Week 2 - Andrew

Last week was somewhat frustrating, as I didn't pursue my mentor forcefully enough to be kept up to speed on her activities (my mentor being Dr. Susan Pannullo). While this is partially my fault, in my defense I hadn't needed to send repeated emails or anything like that during week 1 to stay informed, so it took me a little while to determine how much force was necessary ... and to figure out that it was better to circumvent the administrative assistant. However this week wasn't a waste, in terms of clinical experience I sat in on "Tumor Board" and made some strides with my research project. Tumor Board is an interdisciplinary meeting on tougher neurooncology cases, where the imaging (largely MRI) is analyzed by many, along with the pathology and a brief patient history. From this information, the doctors determine what the next steps in treatment should be. In a few of the cases, clinical trials are identified that the patient is eligible for that the patient's doctor was not aware of. I have heard a call for the need of a list of all of the clinical trials in the neurooncology department, of which there are dozens, so that doctors will not be able to be unaware of what is going on, even if they are not involved in a particular trial. I wonder why this list hasn't already been created, its necessity is pretty apparent to me. I would like to help with this, I will talk to my mentor to find out if anyone is working on this, and if not how I might help.

My research is moving forward. As a bit of restatement, my project is to create, or at least begin to create, an inflatable polymer balloon that will have radioactive cesium-131 beads studded to its outer surface for brachytherapy. The challenge I have been working on is the logical first step: finding an appropriate polymer for this device. This polymer must be soft enough to be expanded into a cavity in the brain by hand, strong enough to keep its shape and so maintain the position of the radioactive beads within the cavity, biocompatible, and biodegradable within the correct timeframe. I had previously believed that I had found an appropriate polymer in poly-4-hydroxybutyrate, based on a few papers I had found in the literature. See my previous post for more details. However I hit a serious snag when I attempted to move ahead with purchasing this polymer. It turns out that all of the papers on P4HB use in medical devices are co-authored by someone from the company Tepha, and Tepha seems to be the only manufacturer of this polymer. When I went to the Tepha website there was nothing there about actual products for sale. I contacted the company about P4HB a few times, and ultimately they told me that yes, they are the only manufacturer of P4HB, and no, I could not have any. After such friendly and helpful remarks, I have decided to go back to the literature and identify another option or two for polymers for this device.

Week 2 - Brandon

The past week went well, definitely faster than the first week since I was more into the groove of things this week. On Monday, I saw a completely different side of this clinical experience in that we spent time watching a surgeon perform total disc replacements on rats. My mentor is on our research team in Ithaca so the rat tail implants were made before I came down so I got to see them from the beginning directly through implantation and I am also getting to follow along with post-op observations (MRI and X-ray) which is awesome. As one of my projects for the summer, I will be validating MRI as a means of measuring different intervertebral disc metrics using the scans that we take of the implanted/ control groups, so it was great it see everything happen from conception to get a full picture of the research. After the rat tail surgeries, I was able to go to the OR and watch Dr. Härtl perform a surgery and also some clinical patient visits. Tuesday and Wednesday are always patient visit days, and are often the most non-stop. The past week seemed to be a pretty even-mix of new patients and follow ups, with a few very interesting cases spattered throughout the days. Many of the interesting cases were presented at a spine conference in which surgeons, residents, fellows and students come together and brainstorm how a case should be handled or summarize a previous surgical case. This was a great way to understand the surgical though process, gain some vocabulary and see what other surgeons are up to. I was back in the OR on Thursday and Friday. There were some different types of surgeries happening in other OR rooms, including my first 3-D displayed surgery in which they removed a tumor in the pituitary gland of a patient. In the area of spinal surgery there was some complicated surgeries as well. One was a multi-level ALIF (anterior lumbar interbody fusion) procedure that was more involved (and more invasive) than the prior XLIF procedures. I also witnessed Dr. Härtl remove a tumor in the upper cervical region of a patient's spine (on the side of the posterior lateral ligament) that was compressing the spinal cord. The second week is an interesting point since many of the surgeries done were on patients that I may have seen during the previous week in pre-op visits. I am looking forward to what this next week has in store and to getting moving on my research projects.

Week 1 - Natalie

Due to a research collaboration requiring travel to Australia from June 9 – June 26, I began my first immersion week from June 1 – June 8. I will be performing my immersion in the lab of Dr. Mathias Bostrom at the Hospital for Special Surgery (HSS). One of my main goals, besides gaining a greater appreciation for the clinical side of orthopedics, is to learn the technique of quantitative reverse transcription polymerase chain reaction (qRT-PCR). Wednesday was mostly dedicated to securing an ID for HSS and meeting Dr. Bostrom's surgical assistant and starting the process of getting a scrub card. Thursday morning I attended grand rounds for the adult reconstruction and joint replacement service. This meeting is split into two segments. The first half hour is dedicated to case presentations, and the last hour is a research or clinical presentation on a specific topic. This week, the case presentations focused on the use of fluoroscopy in the operating room and several cases that could have benefited from this technology were presented. The clinical presentation was by two physicians, Dr. Alexiades and Dr. Sculco. Each surgeon presented their preferred method of minimally invasive total hip replacement surgery, with Dr. Alexiades championing the posterior approach, and Dr. Sculco focusing on the anterior approach. Even though each surgeon uses different approaches, both agreed that either technique could be successful and that a surgeon should use whatever approach they are most comfortable with. This meeting was especially interesting to me, as it was very clinically focused. I participated in a lab meeting for Dr. Bostrom's group on Friday morning. At this meeting, several current projects in the lab were discussed. From Monday-Wednesday I was able to get involved with lab work by assisting an orthopedic resident who is taking a year off for research in the first steps of the qRT-PCR protocol. This was great, since it is a main goal of mine to learn this technique this summer. The study that Dr. Kitay is performing qRT-PCR for was a fracture model in young and old mice. The bone tissue had already been harvested from the mice. The first steps of the protocol involved pulverizing the bone sample and putting the sample in Trizol, which is used to isolate the RNA. This process took one day, for twelve samples. The next day, we extracted the RNA from the trizol solution by adding chloroform and performing successive buffer washes and spin downs to extract the RNA. We then examined the RNA concentration, 280/260 peak, and 280/230 peak using a NanoDrop machine to get an idea of how successful we were at extracting RNA from the samples. We had excellent concentrations (much higher than expected) and adequate 280/260 and 280/230 peaks for all of the samples. Although this is a helpful measure and likely means that we performed the protocol successfully, the samples still need to be analyzed with an Agilent machine to get the RNA integrity number (RIN), which will confirm that our RNA extraction was successful. It was great to be able to get involved in the lab so quickly, and I look forward to performing the next steps of the protocol and seeing surgeries and attending clinic when I return from Australia!

