Micronutrient Supplementation and Bone Health After Prophylactic Total Gastrectomy in Patients With CDH1 Variants.

INTRODUCTION: Patients with germline variants in CDH1 who undergo prophylactic total gastrectomy (TG) are at risk of altered nutrient and drug absorption due to modified gastrointestinal anatomy. Bone mineral density loss and micronutrient deficiencies have not been described previously in this patient population. METHODS: In this study we included 94 patients with germline CDH1 variants who underwent prophylactic TG between October 2017 and February 2022. We examined pre- and post-gastrectomy bone mineral density (BMD); serum biomarkers including calcium, phosphorus, alkaline phosphatase, and 25 (OH)-vitamin D; and postoperative adherence to calcium and multivitamin supplementation. RESULTS: Almost all patients (92/94, 98%) lost a substantial amount of weight post-TG, with an average weight loss of 26.5% at 12 months post-surgery. Serum biomarkers of mineral metabolism, namely calcium and phosphorus, did not change significantly after TG. However, average BMD was decreased in all patients at 12 months post-TG. Nonadherence to calcium supplementation was associated with a decrease in BMD. Nonadherence to multivitamin supplementation was associated with greater percent BMD loss in the femoral neck and total hip. CONCLUSIONS: Appropriate micronutrient supplementation and nutritional counseling pre- and postoperatively in patients undergoing prophylactic TG are important to mitigate the long-term effects of gastrectomy on bone health.

Cytoreduction and HIPEC for Gastric Carcinomatosis: Multi-institutional Analysis of Two Phase II Clinical Trials.

INTRODUCTION: There are no approved locoregional therapies for peritoneal carcinomatosis from gastric adenocarcinoma (GA). Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) represents a potential treatment for advanced GA with isolated peritoneal metastasis. PATIENTS AND METHODS: Two separate single-institution phase II, single-arm studies evaluating CRS-HIPEC using cisplatin with mitomycin C (NIH: NCT03092518, MDACC: NCT02891447) in patients with GA and confirmed peritoneal metastasis were analyzed. The primary endpoint of each trial was overall survival (OS). Clinical, pathologic, and treatment variables were analyzed for association with outcomes. RESULTS: Over 4 years, 41 patients with peritoneal carcinomatosis from GA underwent CRS-HIPEC. All patients had synchronous peritoneal metastasis and received systemic chemotherapy as front-line therapy. A total of 23 patients also received laparoscopic HIPEC prior to open CRS-HIPEC. The majority (63%, n = 26) were male, and median PCI score at CRS-HIPEC was 2. Median OS was 24.9 months from diagnosis and 14.4 months from CRS-HIPEC. Three-year OS was 25% from diagnosis and 22% from CRS-HIPEC. Median RFS was 7.4 months. The rate of 30-day Clavien-Dindo grade ≥ 3 complications was 32%; specifically, the rate of anastomotic leak was 22%. Multivariable analysis identified the number of pathologically positive lymph nodes as an independent predictor of postoperative OS. CONCLUSIONS: In patients with gastric adenocarcinoma and isolated peritoneal metastasis treated with CRS-HIPEC, 3-year OS was 22% from CRS-HIPEC, and complications were common. The number of pathologic lymph node metastases was inversely correlated with overall survival. Further investigation of CRS-HIPEC for GA should include patient selection based on response to systemic chemotherapy or incorporate novel intraperitoneal treatment strategies.

International Delphi consensus guidelines for follow-up after prophylactic total gastrectomy: the Life after Prophylactic Total Gastrectomy (LAP-TG) study.

BACKGROUND: Prophylactic total gastrectomy (PTG) remains the only means of preventing gastric cancer for people with genetic mutations predisposing to Hereditary Diffuse Gastric Cancer (HDGC), mainly in the CDH1 gene. The small but growing cohort of people undergoing PTG at a young age are expected to have a life-expectancy close to the general population, however, knowledge of the long-term effects of, and monitoring requirements after, PTG is limited. This study aims to define the standard of care for follow-up after PTG. METHODS: Through a combination of literature review and two-round Delphi consensus of major HDGC/PTG units and physicians, and patient advocates, we produced a set of recommendations for follow-up after PTG. RESULTS: There were 42 first round, and 62 second round, responses from clinicians, allied health professionals and patient advocates. The guidelines include recommendations for timing of assessments and specialties involved in providing follow-up, micronutrient supplementation and monitoring, bone health and the provision of written information. CONCLUSION: While the evidence supporting the guidelines is limited, expert consensus provides a framework to best manage people following PTG, and could support the collection of information on the long-term effects of PTG.

