Central Nervous System Depressants

All Drugs and Chemicals

Anesthetics

Patients assigned to this group receive combined epidural-general anesthesia and postoperative patient-controlled epidural analgesia.

Patients assigned to this group receive general anesthesia and postoperative patient-controlled intravenous analgesia.

Combined epidural-general anesthesia and postoperative epidural analgesia.

Combined epidural-general anesthesia

General anesthesia and postoperative intravenous analgesia.

General anesthesia

Dong-Xin Wang, MD, PHD

Surgical resection is one of the most important treatments for solid organ cancer. Whereas cancer recurrence and/or metastasis are the major reasons of treatment failure. The outcomes after surgery are mainly dependent on the balance between the immune function of the body and the invasiveness of residual cancer. Preclinical and retrospective studies suggest that anaesthetic techniques and drugs may affect the long-term outcomes in patients undergoing cancer surgery. The investigators hypothesize that epidural anesthesia-analgesia may improve long-term survival in the elderly who undergo major surgery for cancer.

Surgical resection is the main treatment for potentially curable solid organ cancer. However, long-term survival after cancer surgery is far from satisfactory. Quite a number of patients develop tumor metastasis and/or recurrence after surgery, which are associated with poor long-term outcomes. The development of tumor recurrence and/or metastasis after surgery is mostly dependent on the balance between the anti-tumor immune function of the body and the ability of implantation, proliferation and neovascularization of the residual cancer cells.

Studies showed that anaesthetic techniques and drugs may influence the cellular immune function and long-term outcomes. For example, it was found that ketamine and thiopental, but not propofol, suppresses natural killer (NK) cell activity; all three drugs caused a significant reduction in NK cell number; isoflurane and halothane inhibit interferon stimulation of NK cell cytotoxicity; nitrous oxide interferes with deoxyribonucleic acid, purine, and thymidylate synthesis and depresses neutrophil chemotaxis; opioids have been shown to suppress cell-mediated and humoral immunity.

Considering the potential harmful effects of general anesthesia/anesthetics, there is increasing interest on the effect of regional anaesthesia. Retrospective studies investigating the relationship between epidural anesthesia and outcomes after cancer surgery provide different results. In a meta-analysis of retrospective studies, regional anesthesia was associated with improved survival, but had no effect on the occurrence of cancer recurrence/metastasis. The investigators hypothesize that epidural anesthesia may produce favorable effects on long-term survival in the elderly who undergo major surgery for cancer under general anesthesia. However, there are no sufficient evidences in this aspect.

Epidural Anesthesia and Long-term Outcomes in Elderly Patients After Surgery

Impact of Epidural Anesthesia-analgesia on Long-term Outcomes in Elderly Patients After Surgery: 5-year Follow-up of a Multicenter Randomized Controlled Trial

Time from surgery to the date of all-cause death.

Time from surgery to the date of cancer-specific death. Patients who die from other causes being censored at the time of death.

Time from surgery to the date of cancer recurrence/metastasis or all-cause death, whichever comes first.

Time from surgery to the first date of cancer recurrence/metastasis, new onset cancer, new serious non-cancer disease, or death from any cause.

Cognitive function is assessed with the modified Telephone Interview for Cognitive Status (TICS-m; a 12-item questionnaire that assesses global cognitive function by verbal communication via telephone. The score ranges from 0 to 50, with higher score indicating better function).

Quality of life is assessed with the World Health Organization Quality of Life brief version (WHOQOL-BREF; a 24-item questionnaire that assesses the quality of life in physical, psychological, social relationship and environmental domains. The score ranges from 0 to 100 for each domain, with higher score indicating better function).

Peking University People's Hospital

Peking University Third Hospital

Beijing Hospital

Beijing Shijitan Hospital, Capital Medical University

Peking University First Hospital

Professor

Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Digestive System Diseases

Rare Diseases

Breast Neoplasms

Stomach Neoplasms

Liver Neoplasms

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Stomach Diseases

Liver Diseases

Stomach Cancer

Hematinics

Liver Extracts

Udo Rudloff, M.D.

Background:

* Researchers are trying to learn what causes certain types of cancer to spread to other organs in the body (metastasis). Cancer tumors may produce a very small number of specific cells (cancer stem cells) that cause the tumors to grow in other organs throughout the body.
* By examining cancer tumor tissue, normal tissue, blood, bone marrow, and other body fluids, researchers may determine whether these samples contain cancer stem cells. Cancer stem cells may provide information on whether the cancer will come back or spread before other routine x-ray studies or lab tests indicate its presence.

Objectives:

* To acquire a collection of solid organ cancer stem cells for future study.
* To analyze solid organ cancer stem cells from various types of cancer on a genetic level.
* To determine if solid organ cancer stem cells are present in the blood or bone marrow.

