bluuebunny/crossref_metadata_2025_split huggingface dataset:
Natural history study and tissue procurement of neuroendocrine neoplasms (NENs).
Authors: Mallorson Rosa , Cortez Briana N. , Varghese Diana Grace , Naimian Amirkia , Magee Tamika , Kelley Sarah , Kumar Suresh , Roper Nitin , Pommier Yves , Del Rivero Jaydira 
Published: January 2023

TPS659 Background: Neuroendocrine neoplasms (NENs) are a rare spectrum of malignant neoplasms originating from neuroendocrine cells, most commonly affecting the gastrointestinal tract, pancreas, and lungs. Tumors may vary from low grade neuroendocrine tumors (NET) to high grade neuroendocrine carcinomas (NEC). The annual occurrence of NENs is increasing worldwide and currently the incidence in the US is about 6 cases per 100,000 people per year. A variety of therapeutic options are available for advanced NENs, however, when to apply a given option, what combination therapeutic approach should be used, how long treatment should be continued is unclear and controversial. Moreover, unlike common cancers, pre-clinical models for NENs are sorely limited. Without robust pre-clinical models our understanding of tumor pathophysiology and novel drug development can be challenging. Methods: A prospective study to evaluate the natural history and sample acquisition of NENs comprehensively and longitudinally. Patients ≥ 18 years old with histological confirmation of NENs, biochemical evidence of NENs, or by imaging studies of NENs are eligible. Participants are invited to NIH for biannual evaluations or as clinically indicated. Patients complete individual medical history, family history, and laboratory assessments including blood, saliva, and tumor for RNA/DNA analysis. A tumor analysis via a 500+ gene panel (Illumina TruSight Oncology 500 Panel) is performed for comprehensive genomic and epigenomic analysis. When feasible, fresh tissue is collected to develop pre-clinical models for drug testing. If clinically indicated, anatomic and functional imaging is performed. We aim to 1) create a repository of biological samples and conduct future investigations to understand the basic biology of NENs with the goal to develop novel treatment approaches, biomarkers of treatment response, and new prognostic and diagnostic models, 2) acquire clinical data so that the overall genomic, proteomic, and metabolomic alternations can be correlated to clinical parameters, 3) establish organoid cultures, cell line models, and xenograft models corresponding to NENs of various grades for drug screening. This protocol will evaluate the natural history of NENs, allow tissue acquisition, and study this heterogenous group of neoplasms with unique tumor biology, and current clinical management to stabilize correlations with clinical outcomes and develop novel therapies. Clinical trial information: NCT05237934 .
APOLLO: A randomized phase II double-blind study of olaparib versus placebo following curative intent therapy in patients with resected pancreatic cancer and a pathogenic BRCA1, BRCA2 or PALB2 mutation—ECOG-ACRIN EA2192.
Authors: Reiss Kim Anna , Hong Sung Chul , Kasi Anup , O'Reilly Eileen Mary , Maithel Shishir K. , Yao Xin , Hamilton Stanley R. , Boursi Ben , Pishvaian Michael J. , Klempner Samuel J , Domchek Susan M. , Catalano Paul J. , Chiorean E. Gabriela , Philip Philip Agop , O'Dwyer Peter J. 
Published: January 2023

TPS763 Background: A meaningful subset of PDAC is characterized by a homologous recombination deficiency (HRD). The most well-defined patients within this group are those with pathogenic variants in BRCA1, BRCA2 and PALB2. In the metastatic setting, PARP inhibitor maintenance provides a progression-free survival benefit after a period of platinum based chemotherapy1,2, but the role of PARP inhibitors in the curative intent setting is undefined. The OlympiA study established one year of olaparib as the standard of care for patients with BRCA-related, early stage breast cancer who completed all other curative-intent treatment3. Therefore, we have designed a randomized, phase II double-blind study of one year of olaparib vs placebo in patients with pancreatic cancer and a germline or somatic variant in BRCA or PALB2 who have completed all curative intent therapy. Methods: We have enrolled and treated 23 of 152 planned patients on study NCT 04858334/EA2192. Eligibility criteria include: a pathogenic germline or somatic variant in BRCA1, BRCA2 or PALB2 as determined by local laboratory (central review required); completion of curative-intent resection and ≥ three months of multi-agent chemotherapy; no evidence of recurrent disease. At enrollment, patients must be within 12 weeks of their last anti-cancer intervention. Patients are randomized 2:1 to receive oral olaparib 300 mg twice daily or placebo for 12 28-day cycles. The primary endpoint is relapse-free survival. Overall survival is a secondary endpoint. Tumor tissue, fecal material (for microbiome analysis) and serial ctDNA samples are being collected. 1.Golan T, Locker GY, Kindler HL: N Engl J Med 381:1492-1493, 2019. 2. Reiss KA, Mick R, O'Hara MH, et al: J Clin Oncol 39:2497-2505, 2021. 3. Tutt ANJ, Garber JE, Geyer CE, Jr.: N Engl J Med 385:1440, 2021. Clinical trial information: NCT04858334 .
A phase I dose escalation study of carbon-ion radiotherapy for pancreatic cancer.
Authors: Shinoto Makoto , Takiyama Hirotoshi , Isozaki Tetusro , Yamada Shigeru 
Published: January 2023

