Trauma surgeons share lessons learned from the Las Vegas mass shooting tragedy
at American College of Surgeons conference.
The session highlighted real-world insights from Nevada trauma surgeons who
treated seriously injured patients as a result of the deadliest mass shooting
in modern U.S. history at an outdoor music festival in Las Vegas on October 1.
“In the rst 24 hours, we saw 212 patients and performed 58 surgeries,” said Matthew Johnson, MD, FACS, with the Sunrise Hospital and Medical Center, Las Vegas. Sunrise staff grouped pods of operating rooms together for treating specic types of cases. “More than 100 physicians and more than 200 nurses responded to assist for a total of 83 surgeries performed. Everyone did their jobs. As for the residents—we couldn’t have gotten through this [incident] without them,”Dr. Johnson said.
Appendicitis is inflammation of the appendix. It may be acute or chronic.
Appendicitis can happen at any time, but it occurs most often between the ages of 10 and 30. It’s more common in males than in females.
If left untreated, appendicitis may cause your appendix to burst and cause infection. This can be serious and sometimes fatal.
The classic symptoms of appendicitis include:
- Dull pain near the navel or the upper abdomen that becomes sharp as it moves to the lower right abdomen. …
- Loss of appetite.
- Nausea and/or vomiting soon after abdominal pain begins.
- Abdominal swelling.
- Fever of 99-102 degrees Fahrenheit.
- Inability to pass gas.
Treatment for appendicitis varies. In most cases, however, surgery will be necessary. The type of surgery will depend on the details of your case.
It’s not only about the gut anymore. Even the pancreas has a microbiome, one that influences pancreatic cancer progression and that can be manipulated to resensitize the immune response in pancreatic adenocarcinoma.
A new study shows that pancreatic cancer harbors a 1000-fold higher concentration of bacteria compared with the normal pancreas. Moreover, the bacterial species in the pancreatic microbiome can shut down the immune response so that the pancreatic carcinoma milieu becomes ruled by immune suppression.
These observations were first made in animal models and were then extended to human patients with pancreatic ductal adenocarcinoma, which is typically fatal within 2 years.
In animal models, when the microbiome is ablated, the immune response is restored, and the animals are able to respond to immunotherapy.
One of the study’s corresponding authors, George Miller, MD, leader of the Tumor Immunology Program at NYU Langone Health’s Perlmutter Cancer Center, New York City, told Medscape Medical News: “Genetic mutations are not the sole components that explain pancreatic cancer progression, as mutations alone are insufficient for disease progression. One also needs an immune system that exhibits tolerance to the tumor.”
The study was published online March 22 in Cancer Discovery.
The researchers first showed that bacteria, when fed to mice, migrate from the gut to the pancreas, and that the microbiome of normal mice was distinct from that of mice with pancreatic cancer that expresses mutant KRAS, which is the commonly mutated gene in pancreatic cancer.
To characterize the human pancreatic microbiome, the researchers, using 16S rRNA gene sequencing, showed that the pancreatic microbiome in human patients was distinct from that of persons without pancreatic cancer. (Miller explained that normal pancreatic microbiome was determined from analyses of the pancreatic microbiomes of individuals who presented for surgery for benign endocrine tumors.)
To support the notion that the pancreatic microbiome promotes progression to pancreatic dysplasia, the researchers used two mouse models — a cohort expressing mutant KRAS, and a cohort that harbored mutant KRAS as well as mutant TP53.
Tumor progression was seen in both animal models, compared with control mice, but was quicker in the cohort with both mutations. However, for animals treated with an oral antibiotic, tumor burdens were reduced by ~50%. “These studies showed that the oral antibiotic regimen was able to slow pancreatic tumor growth,” Miller said.
The researchers also showed that longitudinal pertubations in the pancreatic and gut microbiome are associated with pancreatic dysplasia over time. They did this by serially profiling fecal bacteria in mice with pancreatic cancer and in control mice over 9 months. Although the bacterial community in the gut of mice with pancreatic cancer was similar in early life to that of wild-type mice, the gut microbiomes diverged over time, and after week 20, the microbiome of mice with pancreatic cancer was distinct from that of wild-type animals.
Extending these observations to humans, the researchers showed that Proteobacteria organisms composed ~8% of gut bacteria of pancreatic ductal adenocarcinoma patients but that they increased to 50% in cancerous pancreas. When the researchers obtained samples of both feces and tumors, they were able to show a differential migration of the bacteria to the pancreas. In progression toward the oncogenic phenotype, bacteria such as Proteobacteria, Actinobacteria, and Fusobacteria spp predominate the pancreatic microbiome.
Immune Involvement Explained
But how does one show that these bacteria are responsible in some measure for promoting pancreatic oncogenesis? Toward this end, the researchers ablated gut bacteria from mice with pancreatic cancer using oral antibiotics and repopulated cohorts using feces derived either from wild-type mice or cancer-bearing mice. They found that bacterial ablation (with antibiotic) protected against disease progression. They also found that repopulating with feces from mice that had pancreatic cancer accelerated tumor growth, whereas repopulating with feces from wild-type animals did not.