Eligibility:

* Patients 16 years of age and older who have solid organ cancer (cancer in the liver, colon, rectum, anus, pancreas, stomach, breast, skin, muscles, fat, connective tissue, uterus, ovary, cervix, vagina, vulva, or inner lining of the abdomen) or a precancerous growth, and who are scheduled to have a biopsy or surgery to remove the cancer as part of their treatment.

Design:

* This is a prospective trial designed to procure solid organ cancer stem cells before either surgery or biopsy.
* All patients registered to this trial will undergo surgery to extirpate their cancer in the NCI
* Prior to surgery or biopsy, 8 tablespoons of blood will be drawn.
* During the surgery or biopsy, a sample of normal tissue will be removed along with the cancerous or precancerous tissue. If separate consent is given, samples of bone marrow will also be taken.
* After discharge, patients will return to the clinic for routine visits every month for the first 3 months following surgery, and then about every 3 months for 2 years, and then every 6 months for 3 years. During the visits, patients will have routine blood and imaging studies done, and researchers will take additional blood samples (about 8 tablespoons at each visit) and optional bone marrow samples (4 teaspoons every 6 months) to be used for research.

Background:

* Traditional models of cancer metastasis posit that cancer metastases might originate stochastically in any cancer cell while, the Cancer-Stem-Cell hypothesis suggests that the metastasizing cells are Solid Organ Cancer Stem Cells (SOCSC).
* SOCSC are relatively resistant to current cancer therapies. Thus, effective treatment for metastatic cancers might require the targeting of SOCSC.
* Knowledge on SOCSC is chiefly derived from cell lines. However, data suggest vast differences between cell lines and SOCSC obtained from fresh tumors.
* This protocol is designed to facilitate fresh tissue procurement to study SOCSC.

Primary Objective:

-To study the natural history of SOCSC from various primary and metastatic solid organ cancers using established phenotypic and functional markers.

Secondary Objectives:

* To analyze SOCSC for potential targets that can be used to design novel cancer therapies that target cancer stem cells.
* To determine whether SOCSC are present in the blood and/or bone marrow, and study their quantitative and/or qualitative changes from time of surgical resection to time of recurrence and/or metastasis.
* To evaluate the potential of SOCSC and their quantitative and/or qualitative changes over time after surgery, to be used in future studies as biomarkers for the early detection of cancer recurrence and/or metastases.
* To collect detailed history, demographic, and treatment data as well as perioperative findings to evaluate potential correlation with the presence or absence of SOCSC.
* To develop an animal model to investigate potential interaction between bone marrow derived stem cells and solid organ cancers.
* To observe the course of normal stem cells over time in patients who had benign tumors that do not show evidence of cancer over time.
* To compare the course of normal stem cells with that of stem cells from patients with solid organ cancers.
* To specifically investigate families with clusters of cancer to determine if there is a relationship between SOCSC and potential familial genetic mutations specific to a particular cancer and if present, to compare these genetic abnormalities with individuals from the same family without cancer.

Eligibility:

* Patients 16 years of age or older with primary or metastatic solid organ cancers requiring resection or other cancer directed therapy that is deemed in the best interest of their cancer care.
* Patients with premalignant neoplasms who are scheduled to undergo surgery or biopsy as part of their diagnostic evaluation.
* Patients must have an ECOG performance score of 0-2.
* Patients must have laboratory and physical examination parameters within acceptable limits by standard of practice guidelines prior to biopsy or surgery.

Design:

* This is a prospective trial designed to procure SOCSC from various benign and solid organ cancers tumors (primary or metastatic) and follow their natural history from time of surgery and or other cancer directed therapy to time of recurrence.
* SOCSC will be isolated using phenotypic and functional markers. Investigations will be performed on the following tissues: Blood prior and after surgery, tumor and adjacent normal tissue when available, bone marrow (strictly optional under separate consent), and peritoneal washings when applicable.
* After surgery blood will be drawn at 1 and 3 months and every 3-6 months thereafter during the follow-up period (5 years). Bone marrow may be analyzed every six months during the follow-up period (strictly optional).
* Patients will be followed with standard of care or other cancer directed therapy deemed in the best interest of the patient.
* It is anticipated that between 274 and 676 patients will be enrolled over a period of 5 years (2-5 patients per month).

The Natural History of Solid Organ Cancer Stem Cells (SOCSC)

National Cancer Institute (NCI)

Symptoms and General Pathology

Neoplasm Metastasis

Neoplastic Processes

Antineoplastic Agents

Immune Checkpoint Inhibitors

Pembrolizumab

Autoantibodies

Avelumab

Nivolumab

Atezolizumab

Ipilimumab

Antineoplastic Agents, Immunological

All enrolled patients must have been diagnosed with a cancer potentially treatable with ipilimumab, nivolumab, pembrolizumab, atezolizumab or avelumab, alone or in combination, per standard protocol.