TPS768 Background: Despite recent advances in chemotherapy and radiotherapy, the prognosis of unresectable locally pancreatic cancer (LAPC) patients remains poor. To improve the outcome, we have developed carbon ion radiotherapy (C-ion RT) for pancreatic cancer and have shown good results against conventional photon therapy. Compared to conventional photon therapy, C-ion RT can safely administer higher doses, and we find the possibility of long-term survival for some unresectable LAPC. Currently, C-ion RT is performed using 55.2 Gy (RBE) in 12 fractions. However local control is not satisfactory. Further dose escalation needs to be safely administered to further improve outcomes. We have developed a new treatment strategy: intensity-modulated ion therapy using the simultaneous integrated boost method and the linear transfer energy (LET) optimization method. We believe that these cutting-edge technologies will allow for a more intensive effect on pancreatic cancer. Thus, we started a clinical trial to evaluate the safety of dose escalation using these novel techniques. Methods: Eligibility included pathological or clinical confirmation of pancreatic cancer without distant metastasis. Carbon ion radiotherapy is given in 12 fractions over 3 weeks. The radiation doses are set in four steps, with increases ranging from 55.2 Gy (RBE) to 67.2 Gy (RBE). A minimum of three patients is enrolled in each cohort, and if there is no dose limiting toxicity (DLT), a dose escalation is performed. The primary endpoint is acute adverse events; the secondary outcomes are late adverse events, local control rate, and overall survival. We started this trial in September 2021. Cohort 1 has been completed without DLT. Cohort 2 is now starting enrollment. Clinical trial information: jRCTs032210292 .
Casper: A phase I, open-label, dose finding study of calaspargase pegol-mnkl (cala) in combination with cobimetinib (cobi) in locally advanced or metastatic pancreatic ductal adenocarcinoma (PDAC).
Authors: Lopez Charles D. , Kardosh Adel , Chen Emerson Yu-sheng , Pegna Guillaume Joe , Goodyear Shaun , Taber Erin , Rajagopalan Brindha , Edmerson Exodus , Vo Johnson , Jackson Anna , Gingerich Tasha , Fahlman Anne , Ventura Diane , Roy Preeyam , Keith Dove , Mills Gordon B. , Brody Jonathan , Sheppard Brett C. , Sears Rosalie C. , Ronai Ze'ev 
Published: January 2023

