intend to include three hundred and two patients. A 24-hour ambulatory blood pressure monitor will be used to evaluate blood pressure control. Depression will be assessed by the 9-item Patient Health Questionnaire (PHQ-9) in Tunisian dialect. Clinical, socio-environmental, psychosocial and therapeutic and prognosis data will be collected from medical records. Patients will be classified into two groups: Controlled versus non-controlled hypertension. PHQ-9 scores will be then compared between the two cohorts. RESEARCH PLAN: Ethical considerations will be undertaken and respected. All patients should express an informed oral consent before enrollment. This trial will run for three months from the 15th August 2022. TRIAL REGISTRATION: NCT05516173.

COVID-19 is associated with early emergence of preeclampsia: results from a large regional collaborative.

Objective: To investigate the relationship between preeclampsia and SARS-CoV-2 infection during pregnancy. Methods: This was a retrospective cohort study of pregnant women between March and October 2020. Pregnant patients admitted to 14 obstetrical centers in Michigan, USA formed the study population. Of the N = 1458 participants, 369 had SARS-CoV-2 infection (cases). Controls were uninfected pregnancies that were delivered in the same obstetric unit within 30 days of the index case. Robust Poisson regression was used to estimate relative risk (RR) of preterm and term preeclampsia and preeclampsia involving placental lesions. The analysis included adjustment for relevant clinical and demographic risk factors.Results: SARS-CoV-2 infection during pregnancy increased the risk of preeclampsia [adjusted aRR = 1.69 (1.26-2.26)], preeclampsia involving placental lesions [aRR = 1.97(1.14-3.4)] and preterm preeclampsia 2.48(1.48-4.17). Although the highest rate of preeclampsia was observed in patients infected with SARS-CoV-2 who were symptomatic (18.4%), there was increased risk even in asymptomatic SARS-CoV-2 infected patients (14.2%) relative to non-infected controls (8.7%) (p < 0.05). This association with symptomatology was also noted with preterm preeclampsia for which the rate doubled from 2.7% in controls to 5.2% in asymptomatic cases and reached 11.8% among symptomatic cases (p < 0.05). The rate of preterm preeclampsia among cases of pregnant people self-identified as Black reached 10.1% and was almost double the rate of the reminder of the group of infected pregnancies (5.3%), although the rate among uninfected was almost the same (2.7%) for both Black and non-Black groups (interaction p = 0.05).Conclusions: Infection with SARS-CoV-2 increases the risk of preeclampsia even in the absence of symptoms, although symptomatic persons are at even higher risk. Racial disparities in the development of preterm preeclampsia after SARS-CoV-2 infection may explain discrepancies in prematurity between different populations.

Short-term evaluation of autologous transplantation of bone marrow-derived mesenchymal stem cells in patients with cirrhosis: Egyptian study.

BACKGROUND: Stem cell-based therapy has received attention as a possible alternative to organ transplantation. The aim of this study was to assess the safety and efficacy of autologous transplantation of bone marrow (BM)-derived stromal cells in post-HCV liver cirrhosis patients. METHODOLOGY: 10 × 10(6) of isolated human bone marrow (HBM)-stromal cells in 10 mL normal saline were injected in the spleen of 20 patients with end-stage liver cirrhosis guided by the ultrasonography, and then patients were followed up on monthly basis for six months. RESULTS: A statistically significant decrease was detected in the total bilirubin, aspartate transaminase (AST), alanine transaminase (ALT) (p-value<0.01), prothrombin time (PT), and international normalized ratio (INR) levels (p-value<0.05), while a statistically significant increase in the albumin and PC (p-value<0.05) after follow-up. CONCLUSION: This study suggested the safety, feasibility, and efficacy of the intrasplenic injection of autologous BM stromal cells in improving liver function in Egyptian patients with cirrhosis.

Neoadjuvant or adjuvant therapy for resectable gastric cancer: a systematic review and practice guideline for North America.