Week 2 MultiDisciplinary Clinical Experience

This week was thought-provoking.

I went to clinic last Friday, thinking it would be like normal, seeing children who are being treated for hydrocephelaus. But instead, I walked into a multi-disciplinary clinic. I walked into the office to find a pediatric podiatrist, a neurosurgeon, a physical therapist, and an orthopedic surgeon, all waiting to see a one patient. About seven people walked into the patients room with the experts leading the way, asking questions, examining the patient. You could tell it was overwhelming for the families but they were also grateful to have so many eyes focused on their needs. They wouldn't need to be directed towards another specialist for another appointment two months later--the best of the best was already in the room. At first it was difficult to ask questions. They're so busy...and so experienced. But I got over that in enough time and their smile and earnestness won me over.

The multi-disciplinary clinic was also inspirational because of the patients. All of them had issues with spasticity and muscle tone, derived from some neurological disorder such as autism or cerebral palsy. My father was born with cerebral palsy in the 1950s, a time when it was recommended to let babies like him die. My Dad was a quadriplegic as a child and eventually gained the use of his upper body. He is still unable to walk and has the same spasticity issues as the patients I saw in clinic. I had empirically known about this disease all my life and there I was sitting in a room of experts, it was overwhelming. And they cared. Dr Leon Root specializes in cerebral palsy was two inches away from me discussing how treatments and societal norms have changed with these disorders over the last 50 year. After the doctors were done discussing the treatments, one mother invited them to see a play that she wrote. They brainstormed ways to get her a wheelchair for her son. They scolded a wheelchair bound young boy who wouldn't listen to his mother, who needed to learn how to take care of himself in his newly found state.

After the clinic was over, I saw other patients. I couldn't help but notice with some the end decision was "we need to talk to a neurologist" or "let's see what the ear, nose, and throat doctor says first." I like the idea of a multidisciplinary clinic because I think it maximizes the patients time and the doctors as well. It might also enhance the quality of the diagnosis. it certainly made the patients feel more valuable. I really felt like every patient left more motivated, more optimistic.

Week 2 - John

The surgery I watched on Friday involved removing a tumor beneath the cerebellum and adjacent to the brain stem. The patient was a 3-year-old boy, who already had a previous operation to biopsy the tumor. The tumor was benign, but was slowly increasing in size, and the boy was undergoing chemotherapy to manage it. However, a part of the tumor was turning necrotic, and needed to be removed. Because of the tumor's proximity to the brain stem, extra precaution had to be taken to avoid causing any damage to the cranial nerves.

As such, neurophysiologists had to constantly monitor the patient during the entire operation, which, including the setup, lasted from 7:30 am till 4:30 pm. It was the longest operation I had seen so far because of the degree of complexity involved. Before cutting into a new area, Dr. Souweidane had to probe the tissue to ensure that it was not involved in any motor or sensory function. The neurophysiologists had attached probes to different muscle groups controlled by the cranial nerves, as well as stimuli to different sensory nerves, to determine the baseline readings at the start of the operation, and any changes that occurred during the operation. Dr. Souweidane had to use a microscope, as well as micro scissors, spatulas, and even an ultrasonic aspirator to meticulously separate the tumor from the surrounding healthy brain tissue and nerves. While large parts of the tumor were excised in whole, the remaining tumor was liquefied and aspirated away by the ultrasonic aspirator. I later found out that this ultrasonic aspirator was originally meant for shaving bone down on a microscopic level, but certainly came in very useful in this brain surgery as well.

Because the surgery took a very long time, I had the opportunity to speak with Dr. Stein, the anesthesiologist. Apparently, anesthesia has to be properly controlled - too little of it, and the patient regains consciousness; too much of it, and the patient's core organs shut down. Usually, patients are not put under anesthesia for more than 24 hours. However, if a person had a feeding tube and a ventilator attached, he or she can be under anesthesia for months. In the case of inducing a coma in patients suffering from traumatic brain injury, the rational is that when there is less activity in the brain, less oxygen is utilized, thus resulting in less oxidative damage. This principle is also used in cardiac bypasses, and is the reason for lowering the temperature of patients with cardiac arrest.