Associations between mindfulness, posttraumatic stress disorder symptoms, and posttraumatic growth in police academy cadets: An exploratory study.

Mindfulness-based treatments have been increasingly noted in the professional literature as a possible means to reduce posttraumatic stress disorder (PTSD) symptoms and promote well-being, especially among law enforcement officers. Scant research, however, has been conducted to study dispositional mindfulness and health outcomes in police cadets. The current exploratory study examined the association between the various facets of dispositional mindfulness (i.e., observing, describing, acting with awareness, nonjudging, and nonreactivity) and PTSD symptoms, posttraumatic growth (PTG), and other variables, including world assumptions, in police cadets (N = 379). Consistent with findings from previous studies of experienced officers, the results indicate that (a) mindful nonjudging is a salient trait in police cadets, which uniquely predicted lower PTSD symptoms, ß = -.31, p < .001, and was related to lower levels of PTG, r = -.12, p = .025, and (b) mindful observing was related to higher levels of PTSD symptoms, r = .14, p = .009 and higher levels of PTG, r = .26, p < .001, in the present sample. In addition, the findings demonstrate that nonjudging is an important trait in police cadets regarding world assumptions such that nonjudging was a significant, unique predictor of world assumption facets, including controllability of events, ß = .15, p = .025, and trustworthiness and goodness of people, ß = .18, p = .004. Clinical implications, including the importance of understanding the association between mindful nonjudging and the shattering and rebuilding of worldviews and following trauma reactions, are discussed.

On the evaluation of edgeless diode detectors for patient-specific QA in high-dose stereotactic radiosurgery.

PURPOSE: In this work, the potential of an innovative "edgeless" silicon diode was evaluated as a response to the still unmet need of a reliable tool for plan dosimetry verification of very high dose, non-coplanar, patient-specific radiosurgery treatments. In order to prove the effectiveness of the proposed technology, we focused on radiosurgical treatments for functional disease like tremor or pain. METHODS: The edgeless diodes response has been validated with respect to clinical practice standard detectors by reproducing the reference dosimetry data adopted for the Treatment Planning System. In order to evaluate the potential for radiosurgery patient-specific treatment plan verification, the anthropomorphic phantom Alderson RANDO has been adopted along with three edgeless sensors, one placed in the centre of the Planning Target Volume, one superiorly and one inferiorly. RESULTS: The reference dosimetry data obtained from the edgeless detectors are within 2.6% for output factor, off-axis ratio and well within 2% for tissue phantom ratio when compared to PTW 60,018 diode. The edgeless detectors measure a dose discrepancy of approximately 3.6% from the mean value calculated by the TPS. Larger discrepancies are obtained in very steep gradient dose regions when the sensors are placed outside the PTV. CONCLUSIONS: The angular independent edgeless diode is proposed as an innovative dosimeter for patient quality assurance of brain functional disorders and other radiosurgery treatments. The comparison of the diode measurements with TPS calculations confirms that edgeless diodes are suitable candidates for patient-specific dosimetric verification in very high dose ranges delivered by non-isocentric stereotactic radiosurgery modalities.

Characteristics of Matriculants to Thoracic Surgery Residency Training Programs.

BACKGROUND: Thoracic surgery (TS) residency positions are in high demand. There is no study describing the nationwide attributes of successful matriculants in this specialty. We examined the characteristics of TS resident applicants and identified factors associated with acceptance. METHODS: Applicant data from 2014 to 2017 application cycles was extracted from the Electronic Residency Application System and stratified by matriculation status. Medical education, type of general surgery residency, and research achievements were analyzed. The number of peer-reviewed publications and the corresponding impact factor for the journals where they were published were quantified. RESULTS: There were 492 applicants and 358 matriculants. The overall population was primarily male (79.5%), white (55.1%), educated at United States allopathic medical schools (66.5%), and trained at university-based general surgery residencies (59.6%). Education at United States allopathic schools (odds ratio [OR], 2.54; P < .0001), being a member of the American Osteopathic Association (OR, 3.27; P = .021), general surgery residency affiliation with a TS residency (OR, 2.41; P = .0003) or National Cancer Institute designated Comprehensive Cancer Center (OR, 1.76; P = .0172), and being a first-time applicant (OR, 4.71, P < .0001) were independently associated with matriculation. Matriculants published a higher number of manuscripts than nonmatriculants (median of 3 vs 2, P < .0001) and more frequently published in higher impact journals (P < .0001). CONCLUSIONS: Our study includes objective and quantifiable data from recent application cycles and represents an in-depth examination of applicants to TS residency. The type of medical school and residency, as well as academic productivity, correlate with successful matriculation.