Miller explained that when they analyzed the immune compartment of animals with pancreatic cancer, they were able to show that ablation resulted in an increase of intratumoral T cells and a reduction in myeloid-derived suppressor cells, suggesting a change in the tumor microenvironment from immune suppression to immune activation.
An analysis of tumor-associated macrophages also confirmed a change in the type of macrophages that were recruited to the pancreatic tumor microenvironment after bacterial ablation. T-cell and chemokine profiling confirmed changes in the tumor microenvironment to one in which the immune system was activated, not suppressed.
“While combinations of changes in genes like KRAS cause cells to grow abnormally and form pancreatic tumors, our study shows that bacteria change the immune environment around cancer cells to let them grow faster in some patients than others, despite their having the same genetics,” Miller said.
The bacterial species abundant in the pancreatic microbiome release membrane components such as lipopolysaccharides and proteins such as flagellin that shift macrophages — key immune cells in the pancreas — to increase immune suppression, the authors note.
Miller explained that their experiments pointed out that suppression occurs through toll-like receptors. Suppressor macrophages bind to by-products of bacteria, and the complex induces T-cell suppression, he said.
The animal model explains how the pancreatic microbiome may establish itself in patients. “Our bacterial translocation experiments suggest interactions between the two compartments [pancreas and intestines], presumably via the pancreatic duct which is in anatomic continuity with the intestinal tract,” the researchers write.
In addition, when ablated animals were tested for programmed death–1 (PD-1) expression, the expression of PD-1 tripled, and response to PD-1-based immunotherapy was observed. This allowed the researchers to determine how to extend their observations to patients with pancreatic adenocarcinoma.
“Our results have implications for understanding immune suppression in pancreatic cancer and its reversal in the clinic,” commented senior coauthor Deepak Saxena, PhD, associate professor of basic science and craniofacial biology at the New York University College of Dentistry, New York City.
“Studies already underway in our labs seek to confirm the bacterial species most able to shut down the immune reaction to cancer cells, setting the stage for new bacteria-based diagnostic tests, combinations of antibiotics and immunotherapies, and perhaps for probiotics that prevent cancer in high-risk patients,” he said in a statement.
Miller agreed. “Our study shows that the pancreatic microbiome can be a target for therapy and offers a clue about how to use immunotherapy in pancreatic cancer, which has thus far remained unresponsive to immunotherapy,” he told Medscape Medical News.
Miller noted that the team is in the process of fine-tuning a study protocol that will determine whether giving a combination of antibiotics such as ciprofloxacin and metronidazole to patients with resectable pancreatic adenocarcinoma will improve the efficacy of a PD-1 inhibitor. They plan to recruit about 30 patients into the study.
The authors have disclosed no relevant financial relationships.
Cancer Discov. Published online March 22, 2018. Abstract
Endoscopic Retrograde Cholangiopancreatography (ERCP)
What is ERCP?
What are the bile and pancreatic ducts?
Your bile ducts are tubes that carry bile from your liver to your gallbladder and duodenum. Your pancreatic ducts are tubes that carry pancreatic juice from your pancreas to your duodenum. Small pancreatic ducts empty into the main pancreatic duct. Your common bile duct and main pancreatic duct join before emptying into your duodenum.
Why do doctors use ERCP?
Doctors use ERCP to treat problems of the bile and pancreatic ducts. Doctors also use ERCP to diagnose problems of the bile and pancreatic ducts if they expect to treat problems during the procedure. For diagnosis alone, doctors may use noninvasive tests—tests that do not physically enter the body—instead of ERCP. Noninvasive tests such as magnetic resonance cholangiopancreatography (MRCP)—a type of magnetic resonance imaging (MRI) —are safer and can also diagnose many problems of the bile and pancreatic ducts.
Doctors perform ERCP when your bile or pancreatic ducts have become narrowed or blocked because of
Matthew Johnson, MD: DSA Trauma, Critical Care & Robotic Surgeon
Robotic surgery is a method of performing surgery using very small tools attached to a robotic arm. The surgeon controls the robotic arm with a computer.
The surgeon makes small cuts to insert the instruments. A thin tube with a camera attached to the end of it (laparoscope) allows the surgeon to view enlarged 3-D images of your body as the surgery is taking place. The robot matches the doctor’s hand movements to perform the procedure using the tiny instruments.
The surgeon can make small, precise movements using this method. This can allow the surgeon to do a procedure through a small cut that once could be done only with open surgery. It is easier for the surgeon to use the surgical tools with robotic assist than with laparoscopic surgery through an endoscope. The surgeon can also see the area where the surgery is performed more easily. This method lets the surgeon move in a more comfortable way, as well.
Because surgery is done with precision, miniaturization and smaller incisions benefits include:
- Decreased blood loss, less pain, and quicker healing time
- Decreased risk of infection
- Smaller Scars
- Hospital stays are shortened, blood loss is reduced, transfusions are reduced, and use of pain medications are reduced.