There are two IVs that go into the patient, each containing a different analgesic. In this surgery, propofol, a fast acting anesthesia, and another one I can't remember, are used. These are each connected to a bag of 0.9 sodium chloride solution. Another small bag of saline is also attached to the patient. This attachment actually involves a blood pressure gauge, and the saline is merely to prevent clotting. Also, if blood is required at any time during the surgery for testing, it is drawn via this tube. Antibiotics are also given to the patient during the surgery, although I am not sure why this is the case. The patient is also attached to a ventilator for respiratory function, where initial and final lung pressure, as well as the duration of inhalation, exhalation, and intervals can be determined. In this patient, the duration of inhalation is slightly shorter than that of exhalation. During the surgery, heart rate, pulse rate, blood pressure, blood oxygen content, and hematocrit is constantly monitored. Every so often, a blood sample is drawn to determine oxygen content, hematocrit, and ion levels, so that they can be adjusted if necessary. Some of the tests are redundant for an added layer of precaution in case one device fails to function. The hematocrit is regularly monitored because if it drops too low, blood transfusion is needed. The average hematocrit for a person is 45%, but a young healthy patient can withstand a level of 20%, while geriatric patients can withstand a level of 30%. These numbers are obviously approximate, because each patient is different. The goal is to avoid blood transfusions, because even though blood is tested before transfusion, there is still a risk of contracting HIV or hepatitis C (1 in 2,000,000 for both) or hepatitis B (1 in 205,000), or for an immune-compromised patient, the natural antibodies in the donor's blood may be too detrimental for the patient's own immune system to handle.

Week 2 - Rios

Now the second week of immersion has been concluded. A summer research project is now in place. It consists of setting up a flow chamber to study the effects of shear stress on corneal epithelial cells on a silk substrate. Already started on this and is positively moving forward. I expect to be done before the end of summer immersion. Also, I again had the opportunity to be present during the clinic days of Dr. Rosenblatt and Dr. Dematriades. I was able to observe through the teaching scope of the slit lamp. Lastly, I observed several refractive surgeries of two kinds. Photorefractive keratectomy (PRK) and Laser assisted in-situ keratomileusis (LASIK). In PRK, alcohol is used to loosen the epithelial layer of the cornea in order to remove it and have direct access to the stromal layer. Then a laser is used to ablate the stroma in order to reshape it and correct the vision. Finally, anti-inflammatory and anti-scarring medication is used and the epithelial layer will heal. On the other hand, in LASIK, a femtosecond laser is used to create a series of closely arranged bubbled underneath the epithelial layer of the cornea. Then, this layer, also called the flap, is pull back but it is still attached at a hinge point on one end. A different laser is used to ablate the stromal layer and correct the vision, and then the flap is put back into position creating a natural band-aid.

Week 2 - Stevenson T

This week I found out the importance of being able to use unexpected free time. With the INCREDIBLY busy schedules our mentors have, some meetings get postponed/cancelled, leaving you with several hours of unexpected free time in the hospital. With that in mind, early on this week I attended neurology rounds with James Lata. As I’m sure he has given a good description of this event, I’ll skip to the highlights.

Neurology Rounds - This is the first time I have been present during patient/physician interactions. I realized that health care providers must strike a careful balance when feeling empathy for their patients. On first glance I thought the attending physician and residents were being slightly callous, but with retrospection, I believe they were simply maintain a healthy psychological distance. This distancing may be of special importance in neurology, as roughly half of the cases we saw resulted in no intervention. “We can’t make the patient any better, so why subject him/her to a risky procedure that may severely reduce the quality of life?”

A more technical observation I made during rounds involved one elderly patient who had previously received a deep brain stimulator (DBS) for treatment of Parkinson’s Disease. While the technology/biology of the DBS is, for lack of a better word, cool, I took issue with some of the engineering that resulted in the patients re-hospitalization. The patient returned to the hospital after complications during a procedure to replace the battery on the DBS. This outcome seems completely unjustifiable with today’s current electronics technologya. Why would someone design a device that could only be accessed through very invasive surgery to have a “short” battery life? We can already walk into Best Buy and purchase a wireless power transducer that is capable of charging mobile devices, so why couldn’t we use a similar device to recharge the batteries of this DBS….

Citigroup Biological Imaging Center (CBIC)- Located on 72^nd street, the CBIC is where my mentor, Dr. Joseph Osborne, performs the majority of his clinical research. Though I had been to this building on several other occasions, I didn’t have the opportunity to speak with any of the technicians or observe any actual scanning procedures. This week I was able to see several.

microPET – on Tuesday, Dr. Osborne’s team was imaging a Rhesus monkey using a microPET scanning device. More specifically, they were measuring the binding/displacement of [¹¹C]-raclopride /dopamine. By getting a quantitative measure of the fraction of radiation in the animal’s brain, it is possible to determine the amount of raclopride vs. dopamine bound to D₂ dopamine receptors. This study was a preliminary control experiment that will be used to help study the effects of cocaine on the brain.

CT-PET – This scan was performed for a clinical trial of the Pittsburgh B compound, an amyloid plaque binding dye that can be modified to contain ¹¹C for PET scanning. What I found most interesting about this procedure was the need for an accurate X-ray CT prior to the PET scan. When PET photons travel through tissue, they get deflected/absorbed or otherwise attenuated by a factor that is roughly proportional to the density of the tissue. Thus one is able to generate a relatively low resolution CT scan of the body so that when the PET scan is taken, one is able to correct for attenuation on a voxel by voxel basis. The problem with this is that the scan/detector equipment for PET and CT are incompatible, requiring two scan zones to exist in the machine. After the patient receives a CT scan in the first region, the robotic table moves the patient into the PET scanning region. Though I’m sure the robotic mechanism for moving the patient is well calibrated, I wonder if it wouldn’t be simpler to redesign the electronics to have both sensors in the same scan area.