First experimental measurement of the effect of cardio-synchronous brain motion on the dose distribution during microbeam radiation therapy.

PURPOSE: Microbeam radiation therapy (MRT) is an emerging radiation oncology modality ideal for treating inoperable brain tumors. MRT employs quasi-parallel beams of low-energy x rays produced from modern synchrotrons. A tungsten carbide multislit collimator (MSC) spatially fractionates the broad beam into rectangular beams. In this study, the MSC creates beams 50 µm wide ("peaks") separated by a center-to-center distance of 400 µm ("valleys"). The peak to valley dose ratio (PVDR) is of critical importance to the efficacy of MRT. The underlying radiobiological advantage of MRT relies on high peak dose for tumor control and low valley dose for healthy tissue sparing. Cardio synchronous brain motion of the order 100-200 µm is comparable to microbeam width and spacing. The motion can have a detrimental effect on the PVDR, full width at half maximum (FWHM) of the microbeams, and ultimately the dose distribution. We present the first experimental measurement of the effect of brain motion on MRT dose distribution. Dosimetry in MRT is difficult due to the high dose rate (up to 15-20 kGy/s) and small field sizes. METHODS: A real-time dosimetry system based on a single silicon strip detector (SSSD) has been developed with spatial resolution ~10 µm. The SSSD was placed in a water-equivalent phantom and scanned through the microbeam distribution. A monodirectional positioning stage reproduced brain motion during the acquisition. Microbeam profiles were reconstructed from the SSSD and compared with Geant4 simulation and radiochromic HD-V2 film. RESULTS: The SSSD is able to reconstruct dose profiles within 2 µm compared to film. When brain motion is applied the SSSD shows a two time increase in FWHM of profiles and 50% reduction in PVDR. This is confirmed by Geant4 and film data. CONCLUSIONS: Motion-induced misalignment and distortion of microbeams at treatment delivery will result in a reduced PVDR and increased irradiation of additional healthy tissue compromising the radiobiological effectiveness of MRT. The SSSD was able to reconstruct dose profiles under motion conditions and predict similar effects on FWHM and PVDR as by the simulation. The SSSD is a simple to setup, real-time detector which can provide time-resolved high spatial resolution dosimetry of microbeams in MRT.

Consuming Diet Supplemented with Either Red Wheat Bran or Soy Extract Changes Glucose and Insulin Levels in Female Obese Zucker Rats.

Type 2 diabetes mellitus is characterized by the inability to regulate blood glucose levels due to insulin resistance, resulting in hyperglycemia and hyperinsulinemia. Research has shown that consuming soy and fiber may protect against type 2 diabetes mellitus. We performed a study to determine whether supplementing diet with soy extract (0.5% weight of diet) or fiber (as red wheat bran; 11.4% weight of diet) would decrease serum insulin and blood glucose levels in a pre-diabetic/metabolic syndrome animal model. In our study, female obese Zucker rats were fed either a control diet (n = 8) or control diet supplemented with either soy extract (n = 7) or red wheat bran (n = 8) for seven weeks. Compared to rats consuming control diet, rats fed treatment diets had significantly lower (p-value < 0.05) fasting serum insulin (control = 19.34±1.6; soy extract = 11.1±1.54; red wheat bran = 12.4±1.11) and homeostatic model assessment of insulin resistance values (control = 2.16±0.22; soy extract = 1.22±0.21; red wheat bran = 1.54±0.16). Non-fasted blood glucose was also significantly lower (p-value < 0.05) in rats fed treatment diets compared to rats consuming control diet at weeks four (control = 102.63±5.67; soy extract = 80.14±2.13; red wheat bran = 82.63±3.16), six (control = 129.5±10.83; soy extract = 89.14±2.48; red wheat bran = 98.13±3.54), and seven (control = 122.25±8.95; soy extract = 89.14±4.52; red wheat bran = 84.75±4.15). Daily intake of soy extract and red wheat bran may protect against type 2 diabetes mellitus by maintaining normal glucose homeostasis.

