A case of distal extrahepatic cholangiocarcinoma with two positive resection margins

Cholangiocarcinoma is an uncommon primary malignancy of the biliary tract that is challenging to diagnose and treat effectively due to its relatively silent and late clinical presentation. The present study reports a case of a 60-year-old male with distal extrahepatic cholangiocarcinoma with a 3-week history of painless obstructive jaundice symptoms and subjective weight loss. Imaging revealed an obstructing lesion in the common bile duct, just distal to the entrance of the cystic duct. Pathology revealed moderately differentiated cholangiocarcinoma with two positive proximal resection margins. The two positive resection margins presented a challenge during surgery and points to an urgent need for further studies to better illuminate diagnostic and therapeutic options for patients with similar clinicopathological presentation

Commissioning report of the MuCool 5 Tesla solenoid coupled with helium refrigerator

MuCool 5T solenoid was successfully cooled down and operated coupled with MTA 'Brown' refrigerator. The system performed as designed with substantial performance margin. All process alarms and interlocks, as well as ODH and fire alarms, were active and performed as designed. The cooldown of the refrigerator started from warm conditions and took 44 hours to accumulate liquid helium level and solenoid temperature below 5K. Average liquid nitrogen consumption for the refrigerator precool and solenoid shield was measured as 20 gal/hr (including boil-off). Helium losses were small (below 30 scfh). The system was stable and with sufficient margin of performance and ran stably without wet expansion engine. Quench response demonstrated proper operation of the relieving devices and pointed to necessity of improving tightness of the relieving manifolds. Boil-off test demonstrated average heat load of 3 Watts for the unpowered solenoid. The solenoid can stay up to 48 hours cold and minimally filled if the nitrogen shield is maintained. A list of improvements includes commencing into operations the second helium compressor and completion of improvements and tune-ups for system efficiency

A Proposal for a Three Detector Short-Baseline Neutrino Oscillation Program in the Fermilab Booster Neutrino Beam

A Short-Baseline Neutrino (SBN) physics program of three LAr-TPC detectors located along the Booster Neutrino Beam (BNB) at Fermilab is presented. This new SBN Program will deliver a rich and compelling physics opportunity, including the ability to resolve a class of experimental anomalies in neutrino physics and to perform the most sensitive search to date for sterile neutrinos at the eV mass-scale through both appearance and disappearance oscillation channels. Using data sets of 6.6e20 protons on target (P.O.T.) in the LAr1-ND and ICARUS T600 detectors plus 13.2e20 P.O.T. in the MicroBooNE detector, we estimate that a search for muon neutrino to electron neutrino appearance can be performed with ~5 sigma sensitivity for the LSND allowed (99% C.L.) parameter region. In this proposal for the SBN Program, we describe the physics analysis, the conceptual design of the LAr1-ND detector, the design and refurbishment of the T600 detector, the necessary infrastructure required to execute the program, and a possible reconfiguration of the BNB target and horn system to improve its performance for oscillation searches.Comment: 209 pages, 129 figure

Surgical Updates in the Treatment of Pelvic Organ Prolapse

Pelvic organ prolapse affects approximately 8% of women, and the demand for pelvic organ prolapse surgery is expected to increase by nearly 50% over the next 40 years. The surgical techniques used to correct pelvic organ prolapse have evolved over the last 10 years, with multiple well-designed studies addressing the risks, outcomes, reoperation rates, and optimal surgical approaches. Here we review the most recent evidence on the route of access, concomitant procedures, and synthetic materials for augmenting the repair. Ultimately, this review highlights that there is no optimal method for correcting pelvic organ prolapse and that the risks, benefits, and approaches should be discussed in a patient-centered, goal-oriented approach to decision-making

Operations aspects of the Fermilab Central Helium Liquefier Facility

The Fermilab Central Helium Liquefier (CHL) facility consists of helium and nitrogen reliquefier plants operated 24 hours-a-day to supply LHe at 4.6{degrees}K and LN{sub 2} for the Fermilab Tevatron superconducting proton-antiproton collider ring and to recover warm return gases. Operating aspects of CHL, including different equipment and systems reliability, availability, maintenance experience, safety concerns, and economics aspects are discussed

Operations aspects of the Fermilab Central Helium Liquefier facility

The Fermilab Central Helium Liquefier (CHL) facility consists of helium and nitrogen reliquefier plants operated 24 hours-a-day to supply LHe at 4.6 K and LN{sub 2} for the Fermilab Tevatron superconducting proton-antiproton collider ring and to recover warm return gases. Operating aspects of CHL, including different equipment and systems reliability, availability, maintenance experience, safety concerns, and economics aspects are discussed

Temporal Trends in Grade 3/4 Adverse Events and Associated Costs of Nivolumab Plus Cabozantinib Versus Sunitinib for Previously Untreated Advanced Renal Cell Carcinoma