MRI – Before this week I never really considered an MRI machine to be a safety hazard. Sure, the magnetic field is quite strong and can be dangerous if you’re not aware of it, but you can plan for that and keep lots and lots of signs up warning people. What I’ve never before considered is the explosive force of the liquid cooling agents that are used to bring the machine down to superconducting temperatures. These liquids are usually N₂ and He (-80*C and -265*C respectively) and tent to expand approximately 700 times in volume when they become gases. Release of these gases would be more than enough to blow out the glass windows of a viewing room and displace a large portion of the oxygen in the air. This safety concern coupled with the need to constantly keep the machines on left me with a healthy respect for their destructive potential.

Project – I’m unfortunately still not entirely sure what my role in the project is going to be. I might be making the radiotracers in the hotlab or I may be reviewed patient data in an attempt to locate possible candidates. Either way, I will be working on a project to develop a small molecule PET tracer [¹⁸F] labeled, that will bind to PSMA and hopefully reveal any metastases that have escaped the prostate. Eventually this type of molecular imaging may be used for diagnostics or treatment, but currently, our goal is to better track the course of the disease.

Week 2 - Jawad

This week I got to see my first surgery, work on my project, and continued with the clinical rounds.

Monday and Tuesday were spent getting familiar with more details of the project. I learnt using DCMO, looked at T2-relaxometry in more detail. I went over several steps starting from extracting and organizing data from the MRI scans of patients ((de-identified, with patients consent), creating maps of the brain, applying masks to eliminate unwanted regions like skull and ears, etc. I would be working with T2-relaxometry performed at 3T, where the resulting data is very noisy. To appreciate it, I looked at comparative maps from T2-relaxometry at 1.5T and 3T.

Wednesday was spent with more work on T2-relaxometry. Here I looked at some code samples (in Matlab) which were used to implement several of the tasks toward noise reduction, and information extraction from T2-relaxometry-at-3T data. This was a great learning experience, as I got to appreciate how computationally expensive this all procedure was! It take 4 - 5 hours for the current algorithms to run to generate one 'image'. And we preferably would want to generate tens of them for one single patient. Imagining the amount of time required to do any comparative analysis on the data from a decent-sized (hundred or so?) sample of patients. I would hopefully get on to improving the algorithm in the coming weeks.

One thing that caught my attention (as mentioned by one of the postdocs) was the selection of certain parameters in the algorithm. The value for one such parameter was based on the resulting images as they appeared to the naked eye. While trained physicians, and people having some experience with these images of the brain may be able to tell which one is better, to me all the images at different value for the parameter were the same. I think a more objective criterion to establish the best value for the parameters is required.

Thursday I went to my first surgery. It was a laparoscopic, colorectal surgery performed by Dr. Lee. It didn't have anywhere near the kind of blood that I had in mind, yet I still felt dizzy and even went out of the OR for 10 minutes to get a hang of myself. Though it was suggested that I could look at the surgery from the small window in the door of the OR, I managed to pull myself back in. True to it's name, the incision was tiny. It was a case of colorectal cancer, and the patient was a female who was immuno-suppressed due to other medical conditions. It was fascinating to watch a surgery in real-time, and I could appreciate the experience of Dr. Lee and others who made it look easy! I was told by my fellows later that locating the tumor in such cases can be fairly challenging, however I think Dr. Lee and others took less than fifteen minutes in identifying the tumor!

Friday was spent shadowing Dr. Gauthier (my mentor) in her clinic. I saw one female senior citizen with a particularly aggressive case of multiple sclerosis (MS), and her inability to touch Dr. Gauthier's finger. I learnt about the current treatments (medications) for MS and their side-effects like burning and itching after Copaxen's injections and a risk of Progressive Multifocal Leukoencephalopathy (PML) with Tysabri.

I got to know that Biogen (the company that manufactures Tysabri) has come up with an antibody blood test for the JC virus that causes PML. And this test was offered free to the patients, and would be repeated once a year, so that the risks are known if a patient is to prescribed Tysabri. Currently the fatality risk of the patients that are JC-positive and are prescribed Tysabri is one in five hundred. Yikes!!

I am looking forward to seeing more surgeries, and hopefully go onto shadowing some other doctors in their clinical rounds next week.

Week 2 Plastics- Lindsey

This week started at 7am in the conference room on the 7th floor of Payson Pavillion. The guest surgeon, a former dentist and renowned plastic surgeon sought out by the wealthy and often previously botched patient, confirmed what I’d already suspected --- plastic surgery is one of the broadest , most complicated, intense and now sought after specialties in medicine.  “You will never be bored being a plastic surgeon,” he exclaimed, “ you can change your practice every 5 or so years.” And it’s true. Plastics surgeons do everything. You can focus on the more cosmetic kind of surgeries or trauma type surgeries.  You can pick what area of the body you’d like to focus on, if you’d like. Or can simply do it all. Monday’s conference focused on lip and chin surgeries. I learned that the mentalis muscle is a very important muscle in the face. It allows you to pout and close your mouth and must be carefully regarded in chin and lip surgeries. A plastic surgeon must pay very close attention to anatomy, so that when he is finished his surgery the patient may go about performing his everyday tasks as he did previously.  If a mentalis muscle is pushed too far down or severed, the patients won’t be able to play wind instruments, tell if they are dripping food from the lower part of their mouth or even put lipstick on without looking in the mirror.

The rest of the day and week were filled with patient visits and some really great surgeries.  After seeing the insertion of a tissue sizer and breast implants, I was really interested to see a TRAM flap. A TRAM, transverse rectus abdominus myocutaneous,  surgery was a breast reconstruction in which the post – mastectomy  breast was reconstructed from the tissue, fat and muscle of the abdomen , essentially providing the patient with a tummy tuck as well  as autologous breast reconstruction. The tissue from the abdomen was moved through a pedicle flap or tunnel up to chest to create the new breast. The nipple and areola would later be reconstructed in another surgery if the patient decided that was something she wanted. 