TPS772 Background: Metabolic adaptation provides rapidly dividing cancer cells the flexibility to maintain homeostasis as nutrient supplies are continuously exhausted in the tumor microenvironment. Asparagine synthetase (ASNS) catalyzes ATP-dependent biosynthesis of the non-essential amino acid asparagine from aspartate and glutamine. Cells lacking ASNS, however, are auxotrophic for asparagine. Use of L-asparaginase (ASNase) to promote asparagine starvation in PDAC and other solid tumors with low ASNS levels is a rationale treatment strategy; however, aberrant RAS/MAPK signaling can circumvent effects of ASNase. Preclinical data shows that targeted inhibition of MAPK signaling along with ASNase is active against PDAC; however, this has not been tested in patients to date. Methods: CASPER is an open-label, phase IB, single-arm, dose-escalation study to evaluate the safety and tolerability of combining cala and cobi in patients with locally-advanced or metastatic PDAC. Participants receive cala and cobi at assigned dose level. The study uses a Bayesian Optimal Interval (BOIN) design to determine the maximum tolerated dose (MTD) for the combination of study agents. Up to 15 participants will be enrolled and treated, with a cohort of 3 participants assessed before a decision is made to escalate, de-escalate, or maintain the current dose level before initiating the next cohort. MTD is defined as the dose level where dose-limiting toxicity (DLT) probability is closest to the target toxicity rate of 30% after applying isotonic regression to the observed dose-level-specific DLT rate. Per BOIN, the dose level is escalated, maintained, or de-escalated based on comparisons of the observed DLT rate and pre-specified boundaries (0.236, 0.359). Starting in Cycle (C) 1, patients receive cobi (at assigned dose level) for Days (D) 1-14, and their assigned dose of cala on D1 of each 21-day cycle. If the combination of cala and cobi is tolerated and does not incur DLTs, participants will continue receiving their assigned dose of cala and cobi until evidence of disease progression, unacceptable toxicity, or study withdrawal. The DLT period starts on C1D1 and ends C2D21. Secondary endpoints include preliminary assessment of overall response rate (ORR), disease control rate (DCR), and mean levels of plasma ASNase. Paired tumor biopsies and serial blood will be used for exploratory objectives combining deep multi-omic analytics with clinical data. The trial is currently open with 1 patient enrolled at time of submission. Clinical trial information: NCT05034627 . [Table: see text]
The SHARON trial: A study of melphalan, BCNU, hydroxocobalamin, ascorbic acid, and autologous stem cell rescue for metastatic pancreatic cancer with an inherited BRCA mutation.
Authors: Yu Kenneth H. , Weekes Colin D. , Chen Yi-Bin Albert , Glazier Jeffrey Aaron , Glazier Arnold , Dahi Parastoo , Giralt Sergio , O'Reilly Eileen Mary 
Published: January 2023

TPS774 Background: SHARON is a phase 1, single-arm trial to assess the safety and preliminary efficacy of 2 cycles of melphalan, BCNU, hydroxocobalamin (vitamin B12b), dose-escalated vitamin C, and autologous stem cells in patients with stage IV pancreatic cancer and an inherited, deleterious BRCA1/2 mutation. Cancers that evolve in patients with a germline BRCA1/ 2 mutation generally have loss or inactivation of the wild type allele, which results in hypersensitivity to melphalan. The melphalan dose-response is log-linear: doubling the melphalan area under the curve (AUC) doubles the log reduction in clonogenic survival. The melphalan AUC that can safely be achieved with melphalan followed by stem cell rescue has the potential to provide major log reductions in cancer cell survival in BRCA-deficient cancers. However, reversion mutations in BRCA can cause resistance to DNA-crosslinking agents such as melphalan. Studies have shown that oxidizing cellular glutathione (GSH) to glutathione disulfide (GSSG) can inhibit DNA repair and hypersensitize wild-type cancer cells to melphalan. In this trial, BCNU, vitamin B12b, and vitamin C are used to increase cancer cell GSSG levels. Methods: Eligibility criteria include stage IV pancreatic cancer, an inherited deleterious BRCA1/2 mutation, life expectancy of at least 6 months, measurable or non-measurable disease, and suitability for apheresis, chemotherapy, and stem cell infusion. Prior treatment with PARP inhibitors is allowed. Stem cells are collected by apheresis. Participants receive 2 cycles of melphalan 100 mg/m2, BCNU 150 mg/m2, vitamin B12b 1.45 g/m2, and vitamin C 3, 6, or 8 g/m2 on Day −2. Stem cell infusion administered on day 0. A 2 + 4 dose-escalation schedule is employed for vitamin C. Adverse reactions summarized by CTCAE 5.0. The primary endpoint is safety, and secondary endpoints are objective response rate (overall and for metastatic lesions) and overall and progression-free survival. Amendment pending to include stage IV, BRCA-related, HER2-negative breast cancer and PALB2 mutations. The trial is enrolling at Memorial Sloan Kettering Cancer Center and Massachusetts General Hospital. Clinical trial information: NCT04150042 .
Sonoporation for disrupting the pancreatic cancer microenvironment to enhance chemotherapy delivery and improve outcomes.
Authors: Posey James , Machado Priscilla , Eisenbrey John R. , Bashir Babar , Mille Patrick Johnston , Basu Mallick Atrayee , Singla Rajan , Kotopoulis Spiros , Nordaas Ingrid K. , Trelsgård Audun M. , Jouleh Tæraneh , Dimcevski Georg Gjorgji , Gilja Odd-Helge , Forsberg Flemming 
Published: January 2023