A Phase II Trial of Cytoreduction and Hyperthermic Intraperitoneal Chemotherapy for Recurrent Adrenocortical Carcinoma.

BACKGROUND: Recurrent adrenocortical carcinoma (ACC) is an aggressive disease with few options offering durable survival benefit. Despite metastasectomy, recurrence is common. Cytoreduction and intraperitoneal chemotherapy have offered improved survival in other advanced cancers. We sought to evaluate the use of cytoreduction and hyperthermic intraperitoneal chemotherapy (HIPEC) for the treatment of recurrent intraperitoneal ACC. METHODS: A phase II, single institution clinical trial was approved for patients with radiographic evidence of resectable ACC limited to the peritoneum. Patients underwent treatment if optimal cytoreduction was deemed possible at exploratory laparotomy. Primary outcome was intraperitoneal progression-free survival. Secondary outcomes were treatment-related morbidities and overall survival. RESULTS: Sixty-three patients were evaluated, of whom 11 met eligibility criteria. Nine patients underwent cytoreduction and HIPEC, including one patient who recurred and was re-treated (n = 10 treatments). One patient could not be optimally cytoreduced for HIPEC and therefore did not receive intraperitoneal chemotherapy. There was no perioperative mortality; perioperative comorbidities were limited to Clavien-Dindo grade 2 or 3 and included hematologic, infectious, and neurologic complications. Seven patients experienced disease recurrence and two patients died of disease during follow-up (median 24 mo). Intraperitoneal progression-free survival was 19 mo, and median overall survival has not yet been reached. CONCLUSIONS: Cytoreduction and HIPEC can be performed safely in selected patients. Patients with recurrent ACC confined to the peritoneal cavity can be considered for regional therapy in experienced hands. However, disease recurrence is common, and other treatment options should be explored.

An Examination of Applicants and Factors Associated with Matriculation to Complex General Surgical Oncology Fellowship Training Programs.

BACKGROUND: The demand for training in complex general surgical oncology (CGSO) fellowships currently exceeds the number of positions offered; however, there are scarce data defining the applicant pool or characteristics associated with successful matriculation. Our study described the applicant population and to determine factors associated with acceptance into the fellowship. STUDY DESIGN: Data were extracted from the Electronic Residency Application System for applicants in 2015 and 2016 and stratified based on matriculation status. Applicant demographics, including medical education, residency, and research achievements, were analyzed. Academic productivity was quantified using the number of peer-reviewed publications as well as the journal with the highest impact factor in which an applicant's work was published. RESULTS: Data were gathered on a total of 283 applicants, of which 105 matriculated. The overall population was primarily male (63.2%), Caucasian (40.6%), educated at a U.S. allopathic medical school (53.4%), and trained at a university-based General Surgery residency (55.5%). Education at a U.S. allopathic school (OR = 5.63, p < 0.0001), university-based classification of the applicant's surgical residency (OR = 4.20, p < 0.0001), and a residency affiliation with a CGSO fellowship (OR = 2.61, p = 0.004) or National Cancer Institute designated Comprehensive Cancer Center (OR = 3.16, p < 0.001) were found to be associated with matriculation. Matriculants published a higher number of manuscripts than nonmatriculants (median of 10 vs. 4.5, p < 0.0001) and more frequently achieved publication in journals with higher impact factors (p < 0.0001). CONCLUSIONS: This study represents the first objective description of the CGSO fellowship applicant pool. Applicants' medical school, residency, and research data points correlated with successful matriculation.

Transcriptional Regulation of TCF/LEF and PPARγ by Daidzein and Genistein in 3T3-L1 Preadipocytes.