Another surgery I found really interesting was a jaw reconstruction after a tumor the size of three golf balls was removed from the patient’s jaw. This surgery began around 8am and lasted until 7:30pm. Oral and ENT were there in the morning removing the tumor from the patient’s jaw, while plastics simultaneously removed a portion of the patient’s fibula, as it is a non weight bearing portion of the leg, and could be used to recreate the patient’s jaw. The extraction of 16mm of the patient’s fibula along with the surrounding tissue skin and major blood supplies was a long delicate process. Doppler was used to mark the major vessels and the piece was extracted and then further cut to the specifications of the patient’s jaw. Prior to surgery a 3-D reconstruction of the patient’s jaw and tumor were made from CT images. A 3-D model was given to the surgeons and titanium constructs with multiple holes, where screws could be placed, were made to match the portion of the jaw that was being removed. These constructs were then used as a guide as to how the extracted fibula should be further sectioned.  The bones were then screwed onto the titanium constructs and the patient’s leg was sewn up and skin grafted. While a plastics fellow and resident worked on the closing of the patient’s leg, the attending and another resident moved up to the jaw where they sewed together the extracted blood vessels, attached to the skin, and tissue excised from the leg, to the severed blood vessels, left after oral removed the tumor. This was done under a scope with two eye pieces that allowed them both to work at the same time. The jaw was screwed in place and face closed up after flow was heard under the Doppler.  This was one of my favorite surgeries, as I’ve always studied soft tissue biomechanics and have never really been interest in orthopedics. I was really impressed by the technology and creativity used in this surgery. It opened my eyes to more areas of biomedical engineering that I might want to become involved with.

week 2 -- Joyce

I was recommended that laparoscopic colorectal surgery (minimally invasive surgery) is worth watching for beginners to warm up, because it is not so bloody and the disease locations could be zoomed on the monitors. I went to see Dr. Sang Lee’s minimally invasive surgeries on this Thursday. The first case is colorectal cancer of typical MINT surgery in that the 50 years old female patient is immune suppressive due to leukemia complication and MINT surgery is better to avoid further big infection than traditional abdomen incision. I was surprised to such a tiny hole they made in patient’s abdomen with a size just fitting the special fiber optic camera called laparoscopy. I did mouse experiments before and know how hard to localize intestinal tumors in so long GI track, even under dissecting microscopy. While laparoscopic surgery is hundreds times harder than mouse surgery, because the intestines in abdomen are rolled disorderly and all pink tissues / organs look so similar. Dr. Sang Lee and his assistants are very experienced and skillful and it took only ten minutes to spot the tumor sites. The probing speeds of camera Lens are so first that I felt dazzled with the changing internal images in the monitor.
The research goes slowly but progressively. Colon cancer primary culture is difficult in that enough driver colon cancer stem cells need to be harvested from human samples and immortalized in in vitro dish culture medium which takes a long time. The medium conditions and growth factors need to adjust to generate suitable in vitro growth environment. The original goal of my project is to culture colon cancer stem cells which are believed to be the cancer initiating cells retaining all the “driver” mutations and we use the serum free stem cell medium to purify the stem cell population since stem cell medium will keep stem cells in undifferentiated stage while the differentiated progenitor cells die up. It is much harder for primary colon cancer cells to survive in FBS free stem cell medium and the immortalization process usually takes longer. To guarantee we won’t lose the precious human cancer samples, I also implant the rest tumor tissues from primary culture in SCID mice for backup which serve as a good vector to sterilize the tumor tissues, retain human cell viability, purify and amplify the cancer cells.
One of the most interesting phenomena is that actually the human colon cancer tissues are heterogenous different from the single cell cloning conventional cell lines. After enzyme digestion, the deformed crypt structures were released out of the tumor tissues and they are formed by differentiated cancer cells. I think this is a proof of cancer stem cell concept, at least in intestinal tissues which are thought to be one of several organs retaining active adult stem cells in human body.
So far I succeed culture two primary colon cancer cell lines in stem cell medium and two primary cancer tissues grow out in mice which I will use for dish culture later.

Week 2 - Surgery Ahoy! ....Poornima

So, this week was all about seeing my first surgeries. Monday I got to spend time in the lab and observe the research being done in Dr. Schwartz’s lab. On Tuesday I saw 3 surgeries. One involved a Laminectomy and Discectomy. From what I understood the patient had a herniated disk stressing on the spine. As the patient was suffering from Cauda equina syndrome, the disk was not placed back into its original location. Rather, they made space by removing some of the bone to remove the stress. One could not observe much as it was a small incision on the back through which Dr. Schwartz and his resident worked through. The second surgery involved a tissue biopsy and was more interesting in terms of the instruments and technique applied. The patient had a tumor deep inside the brain that couldn’t be operated. 3 tissue samples were sent to the pathologist to determine wither the tumor is malignant or benign. The striking part was that the pathology report would take 2 days, as an engineer I found that a little disturbing. Most of these surgeries didn’t last more than 2 hours, but the next surgery was almost 6 hours long. It was a stereotaxic left craniotomy for an olfactory groove meningioma and was quite big. This surgery was my highlight of the week as I got to see a wide exposed skull, a craniotomy with cool drills and instruments where they removed a small part of the skull, dura, exposed brain and more and more. The whole surgery was displayed on a screen. It was a very bloody scene but surprisingly I found myself to be quite composed. The surgeons kept cauterizing the tissue as they went deep into the brain to stop bleeding. The tumor was finally removed at the end of 4 hours. Interestingly there was also an abnormal bone growth with this tumor which was drilled out and cauterized very carefully to remove every possible trace of the tumor.The energy, patience and focus of neurosurgeons is very remarkable, something to imbibe!

