Human Anatomy at Colby

Ariel Oppong, Jay Lee, Rebecca Gray

http://youtu.be/_0jV_CS7gXo

Grand Rounds _Hyperplasia powerpoint pdf

Grand Rounds Synopsis- Atypical Hyperplasia of the Breast

Hyperplasia occurs when an organ or tissue becomes enlarged because the cells within it begin to proliferate more quickly than usual, resulting in an abnormally large population of cells in one, concentrated area of the body. We categorize hyperplasia in two ways: (1) “simple” or “complex”, and (2) “usual” or “atypical”. The research we will explore focuses on complex, atypical hyperplasia. This refers to hyperplastic tissue that both engorges the tissue around it and contains deformed, non-uniform cells.

Hyperplasia of the breast falls into two categories: lobular and ductal. Within the fatty tissue of a healthy breast are mammary glands, and within those lie lobular clusters of alveoli. The cuboidal cells that line these alveoli secrete milk, which moves through milk ducts to reach the nipple, where it is excreted during breastfeeding. When hyperplasia occurs in the breast, it is usually found in either the lobules of the mammary gland or the associated milk ducts.

Usually, hyperplasia within the breast is relatively harmless. Because change in breast size and shape occurs normally over the course of a woman’s life, her body is designed to handle minor engorgement of the tissue there. This condition becomes concerning when hyperplastic cells within the breast become atypical; this is characterized by misshapen cytosol, nuclei, and membrane organization. When this occurs, the hyperplastic cells take on characteristics startlingly similar to those of tumors: they are clumped, proliferating rapidly, and lacking functionality. For this reason, atypical hyperplasia of the breast is linked with breast cancer and considered premalignant.

Usually if a lump or an abnormal mass is found during a female’s mammogram then a health professional will usually suggest a biopsy. During the biopsy tissue cells are removed for analysis by a pathologist.  If the pathologist can not make a definite decision as to if the excision is cancerous or not.

A 2014 report published by the New England Journal of Medicine published a new meta-analysis of the associated risk of breast cancer associated with atypical hyperplasia. The conclusions of the meta-analysis suggested that a women with a atypical hyperplasia has a least a 30% increased risk of having breast cancer within a 25 year follow-up. Due to this new information we ( the anatomy group) as well as the authors of this newly published report agree that there needs to be a reform in women’s health policies so that women are more aware of their risk and are also more informed about some preventative medicine including screening techniques, and treatment or surgical options if signs of breast cancer are already apparent.

Some of the current commonly used treatments are different types of SERMS. SERMS are selective estrogen receptor modulators. The most widely used antiestrogen for management of breast cancer is Tamoxifen. However, prolonged use of Tamoxifen does increase one’s risk for endometrial (uterine) cancer.

Another important issue is the health disparities in breast cancer diagnosis, quality of treatment, and mortality rates among different socio-economic groups, geographic locations, the unemployed and employed, and racial groups. Based of off data from the 2014 Racial Disparity in Breast Cancer Mortality Study in areas such as Memphis, Tennessee, black women are more than two times more likely to die of breast cancer than their white counterparts. Overall, our research indicates that we as a country need to implement new screening methods, need to promote more education initiatives, need to enact new policies to decrease health disparities, and need to stress the powerful conclusions that meta-analysis provide.

Grand Rounds: Oligoastrocytoma

Alex Lucas, Yvette Qu, Rachel Bird

http://youtu.be/wguUeUNttac

Grand Rounds_Oligoastrocytoma_powerpoint pdf

Oligoastrocytoma

Oligoastrocytomas are brain tumors that consist of oligodendrocytes and astrocytes, the two cell types in the brain that support and insulate nerve cells. Unlike many brain tumors, which typically present initially with headaches, seizures are a common initial symptom of oligoastrocytomas.

The patient presented with episodes of “a feeling of walking through a cloud,” receptive, or Wernicke’s aphasia (the inability to understand spoken words), Aphasia (inability to speak), and vertigo. She also suffered from brief seizures, which worsened in severity over the course of the next eight years, and began to involve loss of consciousness and muscle tone, occasional incontinence, and overwhelming confusion. Three months prior to admittance, the patient struck her head during an episode, but MRI, ECG, echocardiography, Holter monitoring, EEG and multiple blood tests all appeared normal. The patient did not respond to triptans or beta-blockers, but the frequency of her seizures increased to at least one per day.

An MRI was performed on the patient, which showed a mass in the left occipitotemporal region of the brain. A biopsy helped to determine the grade of the tumor – grade II, which is a low grade tumor – and also presents the pathology which helps to determine the growth patterns of the tumor cells. Fluorescence in situ hybridization (FISH), which allows for reliable and accurate detection of chromosomal deletions, showed deletions in 1p and 19q tumors.