Compared with other minimally invasive surgery approaches, robot-assisted surgery gives the surgeon better control over the surgical instruments and a better view of the surgical site. In addition, surgeons no longer have to stand throughout the surgery and do not tire as quickly.
Robotic smart instruments also reduce or eliminate the tissue trauma traditionally associated with open surgery.
Any time an internal body part pushes into an area where it doesn’t belong, it’s called a hernia.
The hiatus is an opening in the diaphragm — the muscular wall separating the chest cavity from the abdomen. Normally, the esophagus (food pipe) goes through the hiatus and attaches to the stomach. In a hiatal hernia (also called hiatus hernia) the stomach bulges up into the chest through that opening.There are two main types of hiatal hernias: sliding and paraesophageal (next to the esophagus).
In a sliding hiatal hernia, the stomach and the section of the esophagus that joins the stomach slide up into the chest through the hiatus. This is the more common type of hernia.
The paraesophageal hernia is less common, but is more cause for concern. The esophagus and stomach stay in their normal locations, but part of the stomach squeezes through the hiatus, landing it next to the esophagus. Although you can have this type of hernia without any symptoms, the danger is that the stomach can become “strangled,” or have its blood supply shut off.
Many people with hiatal hernia have no symptoms, but others may have heartburn related to gastroesophageal reflux disease, or GERD. Although there appears to be a link, one condition does not seem to cause the other, because many people have a hiatal hernia without having GERD, and others have GERD without having a hiatal hernia.
What is a therapeutic ERCP?
Endoscopic retrograde cholangiopancreatography, or ERCP, is a study of the ducts that drain the liver and pancreas. Ducts are drainage routes into the bowel. The ones that drain the liver and gallbladder are called bile or biliary ducts. The one that drains the pancreas is called the pancreatic duct. The bile and pancreatic ducts join together just before they drain into the upper bowel, about 3 inches from the stomach. The drainage opening is called the papilla. The papilla is surrounded by a circular muscle, called the sphincter of Oddi.
Diagnostic ERCP is when X-ray contrast dye is injected into the bile duct, the pancreatic duct, or both. This contrast dye is squirted through a small tube called a catheter that fits through the ERCP endoscope. X-rays are taken during ERCP to get pictures of these ducts. That is called diagnostic ERCP. However, most ERCPs are actually done for treatment and not just picture taking. When an ERCP is done to allow treatment, it is called therapeutic ERCP.
What treatments can be done through an ERCP scope?
Sphincterotomy is cutting the muscle that surrounds the opening of the ducts, or the papilla. This cut is made to enlarge the opening. The cut is made while your doctor looks through the ERCP scope at the papilla, or duct opening. A small wire on a specialized catheter uses electric current to cut the tissue. A sphincterotomy does not cause discomfort, you do not have nerve endings there. The actual cut is quite small, usually less than a 1/2 inch. This small cut, or sphincterotomy, allows various treatments in the ducts. Most commonly the cut is directed towards the bile duct, called a biliary sphincterotomy. Occasionally, the cutting is directed towards the pancreatic duct, depending on the type of treatment you need.
The most common treatment through an ERCP scope is removal of bile duct stones. These stones may have formed in the gallbladder and traveled into the bile duct or may form in the duct itself years after your gallbladder has been removed. After a sphincterotomy is performed to enlarge the opening of the bile duct, stones can be pulled from the duct into the bowel. A variety of balloons and baskets attached to specialized catheters can be passed through the ERCP scope into the ducts allowing stone removal. Very large stones may require crushing in the duct with a specialized basket so the fragments can be pulled out through the sphincterotomy.
Stents are placed into the bile or pancreatic ducts to bypass strictures, or narrowed parts of the duct. These narrowed areas of the bile or pancreatic duct are due to scar tissue or tumors that cause blockage of normal duct drainage. There are two types of stents that are commonly used. The first is made of plastic and looks like a small straw. A plastic stent can be pushed through the ERCP scope into a blocked duct to allow normal drainage. The second type of stent is made of metal wires that looks like the cross wires of a fence. The metal stent is flexible and springs open to a larger diameter than plastic stents. Both plastic and metal stents tend to clog up after several months and you may require another ERCP to place a new stent. Metal stents are permanent while plastic stents are easily removed at a repeat procedure. Your doctor will choose the best type of stent for your problem.
There are ERCP catheters fitted with dilating balloons that can be placed across a narrowed area or stricture. The balloon is then inflated to stretch out the narrowing. Dilation with balloons is often performed when the cause of the narrowing is benign (not a cancer). After balloon dilation, a temporary stent may be placed for a few months to help maintain the dilation.
One procedure that is commonly performed through the ERCP scope is to take samples of tissue from the papilla or from the bile or pancreatic ducts. There are several different sampling techniques although the most common is to brush the area with subsequent examination of the cells obtained. Tissue samples can help decide if a stricture, or narrowing, is due to a cancer. If the sample is positive for cancer it is very accurate. Unfortunately, a tissue sampling that does not show cancer may not be accurate.