Wednesday, again was lab work for me as I assisted and observed a rat craniotomy for voltage sensitive dye imaging. And then Thursday turned exciting with 2 surgeries to watch. The first patient was suffering from Pituitary adenoma. The surgical technique was an endoscopic through-the-nose type. Initially a lumbar puncture was done to assess CSF’s biochemistry and pressure. CSF was further dyed with fluorsecin by injection to detect leaks. The whole surgery was displayed on two large screens and at one point we got to see a 3D version too. That was awesome. The surgeons went through the nose, removed some of the sphenoid sinus bone and dura, made incision and removed 3-4 large pea sized tumors. Here, the surgeons were worried of a possible CSF leak and placed a fat graft to prevent it. These tumors are generally easy to distinguish. The next surgery was a subdural hematoma. CT scan showed a lot of blood localized in the whole of the left hemisphere .It was incredible to see the dura expanded like a balloon by blood inside it, applying significant pressure on the brain. A large incision in the dura and flushing out the blood was all that took to get rid of the hematoma. Moreover, this time I got to see them leaving a tube on top of the dura to drain out any bleeding. Friday was again lab day for me and learnt about recording activity from the brain using voltage sensitive dye.

To sum up, this week was very eventful in comparison to last week and I can’t wait to see what comes in the next few weeks!

Week 2 - Sara

So this week, I got to see some surgeries. Dr. Nanus managed to set me up with urologists and they have kindly agreed to let me see their surgeries. On Monday, after a pain-staking hunt for scrubs and the schedule of my surgeon, I finally entered the OR for the first time of my life. Dr. Scherr had an emergency surgery. A tumor mass was found in the kidney of the female patient during a free screening. The tumor has grown into the vein and the heart. In the ultrasound in the OR, the tumor can be seen just entering the heart (which was amazing, but horrible at the same time). To remove the kidney, a cardiac-bypass is necessary to prevent the patient from bleeding to death after opening the vein. It was fascinating to see such a big surgery for my first surgery. The patient was literally open from the chest to the torso. The intestines were taken out for access to the kidney and renal vein. The chest was open for cardiac-bypass. I got to see the heart beating and how they did the stitches and attached the tubes to the pump. They also had to cool down the patient to stop metabolism since blood would only be circulating to the brain during the surgery. I saw the removed kidney with a tumor mass sticking out in the shape of the vein. I was told later that this was a very rare surgery and one of the most complicated surgeries in urology since it involves an urologist and cardiac surgeon. I must have been quite lucky to be able to watch this one.

On Wednesday, I got to watch two robotic prostectomy using da Vinci. This is as technologically-advanced as a surgery can get. A camera and various tools are inserted into the stomach of the patient via small openings for a minimally-invasive surgery, which allowed for better perservation of the blood vessels and nerves. The camera can zoom in 12x to improve the resolution and various tools are used to remove the prostate and to reattach the bladder to the uretery tract. The prostate, when removed, is actually placed in a bag, which is then sealed and removed from the body. The surgery was also shown on a 3D TV! This allows for the depth perception of the surgery, which definitely enhanced the experience.

On Friday, I went to a surgery with Brandon. It was interesting to go to surgeries in another department since most of the things I have done so far was in urology. It was definitely a worthwhile experience, and I will definitely branch out to other departments as well later in the immersion. Dr. Haytl, a neurological surgeon, was removing a tumor from C1 and C2 spine. The entire surgery required a lot of patience, experience and skill. The C1 and part of C2 were removed to access the tumor. It was very important not to cut the nerves, and to not damage the brain stem. The surgeons also only had a very small window from which they can remove and excise the tumor. An ultrasonic tool was also used to dissolve the tumor and aspirate it out. I was amazed at the patience of Dr. Haytl since the tumor was very persistent and difficult to be removed.

Tuesday and Thursdays are clinic days for Dr. Nanus and I followed him in his office. Surprisingly I am understanding more and can appreciate the cases a lot more. The days were also much less hectic that those in the first week, so Dr. Nanus has more time to explain the situation to me and I could ask more questions. Some very interesting cases came along. Dr. Nanus had a few new patients this week. One patient had found blood in her urine and her results were positive for cancer. It was heart-wrecking and difficult to watch as Dr. Nanus explained to her and her husband that she may or may not have cancer (more tests are required), but the chances are very high given her family history and her medical record (she had cancer previously). It was difficult to see how the patients are trying to minimize their emotions after receiving the news and approach the matter logically. I am amazed that doctors can do this regularly in their job as it was so painful for me to just stand there and listen to the conversation.

Another interesting case is that another patient has come in with a tumor mass in the kidney growing into the renal vein. He was referred to Dr. Scherr for surgery, which I hopefully will be able to observe. But, first, he must get an MRI in the brain to make sure he does not have metastases there, or else the surgery cannot take place.

As for the project, I am in the process of ordering antibodies and obtaining cell lines. Hopefully I can be trained on a flow cytometer soon, and get started!