Treatment with approved immune checkpoint inhibitors, namely ipilimumab, nivolumab, pembrolizumab, atezolizumab and avelumab, alone or in combination, administered per standard protocol.

Treatment with immune checkpoint inhibitors.

Patients will undergo ordinary blood tests obtained at specific moments predefined per protocol and extraordinary blood tests at the time of the detection of an eventual irAE.

Blood tests.

Iñigo Les Bujanda, MD PhD

Inés Pérez Francisco

The aim of this study is to assess the effectiveness of a battery of autoantibodies to predict the occurrence of immune-related adverse events (irAEs) in patients with cancer who will be treated with immune checkpoint inhibitors (ICIs) per standard protocol.

Introduction: Treatment with ICIs is leading to a remarkable improvement in the prognosis of several types of cancer. However, the expansion of these drugs in the field of oncology is also causing the emergence of a large diversity of irAEs, whose optimal prevention and management are still to be clarified. Nowadays, there is a growing need for reliable and validated biomarkers to predict the occurrence of irAEs in patients treated with ICIs.

Purpose: To assess the effectiveness of a battery of autoantibodies available in a laboratory of autoimmunity to predict the occurrence of irAEs in patients with cancer who will be treated with ICIs per standard protocol.

Methods: A multicenter prospective observational cohort study was designed to include a total of 221 patients diagnosed with cancer amenable to treatment with ICIs. During a period of 48 weeks, patients will be controlled in the oncology outpatient clinics of five university hospitals with accredited experience in the management of immunotherapy. Immune-related adverse events will be defined and categorized according to CTCAE v. 5.0. Considering a proportion of irAEs and losses to follow-up of 25% and 5% respectively, a sample size of 221 patients was calculated to estimate an expected sensitivity of the autoantibody battery of 0.90 with a 95% confidence interval not lower than 0.75. All the participants will undergo ordinary blood tests at specific moments predefined per protocol and extraordinary blood tests at the time of the detection of an eventual irAE. Both ordinary and extraordinary samples will be frozen and stored in the biobank of each participating hospital in the form of serum and buffy coat. Once the whole cohort reaches the 24th week (intermediate analysis) and the 48th week (definitive analysis), all the samples will be centralized in the same autoimmunity laboratory for the determination of the autoantibody battery. A predictive model of irAEs will be constructed with the autoantibodies together with other potential risk factors of immune-mediated toxicity.

Autoantibodies in Treatment With Immune Checkpoint Inhibitors (AUTENTIC)

Prediction of Immune-related Adverse Events Induced by Anti-CTLA4 and Anti-PD1/PDL1 Drugs by Means of a Battery of Autoantibodies. A Multicenter Prospective Observational Cohort Study

All collected IPD will be available for exploitation in future research projects. This statement also includes the availability of the study protocol, the statistical analysis plan, the informed consent form, the clinical study report and the analytic code.

An irAE was defined as any symptom, sign, syndrome or disease attributable to an immune activation mechanism during an ongoing treatment with an ICI or a combination of ICIs, provided that an infectious cause and/or tumor progression have been ruled out.

Time in months from the initiation of therapy with ICIs until the occurrence of an irAE or until the date of the last follow-up.

Time in months from the initiation of therapy with ICIs until the date of proven tumor progression or until the date of the last follow-up.

Time in months from the initiation of therapy with ICIs until the date of patient's death or until the date of the last follow-up.

Positive conversion of the autoantibody battery after the initiation of therapy with ICIs.

Hospital de Basurto

Hospital Donostia

Complejo Hospitalario de Navarra

Hospital Galdakao-Usansolo

Hospital Universitario Araba

Principal Investigator

Nervous System Diseases

Behaviors and Mental Disorders

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Respiratory Tract (Lung and Bronchial) Diseases

Heart and Blood Diseases

Immune System Diseases

Nutritional and Metabolic Diseases

Infections

Dementia

Kidney Diseases

Critical Illness

Lung Diseases, Obstructive

Pulmonary Disease, Chronic Obstructive

Parkinson Disease

Heart Failure

Emergencies

Sclerosis

Multiple Sclerosis

Heart Arrest

Hepatic Encephalopathy

Sepsis

Toxemia

Multiple Organ Failure

Lung Diseases

Brain Diseases

Renal Insufficiency, Chronic

Renal Insufficiency

Parkinsonian Disorders

Ganglion Cysts

Synovial Cyst

Basal Ganglia Diseases

Central Nervous System Diseases

Movement Disorders

Synucleinopathies

Neurodegenerative Diseases

Autoimmune Diseases

Demyelinating Autoimmune Diseases, CNS

Autoimmune Diseases of the Nervous System

Demyelinating Diseases

Urologic Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Male Urogenital Diseases

Chronic Disease

Disease Attributes

Heart Diseases

Liver Failure

Hepatic Insufficiency

Brain Diseases, Metabolic

Metabolic Diseases

Respiratory Tract Diseases

Shock

Chronic Graft Versus Host Disease

Acute Graft Versus Host Disease

The interventional group (Ig) will have an early palliative care consultation ordered during their stay in the emergency department.