Adipogenesis is central to adipose tissue plasticity and lipid homeostasis. Regulation of adipogenic signaling by phytoestrogens has been implicated as a potential therapeutic strategy for obesity-related disease. However, it remains unclear how these compounds directly impact transcriptional control of adipogenesis. As such, the focus of this study was to determine how daidzein and genistein effect transcriptional activation of peroxisome proliferator-activated receptor gamma (PPARγ) and TCF/LEF in 3T3-L1 preadipocytes. We also measured the effect of estrogen receptor (ER) knockdown on expression of preadipocyte (i.e., Pref1) and adipocyte (i.e., Fabp4) markers in cells treated with varying concentrations of daidzein or genistein (i.e., 10-4, 10-7, and 10-10). Our findings showed that activation of TCF/LEF was induced by daidzein and genistein in undifferentiated and differentiated 3T3-L1 preadipocytes. Conversely, PPARγ reporter activity was inhibited by genistein, which corresponded with a reduction in cell diameter of differentiated preadipocytes. Daidzein increased cell diameter, as well as reduced Pref1 abundance in undifferentiated cells. Although small, there was a significant reduction in Pref1 and Fabp4 abundance in undifferentiated cells with ERα and ERß knockdown. However, reduced abundance of ER subtypes exhibited no significant effect on phytoestrogen treatment. Collectively, our findings show phytoestrogens distinctly regulate adipogenic transcription factors and thus, may have implications for adipose dysfunction and obesity-related disease.

Assessing the outcomes, risks, and costs of local versus general anesthesia: A review with implications for cutaneous surgery.

BACKGROUND: There is a paucity of data providing direct comparison of outcomes, complications, and costs between general and local anesthesia in cutaneous surgery. OBJECTIVE: Analyze the literature from dermatologic and other specialties to compare outcomes, risks, and costs of general and local anesthesia. METHODS: A retrospective analysis of case comparison studies from other specialties comparing outcomes, risks, and/or costs in local versus general anesthesia was performed. A review of the literature from dermatology and other specialties was included. RESULTS: A total of 51 studies were selected; 41 of them directly examined outcomes in procedures performed under local and general anesthesia, and none found a significant difference in outcomes. A total of 41 studies measured adverse effects. Of these, 15 studies (36.6%) report significantly better outcomes between the 2 techniques. Only 2 studies (4.9%) report significantly improved outcomes with use of general anesthesia; 15 of 36 studies (41.7%) report fewer adverse events in local anesthesia. Of the 13 studies that examined costs, all (100%) found significantly decreased costs with use of local anesthesia. LIMITATIONS: These data cannot be seamlessly applied to all cases of cutaneous surgery. CONCLUSION: Local anesthesia techniques provide outcomes equal to or better than general anesthesia and with significantly lower costs.

Postgastrectomy Syndromes and Nutritional Considerations Following Gastric Surgery.

Postgastrectomy syndromes result from altered form and function of the stomach. Gastrectomy disrupts reservoir capacity, mechanical digestion and gastric emptying. Early recognition of symptoms with prompt evaluation and treatment is essential. Many syndromes resolve with minimal intervention or dietary modifications. Re-operation is not common but often warranted for afferent and efferent loop syndromes and bile reflux gastritis. Preoperative nutritional assessment and treatment of common vitamin and mineral deficiencies after gastrectomy can reduce the incidence of chronic complications. An integrated team approach to risk assessment, patient education, and postoperative management is critical to optimal care of patients with gastric cancer.

Effect of stearidonic acid-enriched soybean oil on fatty acid profile and metabolic parameters in lean and obese Zucker rats.

BACKGROUND: Consumption of marine-based oils high in omega-3 polyunsaturated fatty acids (n3PUFAs), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) is known to protect against obesity-related pathologies. It is less clear whether traditional vegetable oils with high omega-6 polyunsaturated fatty acid (n6PUFA) content exhibit similar therapeutic benefits. As such, this study examined the metabolic effects of a plant-based n3PUFA, stearidonic acid (SDA), in polygenic obese rodents. METHODS: Lean (LZR) and obese Zucker (OZR) rats were provided either a standard westernized control diet (CON) with a high n6PUFA to n3PUFA ratio (i.e., 16.2/1.0) or experimental diet modified with flaxseed (FLAX), menhaden (FISH), or SDA oil that resulted in n6PUFA to n3PUFA ratios of 1.7/1.0, 1.3/1.0, and 1.0/0.8, respectively. RESULTS: After 12 weeks, total adiposity, dyslipidemia, glucose intolerance, and hepatic steatosis were all greater, whereas n3PUFA content in liver, adipose, and muscle was lower in OZR vs. LZR rats. Obese rodents fed modified FISH or SDA diets had lower serum lipids and hepatic fat content vs. CON. The omega-3 index (i.e., ΣEPA + DHA in erythrocyte membrane) was 4.0, 2.4, and 2.0-fold greater in rodents provided FISH, SDA, and FLAX vs. CON diet, irrespective of genotype. Total hepatic n3PUFA and DHA was highest in rats fed FISH, whereas both hepatic and extra-hepatic EPA was higher with FISH and SDA groups. CONCLUSIONS: These data indicate that SDA oil represents a viable plant-derived source of n3PUFA, which has therapeutic implications for several obesity-related pathologies.