James Week 2

6/20/2011 –

This morning I went into the normal room I usually do for rounds but was surprised to see all new faces. It turns out that every two weeks the team gets switched out and a new attending is in charge. I am now shadowing Dr. Jamieson and her team of neurologists, the only familiar face was the one resident Dr. Glass. I asked Dr. Glass about the whole switch and he said it is normal for the attending to be switched out, but usually the neurology team stays. Also, we have two brand new residents that shadowed with me today. Since there was a new attending the morning rounds were long getting her caught up on all the patients. We went through over 15 patients; normally we only go over 6 or 7. I learned that plavix is better to give than coumadin since it does not need to be routinely checked, and is just a lot easier. During morning report there were two cases that interested me. The first was a patient that they diagnosed with thalamic bleeding; on the images there was a massive hemorrhage, unknown origin but hypothesized to be at the thalamus. The next was a 5 year old suffering an intravenous hemorrhage, again it was fairly large. I then preceded to noon meeting which was on clinical trials for targeted therapies for MS. I finished my day in clinical with Dr. Leifer which went through many cases of unknown causes for symptoms (although I did not believe the symptoms were anything other than just getting older).

6/21/2011 –

The neurology team for rounds switched up again although it was still lead by Dr. Jamieson. The day went normal with rounds and morning report. The only case that was interesting was a patient that had self mutilation tendencies and was almost completely unresponsive during. During patient rounds we were told to stay clear of the patient, although a resident and the attending were trying to perform tests, it was kind of scary. The patient hit the resident and when they were strapping the patient back in the nurse said “watch out the patient bites!” This patient discouraged me from working with the mentally ill in general. After rounds I went to a neurology (stroke specific) conference. It was much like morning report, talking about the worst stroke patients of the week and explaining to the audience different ways to deal with each condition. The main thing I learned was the difference in clipping vs coiling an aneurism, overall coiling is better. The day ended with more clinical with Dr. Leifer.

6/22/2011 –

Dr. Leifer is out until Monday so I decided to contact some friends and watch my first neurosurgeries. I was apparently extremely lucky today because they were doing bilateral deep brain stimulation on a patient that was awake and cognitive. This surgery sent electrodes to the hypothalamus. The patient had “violent” tremors perhaps brought on by Parkinson’s. The stimulation is in a specific part of the brain (Can’t remember the exact word, it was SN something). The machine they utilized to judge positioning used auditory signals, which I thought was crude and very insensitive. I believe a Fourier transform on the electrical impulses detected would be a better read out. Once the electrode was in the correct position the next part was remarkable. They sent in small voltages 2-6 Volts and you could see the patient’s tremors completely stop. I spoke with the representative for the bilateral DBS and she said she has never seen such a successful surgery as this one. The next surgery was an endoscopic surgery on a morbidly obese patient who was being considered for a shunt. There was too much fat to find a good placement in the abdominal region so they decided to cancel the shunt.

6/23/2011-

Today I was surprised to find that the normal neurology team was switched, or so I thought. The new attending was Dr. Fink, and some of the team members I knew, so when I asked what happened they said they split the teams into two to handle 6 central and 2 west. I then went down to 2 west and met up with Dr. Jamieson and continued on rounds. I am now a part of the vascular neurology team. Rounds were very confusing, we are working with the vascular PA which likes to run away and we end up waiting. Also, things were just not well organized, it was very annoying.

6/24/2011 –

Rounds went better today, although still very disorganized. After morning report I decided to switch it up a little and followed Dr. Fink’s neurology team for his rounds. After rounds I met up with Dr. White who explained my research project to me. So, now I have a project, though I need to wait on paper work.

Week 2 - Joseph

Though last week my forays into the hospital immersion experience were primarily dominated by surgery, this week I broadened my approach to neurosurgery to include experiences with the diagnostic and research aspects of the field. On Monday and again on Thursday I went to clinical visits with my mentor, which was a very interesting, and very different, perspective on patient care. Whereas I had seen patients unconscious on the operating table for surgery and in the ICU when I attended rounds with neurology, in-office appointments were quite different.

These patients came in two varieties: the person who was wondering what was wrong, and the person who had been fixed. For the former, it was a mixed bag. Some cases were genuinely interesting, such as a man who was told that they had coincidentally found a hemangioblastoma that was occupying 80% of his spinal column. It was a miracle that he was not already quadriplegic, that his spinal cord was somehow still functional. I watched as Dr. Stieg explained that the man had a choice: wait a period of time (on the order of years) and become quadriplegic for certain, or get surgery now and hope that the decompression of the spinal cord from tumor removal did not cause just that anyway. As I would have expected, my mentor advised surgery, but honestly admitted it was a tough call. The difficulty was evident not only on the man’s face, but also on his daughter’s. She was just entering high school. And he was not the only one who faced a hard choice. A far younger man who had already undergone neurosurgery once before was shown a CT scan of a cavernous malformation sitting on the top of his brain stem. His choice was also interesting: he could have surgery, which carried a 5-10% risk of damaging the motor cortex slightly, or elect to leave it alone, which carried an 8% chance of bleed per year that would cause similar damage. My mentor noted that the defect was an absolutely perfect candidate for surgery, and that any possible (though statistically unlikely) damage as a result would only affect fine motor control. The twist? The man was just finishing graduate school as an artist. Again, Dr. Stieg suggested surgery, but again admitted it was not an easy choice. The man left undecided. I must admit I was moved by the difficulty of these choices. Previous encounters with neurosurgery were after the decision had been made; seeing the decision process added a new level of understanding for the complicated relationship between a patient and a surgeon.

But for every patient that had to face such a decision, there were three that were told there was nothing wrong with them. This might actually have been sadder to watch, actually. I watched young and old people alike, complaining of head pain that seemed to legitimately be causing them severe pain and stress (sometimes pre-op, sometimes post-), be told that there was simply nothing wrong from a surgical perspective, and they would have to search elsewhere for answers and treatment. The trouble was no one comes to neurosurgery first, it’s always down the line as you get increasingly desperate and worried. Being told that there was nothing a neurosurgeon could do to help seemed particularly depressing to many, despite the fact that it often contained assurance that they were not going to drop dead in the street tomorrow (because that would definitely show up on the MRI!).