The control group will be treated as standard of care. Palliative care consultations may or may not be ordered at the attending physician's discretion.

Early order of palliative care consultation

Robert Zalenski, M.D., M.A.

A prospective randomized controlled trial studying the ordering of palliative care consultations in the emergency department (Ig) versus later palliative care consultations in the hospital--ICU or hospital ward(Cg). Patients will be randomly allocated to Ig or Cg with a 1:1 ratio.

Timing of Acute Palliative Care Consultation in Critically Ill Patients

A Randomized Allocation of Palliative Care Consultation in the Emergency Department Compared to Usual Practice

The proportion of patients who received an ACP CMS billing codes (which took effect in January 2016), in Ig vs. Cg will be evaluated using one or both of the new CPT codes for Advance care planning (ACP) services...including the explanation and discussion of advance directives such as standard forms (with the completion of such forms, when performed) by the physician or other qualified health profession; first 30 (15-45)minutes, face to face with the patients, family member(s) and/or surrogate Code 99497; and each additional 30 (46-75 minutes)-Code 99498 (Federal Register, 2015).

The investigators will align treatment preferences with medical orders, replicated as reported in the study by Mack et al. Proportions of patients coded as having a match will be compared across the treatment and control groups. For everyone who gets ACP during the study, patients or their surrogates will be asked by a member of the care team-either palliative care if they are consulted, or the hospital based care team if they are not: "If you could choose, would you prefer (a) treatment that focuses on attempting to extend your time as much as possible, even if doing so means more pain and discomfort, or (b) a plan of care that focuses on relieving pain and discomfort and improving quality of life, even though that may mean not living as long.

This outcome will be measured on a continuous scale. The net-promoter score will be measured at baseline (at randomization) and at hospital discharge for a change in value. It is measured on a scale of 1-10. Whoever signs the consent (patient of LAR) will be asked the net promoter score, and that will be reassessed by them at discharge, unless the patient has died-and the variable will then be recorded as missing. The PSQ will be administered by research assistants at the time of the patient's discharge. If the patient is incapacitated, then it will be asked of the patient's closest family caregiver. So PSQ is only at discharge of patient or available, most involved, family caregiver.

Blue Cross Blue Shield of Michigan Foundation

Wayne State University

Principle Investigator

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Epidural Anesthesia and Long-term Outcomes in Elderly Patients After Surgery	NCT03335826	Elderly Patient... Solid Organ Can... Surgical Resect... Epidural Anesth... Long-term Outco...	Combined epidur... General anesthe...	60 Years - 90 Years	Peking University First Hospital
The Natural History of Solid Organ Cancer Stem Cells (SOCSC)	NCT00923052	Hepatic Cancer Pancreatic Duct... Colorectal Canc... Breast Cancer Gastric Cancer		16 Years - 100 Years	National Institutes of Health Clinical Center (CC)
Autoantibodies in Treatment With Immune Checkpoint Inhibitors (AUTENTIC)	NCT03868046	Cancer Metastatic Canc... Solid Organ Can...	Treatment with ... Blood tests.	16 Years - 99 Years	Hospital Universitario Araba
Timing of Acute Palliative Care Consultation in Critically Ill Patients	NCT02858778	Multiple Organ ... End Stage Cardi... End Stage Chron... Chronic Kidney ... Hepatic Encepha... Sepsis Dementia Multiple Sclero... Parkinson's Dis... In-Hospital Car... Solid Organ Can...	Early order of ...	65 Years -	Wayne State University
Epidural Anesthesia and Long-term Outcomes in Elderly Patients After Surgery	NCT03335826	Elderly Patient... Solid Organ Can... Surgical Resect... Epidural Anesth... Long-term Outco...	Combined epidur... General anesthe...	60 Years - 90 Years	Peking University First Hospital
Autoantibodies in Treatment With Immune Checkpoint Inhibitors (AUTENTIC)	NCT03868046	Cancer Metastatic Canc... Solid Organ Can...	Treatment with ... Blood tests.	16 Years - 99 Years	Hospital Universitario Araba
Autoantibodies in Treatment With Immune Checkpoint Inhibitors (AUTENTIC)	NCT03868046	Cancer Metastatic Canc... Solid Organ Can...	Treatment with ... Blood tests.	16 Years - 99 Years	Hospital Universitario Araba

Spots Global Cancer Trial Database for solid organ cancer