TPS777 Background: Pancreatic ductal adenocarcinoma (PDAC) is 3% of cancers diagnosed in the United States and it is the fourth leading cause of cancer-related deaths. Hence, there is a considerable clinical need to develop innovative strategies for effective drug delivery and treatment. Sonoporation is a novel method that can enhance the therapeutic efficacy of co-administered chemotherapy by localized contrast-enhanced ultrasound imaging (CEUS) of gas-filled microbubbles (ultrasound contrast agent UCA), which temporarily changes tumor vascular microenvironment by increasing angiogenic vessel leakage through microstreaming, shockwaves and the activation of various intracellular signaling responses. Our Phase I clinical trial of sonoporation in 10 PDAC patients treated with Gemcitabine demonstrated no additional toxicity and an increase in median survival compared to 63 historical controls (8.9 vs 17.6 months; p = 0.011). Animal studies investigated 4 commercial UCAs under 2 different acoustic regimes and established the optimal UCA (Sonazoid, GE Healthcare, Oslo, Norway) as well as acoustic settings for sonoporation of PDAC. Methods: This Phase II clinical trial aims to improve standard of care (SoC) chemotherapy treatment by adding sonoporation (i.e., augmenting the SoC treatment with CEUS and microbubbles). Two sites (one in USA and one in Norway) will enroll 120 subjects with PDAC stage III or IIV prior to starting SoC chemotherapy. Exclusion criteria include known allergies to the UCA. The primary objective is to evaluate the safety and therapeutic efficacy of sonoporation on PDAC SoC treatment based on local progression-free and overall survival. Two groups: SoC chemotherapy or SoC chemotherapy followed by sonoporation. The optimal CEUS and microbubble conditions will be applied to a single PDAC tumor imaged by ultrasound. Treatment delivered day of SoC chemotherapeutic treatment for PDAC when the concentration of drugs is maximum. Gehan-Breslow-Wilcoxon test and Log-rank test will be used to compare survival. All clinical variables (e.g., concomitant imaging results, blood tests, etc.) will also be compared between groups with and without sonoporation. Clinical trial information: NCT04821284 .
Self-Sourced Medication Abortion, Physician Authority, and the Contradictions of Abortion Care
Authors: Karlin Jennifer , Joffe Carole 
Published: January 2023

Abstract
The growing acknowledgment of the phenomenon of individuals terminating their pregnancies by obtaining the medications necessary for an abortion—which this article refers to as “self-sourced medication abortion” (SSMA)—has shed light on the current contradictions in the world of abortion provision. This article offers a brief historical overview of the relationship between abortion provision and mainstream medicine, pointing to the factors that have led to the marginalization of abortion care. It then discusses interviews with 40 physicians who provide abortions about their perspectives on SSMA, and it explores how this group responds to the contradictions presented by SSMA. In doing so, it interrogates the changing meaning of “physician authority” among this subset of physicians. The authors suggest that these interviewees represent an emergent sensibility among this generation of abortion physicians, a sensibility strongly tied to a commitment to social justice.
History and Politics of Medication Abortion in the United States and the Rise of Telemedicine and Self-Managed Abortion
Authors: Baker Carrie N. 
Published: January 2023

AbstractThis article examines the decades-long campaign to increase access to abortion pills in the United States, including advocates' work to win US Food and Drug Administration approval of mifepristone and misoprostol for abortion, the continuing restrictions on mifepristone, and the multiple strategies advocates have pursued to challenge these restrictions, including lobbying the FDA to remove the restrictions, obtaining a limited research exemption from FDA restrictions, and suing the FDA during the COVID-19 pandemic. The article pays particular attention to the influence of research conducted on the safety and efficacy of medication abortion as well as research on the impact of increased availability of abortion pills through telemedicine during the pandemic. The article also addresses self-managed abortion, wherein people obtain and use mifepristone and/or misoprostol outside the formal health care system, and it documents the growing network of organizations providing logistical, medical, and legal support to people self-managing abortion. The article concludes with reflections on the role abortion pills might play in the post-Roe era amid increasingly divergent abortion access trends across different regions of the United States.
Emergency esophagectomy: Experience of a high volume esophageal cancer center
Authors: Ullah Faizan , Naeem Awais , Bakhtiar Nighat , Osama Shakeel  , UlHaq Ihtisham , Khattak Shahid , Aamir Ali Syed  
Published: January 2023