Advanced Renal Cell Carcinoma; Adverse Events; NivolumabCarcinoma de células renales avanzado; Eventos adversos; NivolumabCarcinoma de cèl·lules renals avançat; Esdeveniments adversos; NivolumabBackground and Objectives Novel immunotherapy-based combination treatments have drastically improved clinical outcomes for previously untreated patients with advanced/metastatic renal cell carcinoma (aRCC). This study aimed to assess the temporal trends in grade 3/4 adverse event (AE) rates and associated costs of nivolumab plus cabozantinib combination therapy versus sunitinib monotherapy in previously untreated patients with aRCC. Methods Individual patient data from the CheckMate 9ER trial (nivolumab plus cabozantinib: N = 320; sunitinib: N = 320) were used to calculate the proportion of patients experiencing grade 3/4 AEs. AE unit costs were obtained from the United States (US) 2017 Healthcare Cost and Utilization Project (HCUP) and inflated to 2020 US dollars. Per-patient-per-month (PPPM) all-cause and treatment-related grade 3/4 AE costs over 18-months, temporal trends, and top drivers of AE costs were evaluated in both treatment arms. Results Overall, the proportion of patients experiencing grade 3/4 AEs decreased over time, with the highest rates observed in the first 3 months for the nivolumab plus cabozantinib and sunitinib arms. Compared with sunitinib, nivolumab plus cabozantinib was associated with consistently lower average all-cause AE costs PPPM [month 3: $2021 vs.$3097 (p 0.05); month 18: $1337 vs.$1755 (p > 0.05)]. Over 18 months, metabolism and nutrition disorders ($244), laboratory abnormalities ($182), and general disorders and administration site conditions ($122) were the costliest all-cause PPPM AE categories in the nivolumab plus cabozantinib arm, and laboratory abnormalities ($443), blood and lymphatic system disorders ($254), and metabolism and nutrition disorders ($177) were the costliest in the sunitinib arm. Trends of treatment-related AE costs were consistent with all-cause AE costs. Conclusions Nivolumab plus cabozantinib was associated with lower costs of grade 3/4 AE management PPPM than sunitinib, which accumulated over the 18-month study period

Grade 3/4 Adverse Event Costs of Immuno-oncology Combination Therapies for Previously Untreated Advanced Renal Cell Carcinoma

Advanced renal cell carcinoma; Adverse event cost; Nivolumab plus cabozantinibCarcinoma de células renales avanzado; Coste de eventos adversos; Nivolumab más cabozantinibCarcinoma de cèl·lules renals avançat; Cost d'esdeveniments adversos; Nivolumab més cabozantinibBackground Despite 4 approved combination regimens in the first-line setting for advanced renal cell carcinoma (aRCC), adverse event (AE) costs data are lacking. Materials and Methods A descriptive analysis on 2 AE cost comparisons was conducted using patient-level data for the nivolumab-based therapies and published data for the pembrolizumab-based therapies. First, grade 3/4 AE costs were compared between nivolumab + ipilimumab vs. nivolumab + cabozantinib vs. pembrolizumab + axitinib using data from the CheckMate 214 (median follow-up [mFU]: 13.1 months), CheckMate 9ER (mFU: 12.8 months), and KEYNOTE-426 (mFU: 12.8 months) trials, respectively. Second, grade 3/4 AE costs were compared between nivolumab + ipilimumab vs. nivolumab + cabozantinib vs. pembrolizumab + lenvatinib using data from the CheckMate 214 (mFU: 26.7 months), CheckMate 9ER (mFU: 23.5 months), and KEYNOTE-581 (mFU: 26.6 months) trials, respectively. Per-patient costs for all-cause and treatment-related grade 3/4 AEs with corresponding any-grade AE rates ≥ 20% were calculated based on the Healthcare Cost and Utilization Project database and inflated to 2020 US dollars. Results Per-patient all-cause grade 3/4 AE costs for nivolumab + ipilimumab vs. nivolumab + cabozantinib vs. pembrolizumab + axitinib were $2703 vs.$4508 vs. $5772, and treatment-related grade 3/4 AE costs were$741 vs. $2722 vs.$4440 over ~12.8 months of FU. For nivolumab + ipilimumab vs. nivolumab + cabozantinib vs. pembrolizumab + lenvatinib, per-patient all-cause grade 3/4 AE costs were $3120 vs.$5800 vs. $9285, while treatment-related grade 3/4 AE costs were$863 vs. $3162 vs.$5030 over ~26.6 months of FU. Conclusion Patients with aRCC treated with first-line nivolumab-based therapies had lower grade 3/4 all-cause and treatment-related AE costs than pembrolizumab-based therapies, suggesting a more favorable cost-benefit profile.This study was funded by Bristol Myers Squibb

Determining Front-Line Therapeutic Strategy for Metastatic Clear Cell Renal Cell Carcinoma

The therapeutic landscape for metastatic renal cell carcinoma has rapidly evolved over the years, and we are now in an era of combination therapy strategies employing immune checkpoint blockade and anti-angiogenesis targeted therapy. Since 2018, we have gained regulatory approval for four distinct combination therapies, all with survival benefits, and with guideline recommendation for use in the front-line setting. As such, treatment selection has become increasingly complex with a myriad of treatment choices but little high-level head-to-head data to guide treatment selection. Heterogeneity in tumor biology further complicates treatment selection as tumors vary in behavior and treatment responsiveness. Ongoing development of biomarkers will certainly assist in this setting, and validation of predictive markers represents an unmet need. In their absence, we highlight features of disease and nuances to datasets from landmark prospective clinical trials to help inform treatment selection. There is growing evidence to support deferring upfront systemic therapy in some patients, with opportunities for active surveillance or metastasis-directed therapy. In others, upfront systemic therapy is warranted and necessitates thoughtful consideration of multiple clinicopathologic parameters to inform optimal patient-centered decision making