Stearidonic acid: is there a role in the prevention and management of type 2 diabetes mellitus?

Obesity and its related comorbidities are major public health concerns in the United States with over two-thirds of adults and one-third of children classified as overweight or obese. The prevalence of type 2 diabetes mellitus (T2DM) has similarly risen to an estimated 25.8 million, which accounts for a staggering $174 billion in annual healthcare costs. Identification of dietary interventions that protect against the development of T2DM would markedly reduce the medical and economic consequences of the disease. Hence, we review current evidence supporting a role of (n-3) PUFA in T2DM and explore potential therapeutic implications of stearidonic acid (SDA). The low consumption of fish in the US along with a reduced efficiency to interconvert most plant (n-3) PUFA highlights a need to find alternative sources of (n-3) PUFA. The efficient biological conversion of SDA to EPA underscores the potential implications of SDA as a source of (n-3) PUFA. The full therapeutic efficacy of SDA remains to be further determined. However, recent data have suggested a protective role of SDA consumption on markers of dyslipidemia and inflammation. The AHA recommends that healthy individuals consume oily fish at least twice per week and individuals with a history of cardiovascular disease consume 1 g of EPA+DHA/d. These goals will likely not be met by the typical American diet. Therefore, SDA may represent a sustainable alternative to marine-based (n-3) PUFA and may have novel therapeutic efficacy regarding the development of T2DM.

Prospective randomized trial evaluating mandatory second look surgery with HIPEC and CRS vs. standard of care in patients at high risk of developing colorectal peritoneal metastases.

BACKGROUND: The standard of care for colorectal peritoneal carcinomatosis is evolving from chemotherapy to cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) for patients with disease limited to the peritoneum. Peritoneal carcinomatosis from colorectal cancer treated with chemotherapy alone results in median survival of 5 to 13 months, whereas CRS with HIPEC for early peritoneal carcinomatosis from colorectal cancer resulted in median survival of 48-63 months and 5 year survival of 51%.Completeness of cytoreduction and limited disease are associated with longer survival, yet early peritoneal carcinomatosis is undetectable by conventional imaging. Exploratory laparotomy can successfully identify early disease, but this approach can only be justified in patients with high risk of peritoneal carcinomatosis. Historical data indicates that patients presenting with synchronous peritoneal carcinomatosis, ovarian metastases, perforated primary tumor, and emergency presentation with bleeding or obstructing lesions are at high risk of peritoneal carcinomatosis. Approximately 55% of these patient populations will develop peritoneal carcinomatosis. We hypothesize that performing a mandatory second look laparotomy with CRS and HIPEC for patients who are at high risk for developing peritoneal carcinomatosis from colorectal cancer will lead to improved survival as compared to patients who receive standard of care with routine surveillance. METHODS/DESIGN: This study is a prospective randomized trial designed to answer the question whether mandatory second look surgery with CRS and HIPEC will prolong overall survival compared to the standard of care in patients who are at high risk for developing peritoneal carcinomatosis from colorectal cancer (CRC). Patients with CRC at high risk for developing peritoneal carcinomatosis who underwent curative surgery and subsequently received standard of care adjuvant chemotherapy will be evaluated. The patients who remain without evidence of disease by imaging, physical examination, and tumor markers for 12 months after the primary operation will be randomized to mandatory second look surgery or standard-of-care surveillance. At laparotomy, CRS and HIPEC will be performed with intraperitoneal oxaliplatin with concurrent systemic 5-fluorouracil and leucovorin. Up to 100 patients will be enrolled to allow for 35 evaluable patients in each arm; accrual is expected to last 5 years. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT01095523.

Novel nucleotide triphosphates as potent P2Y2 agonists.

The synthesis and P2Y2 activities of a novel series of nucleoside triphosphates are described. Many of these compounds were potent agonists of the P2Y2 receptor.