Objective: The objective of the study was to review the experience of dealing oncological emergency esophagectomies at a dedicated Cancer hospital.
Methods: We performed a retrospective review of data of eleven esophagectomies at the Department of Surgical Oncology, Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore (SKMCH&RC) Pakistan, from 1st January, 2009 to 30th June, 2019. Out of 590 oncological esophagectomies, eleven patients had emergency resection. We collected the data of demographics, primary disease, comorbidities, location of tumor and perforation, cause of perforations, radiological and endoscopic findings, clinical findings and follow-up visits after discharge. Data was analyzed by SPSS version 21 for windows.
Results: All 11 patients out of five hunded ninety had esophageal cancer. At the time of initial staging, eight (72%) had locally advanced stage (stage III and IV). Open transhiatal approach was used in six (55%) patients, and the rest had three stage esophagectomies. Primary reconstructions with gastric conduit were performed in all, except in two (18%) patients, Respiratory complications were the most common of the encountered complications, seven (63%) of the patients had palliative resection. Ninety day mortality was observed in 3(27.3%) patients. On long term follow up, six patients had recurrence, with median Disease-Free Survival (DFS) 5.88 months and Median Overall Survival (OS) was 6.37 months. Out of 11, only three patients are alive without disease, while one patient is lost during follow-up.
Conclusion: Emergency esophagectomy is a lifesaving procedure; there should be multidisciplinary team approach towards the management. Early diagnosis and management is of paramount importance.
doi: https://doi.org/10.12669/pjms.39.2.6613
How to cite this: Ullah F, Naeem A, Bakhtiar N, Shakeel O, Ihtisham-Ul-Haq, Khattak S, et al. Emergency esophagectomy: Experience of a high volume esophageal cancer center. Pak J Med Sci. 2023;39(2):---------. doi: https://doi.org/10.12669/pjms.39.2.6613
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Comparison of the effects of two extraction methods on the alveolar ridge preservation of Maxillary Anterior Teeth
Authors: Jiang Si , Zhou Biao , Li Zheng , Gao Juan , Wang Pei 
Published: January 2023

Objective: To compare the effects of high-speed turbodrill root extraction and piezosurgery tooth socket enlargement on the alveolar ridge preservation of maxillary anterior teeth.
Methods: Thirty-six clinically eligible patients admitted to the No.2 Hospital of Baoding or the Baoding First Central Hospital from January 2018 to November 2019 were selected and randomly divided into two groups. Group-A were extracted by high-speed turbodrill root extraction, while Group-B were extracted by piezosurgery tooth socket enlargement. After extraction, GBR bone grafting and soft tissue transplantation were performed on the extraction sockets. The extraction time, integrity rate of labial bone plate of the extraction socket, pain-free rate, satisfaction rate, reduction of the height and width of the alveolar ridge, alveolar bone mineral density score, and new bone contour score of the alveolar bone of two groups were compared.
Results: Group-B was significantly superior to Group-A in terms of tooth extraction time, pain-free rate, satisfaction rate and reduction of alveolar ridge height at three sites on the palatal side, with a statistically significant difference (p<0.05).
Conclusions: Piezosurgery tooth socket enlargement is more worthy of clinical application due to its advantages of less impact on the preservation of the palatal alveolar ridge height of the maxillary anterior teeth, shorter tooth extraction time, postoperative pain-free rate and high final satisfaction rate.
doi: https://doi.org/10.12669/pjms.39.2.6643
How to cite this: Jiang S, Zhou B, Li Z, Gao J, Wang P. Comparison of the effects of two extraction methods on the alveolar ridge preservation of Maxillary Anterior Teeth. Pak J Med Sci. 2023;39(2):---------. doi: https://doi.org/10.12669/pjms.39.2.6643
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.