BACKGROUND: Gastric cancer is a global health problem accounting for 10% of all new cancer cases and 12% of all cancer deaths worldwide. Many clinical trials and meta-analyses have explored the value of neoadjuvant or adjuvant chemotherapy and radiation therapy in gastric cancer; however, these studies have produced conflicting results. The purpose of this guidance document was to determine whether patients with resectable gastric cancer should receive neoadjuvant or adjuvant therapy in addition to surgery. Outcomes of interest were overall survival, disease-free survival, and adverse events. METHODS: A systematic review was undertaken to inform recommendations regarding neoadjuvant and adjuvant therapy in resectable gastric cancer in Ontario, Canada. MEDLINE and EMBASE databases, as well as American Society of Clinical Oncology (ASCO) annual meeting proceedings and American Society for Therapeutic Radiology and Oncology (ASTRO) proceedings were systematically searched from 2002 to 2010. Oral fluoropyrimidine trials were excluded owing to the unavailability of these agents in North America. RESULTS: Overall, 22 randomized controlled trials (RCTs), 13 meta-analyses, and two secondary analyses were included. The systematic review informed the development of a clinical practice guideline with the following recommendations. Postoperative 5-fluorouracil-based chemoradiotherapy based on the Macdonald approach or perioperative ECF (epirubicin, cisplatin, fluorouracil) chemotherapy based on the Cunningham/MAGIC (Medical Research Council Adjuvant Gastric Infusional Chemotherapy) approach are both acceptable standards of care in North America. Choice of treatment should be made on a case-by-case basis. Adjuvant chemotherapy is a reasonable option for those patients for whom the Macdonald and MAGIC protocols are contraindicated. All patients with resectable gastric cancer should undergo a pretreatment multidisciplinary assessment to determine the best plan of care. CONCLUSIONS: Overall survival in patients with resectable gastric cancer is significantly improved with the use of either postoperative chemoradiation (Macdonald approach) or perioperative ECF (MAGIC protocol).

Strategies and factors to maximize cost-effectiveness of robotic surgery in benign gynecological disease.

Operating room procedures account for half of the gross hospital cost in the United States per annum. Hysterectomy is the eighth most common surgery nationally, with more than 300,000 cases every year. Since the introduction of robotic surgery in benign gynecology, concern has been raised regarding the increased cost without significant improvements in outcomes or practice. Surgeon volume, complication rates, length of hospital stay, and selected intraoperative instrumentation are all factors that have a direct effect on cost in robotic surgery. Cost is indirectly influenced by the OR team workflow, postoperative processes to expedite discharge, and converting surgery to the ambulatory setting. More research is needed to develop evidence-based practices for cost containment in robotic surgery.

A step-by-step approach to a frozen pelvis.

OBJECTIVE: To demonstrate a step-by-step approach for restoration of pelvic anatomy in frozen pelvis using a systematic approach to make the steps reproducible, safe, and time efficient. DESIGN: Video presentation. SETTING: Academic medical center. PATIENT(S): A 30-year-old nulliparous woman with lifelong dysmenorrhea and 4 years of infertility who presented for the surgical management of stage IV endometriosis. INTERVENTION(S): An abdominopelvic survey was first in a systematic fashion to assess the extent of adhesive disease and evalaute for normal anatomy. Dissection was then started on the patient's left side to mobilize the sigmoid colon at the pelvic brim. Subsequently, the ureters were identified and bilateral ureterolysis was performed as the retroperitoneal spaces were explored. Once the ureters were safely dissected, the adnexa were mobilized bilaterally. Attention was then turned to the dissection of the medial pararectal spaces (Okabayashi's space) before the dissection of the rectovaginal space. With the restoration of anatomy, the remaining planned surgery was completed. MAIN OUTCOMES MEASURE(S): Restoration of pelvic anatomy, excision of endometriosis, and resolution of symptoms. RESULT(S): The patient had an uncomplicated procedure with complete excision of endometriosis and an estimated blood loss of 45 mL. She was discharged on the same day and had an uneventful postoperative period. At her follow-up appointment, she had resolution of symptoms and was initiated on medical hormone suppression therapy until ready for in vitro fertilization. CONCLUSION(S): A frozen pelvis is a condition in which the pelvic organs are distorted and tethered to each other as a result of adhesive processes. This can obscure normal anatomical landmarks and surgical planes making dissection extremely difficult, thus increasing the risk of interoperative and postoperative complications. Although an uncommon surgical condition, it is not rare to come across in clinical practices, thus creating a challenge to reproductive surgeons as it is commonly seen with endometriosis-associated infertility. It is important for surgeons to be able to recognize the relevant anatomy and have the knowledge to open proper pelvic avascular spaces in the pelvis to mitigate these risks. Following this video's step-by-step approach can help restore pelvic anatomy for planned surgical procedures.