All that being said, I mostly enjoyed the latter flavor of cases, the regular check-ups with patients who had had surgery done by Dr. Stieg at some point in the past. They were almost exclusively older, nice people who had developed a relationship with my mentor over years of post-op visits, and they were all happy to see him and happy to hear all was still well with their brains. Some even brought home-cooked food as a continuing sign of thanks for all he had done for them. My wife (a student in veterinary school also at Cornell) always tells me that they constantly drill into young medical students that the ability to develop a rapport with your patients is as important as being able to treat them. It was clear that Dr. Stieg was a master at doing just that, and as a credit to him, it clearly made him a better doctor.

I also attended my first weekly neurosurgery conference on Monday, which I am happy to report demonstrated that at least one stereotype about surgeons is not true: surgeons CAN be talked out of surgery! To back up a bit, a conference is where doctors meet to discuss their patients’ cases and ask for input and consensus concerning treatment. This particular conference was of course primarily neurosurgeons, but also included radiologists and neurologists who lent their own less surgically focused opinions to discussions of difficult cases. I was surprised at how often everyone agreed on when an aneurysm was too difficult to treat, as was the case with one woman who had a basilar fusiform aneurysm which everyone agreed quite readily as being simply too risky to clip or coil. Tumors and cysts of various sizes and positions were also discussed, each time lead by a re-diagnosis by the radiologist, a suggestion by the neurologist, and a discussion by all present. It was... well, let’s say reassuring to see that doctors are willing to seek input from their peers before assuming they simply by default know best and take a drill to your skull.

As Dr. Frayer would say, I also continued to “collect surgeries” – another meningioma removal (this one fully intact, actually; it resembled a walnut), a couple ventriculoperitoneal shunt placements for treatment of hydrocephalus. I made an effort to seek out surgeries that were different from what I had seen last week. The most interesting surgery I saw was bilateral deep brain stimulation done on an awake patient for insertion of electrodes as a treatment for his Parkinson’s disease. It was easily the most delicate and technically complex surgery I have witnessed to date. To summarize the spectacle, the goal was to place electrodes in the subthalamic nuclei (SNT), a motor region underneath the hypothalamus relatively deep within the brain, for constant delivery of electrical current that would suppress the man’s constant tremors, which were easily visible underneath the blanket covering him for surgery. A trajectory was determined by aligning a brain CT taken right before the surgery with real-time X-rays done on the table, following which holes were carefully drilled in the skull. It was honestly a completely different surgical procedure compared to the rapidity I’d seen in the past for cranial entry… probably had something to do with, you know, the actually awake status of the patient. A rather bulky apparatus that resembled a giant protractor allowed precise adjustment and calibration of the insertion trajectory, the completion of which was followed by careful insertion of the electrodes themselves. Now this was legitimately a feat of biomedical engineering to behold, as the electrode insertion device could pick up the electrochemical activity of the cells it passed through, which, with a combination of signal processing and a good ear, allowed the surgeon (Dr. Kaplitt) to determine when he had reached not just the SNT, but the exact position in the three-dimensional space that was most ideal for stimulation. And he hit it perfectly on both approaches, which the on-site vendor for the device confessed to me hardly ever happens, indicating Dr. Kaplitt was very, very good at what he does. This is where the patient played a role, too, as the specific sounds they were searching for were generated by him flexing and relaxing various appendages in rapid succession. But the truly magical part of the surgery was watching them connect the electrodes to a voltage source, turn it on, and then watching the tremors gradually and completely stop as the voltage was increased and optimized. As if having your brain open while conscious wasn’t shocking enough in general, you honestly should have seen the look on the man’s face when he lifted his hand in front of his face and noted with amazement that it was not shaking. Upon further conversation with the vendor I learned that at an appropriate time after the surgery, the exact electrical stimulation would be calibrated using variable voltage, pulsewidth, and frequency optimization to maximize tremor reduction while minimizing any neurological defect. The mechanical programming of a global neuron response of such magnitude, to this humble biomedical engineer at least, was truly a feat to behold indeed.

Friday proved to be what I am going to begin referring to as my “graduate student day”. With my mentor out of town, I worked both on my medical research project (which currently is vacillating between a project focusing on ultrasound disruption of the blood brain barrier for drug delivery applications and a completely unrelated viral vector gene delivery project) as well as on my thesis project back home (which, as my thesis advisor is keen to remind me from time to time, I should be writing a paper on). It was actually a fun reminder of why I enjoy being a PhD student – reading papers, brainstorming ideas, familiarizing myself with protocols, and regularly transitioning between very diverse topics to keep my focus sharp (for the record, the paper I’m writing for journal submission is on nanobiotechnology applications for vaccine delivery, so… again, completely unrelated). I have a meeting with Dr. Stieg’s collaborator on Monday (the Dr. Kaplitt mentioned above, incidentally) to finalize project ideas, at which point it seems likely I’ll be heading for some lab work on top of clinical and OR immersion. And here I thought I opted out of the MD-PhD path!

As a concluding note, the patient I mentioned in my last post who had not yet woken up following her traumatic incident on the operating table gained full consciousness on Monday (five days after the surgery). When last I checked in, they were still gradually assessing her cognitive function. Dr. Frayer suggested that it was a good thing to follow patient cases like this, so here’s hoping for a full recovery by next week.