Similar to most tumors, the exact cause of an oligoastrocytoma is unknown. It is understood that normal cells become abnormal in the sense that they may produce the wrong number of proteins or enzymes or be lacking certain genetic material. In the case of an oligoastrocytoma, deletions of genetic information in chromosomes 1p and 19q are the reason for the tumor cell’s abnormalities. This certain type of tumor is a result of a mixture of oligodendrocytes and astrocytes. Genetic material losses in 19q occur in 60-80% of oligodendrogliomas and 30-40% in astrocytomas, which demonstrate that there may be a shared variation in the formation of gliomas. Losses in the 1p chromosome are frequent with oligodendrogliomas at about 50-80%, however are less apparent with astrocytomas, which is detected only 10-18% of the time. However, the combination of genetic material losses of the 1p and 19q chromosomes is detected in 60-80% of oligoastrocytoma cases.

A gross resection was performed to remove the patient’s low-grade oligoastrocytoma tumor. Standard radiotherapy and antiepileptic medications were given after the resection. Lifelong MRI was suggested instead of permanent pacemaker due to the low-grade of the tumor. Following MRI shows only postsurgical changes, implying good prognosis. During the 24-month following the resection, no seizure has occurred with reduction in medication, indicating great possibility of freedom from seizure in 10 years and absence of intractability.

The patient’s case is complicated by ictal asystole (stopping of the heart during her epileptic seizures, which is very rare) in a patient with a predisposition to neurocardiogenic syncope (fainting, loss of consciousness, loss of muscle tone due to an abnormal control mechanism of the brain over the heart) due to a genetic disorder, and with the asystole being triggered by the seizures caused by her oligoastrocytoma make this case very interesting and unique. The important information the case conveys is that a patient’s symptoms are not always indications of a single disease, and sometimes the symptoms need to be closely examined and can suggest more than one disease. Perhaps screening for relationships between cardiac dysfunction and neurologic mechanisms could help identify rare cases such as this one, which would allow for earlier diagnosis and treatment.

References:

(1) Paleologos, N A, ed. Oligodendroglioma and Oligoastrocytoma. Am Br Tum Assoc 2014: 3-8.

(2) Oligoastrocytoma. Univ CO Sch of Med Neusrgy 2015.

(3) Meenakshi G, MD, Azita Djalilvand, MD, Daniel J. Brat, MD, PhD. Clarifying the Diffuse Gliomas. Am J Clin Pathol. 2005;124(5):755-768.

(4) Cole, AJ, M.D., Eskandar, E. M.D., Mela, T, M.D., Noebels, J.L. M.D., Ph.D., Gonzalez, R.G. M.D., Ph.D., McGuone, D, M.B., Ch.B. Case 18-2013 — A 32-Year-Old Woman with Recurrent Episodes of Altered Consciousness. N Engl J Med 2013; 368:2304-2312.

(5) Ucdenver.edu. Department of Neurosurgery [Internet]. 2015 [cited 2015 Jan 15]; Available from:http://www.ucdenver.edu/academics/colleges/medicalschool/departments/Neurosurgery/patientcare/multi-disciplinaryprograms/AdultBrainTumorProgram/Pages/Oligoastrocytoma.aspx

Lauren Shirley, Allison O’Connor, Cal Robbins

Grand Rounds Synopsis

Case 28-2010 A 32-Year-Old, 3 Weeks Postpartum with Substernal Chest Pain

http://youtu.be/bODWv-x-eDc

Grand Rounds Case Presentation powerpoint pdf

Onset

A 32-year old woman had an uncomplicated, spontaneous vaginal delivery after 39 weeks of gestation. This was the patient’s second pregnancy. During her first pregnancy, she was diagnosed with preeclamptic toxemia which was treated with magnesium sulfate. Mild hypertension (systolic 120-140 mm Hg) was reported during the first and third trimesters of her second pregnancy followed by a return to normal blood pressure. Upon delivery, it was noted that her placenta weighed 340 g (below the fifth percentile for gestational age, mean 540 g) with increased amounts of perivillous fibrin (suggesting placental ischemia- lack of blood and thus oxygen and glucose to tissue).

The patient was admitted three weeks post partum when she developed pain in the left jaw and substernal area. The patient called EMS and was given oxygen which resolved her symptoms after 20 minutes and EMS personnel left. The pain returned shortly and EMS returned whereupon the pt scored her pain as a 7 out of 10. Blood pressure was noted as 148/74 and an electrocardiogram (ECG) revealed normal sinus rhythm of 90-100 bpm and ST-segment elevation of 4 mm in leads V2 and V3 (Abnormalities in ECG). Oxygen, acetyl-salicylic acid, nitroglycerin and morphine were administered. When examined at the hospital, the pt’s blood pressure was 143/92 mm Hg in her left arm and 137/81 mm Hg in her right arm with a pulse of 83-92 bpm.

Diagnosis

With a chief complaint of chest pain the patient could have been experiencing cardiovascular, pulmonary, gastrointestinal or musculoskeletal complications. Since the patient was 32 years old, cardiovascular complications would seem unlikely, however, since the patient was three weeks postpartum cardiovascular complications need to be considered more carefully since the risk of acute myocardial infarction is increased during pregnancy and the postpartum period and since pregnancy is a risk factor for aortic dissection. The risk of pulmonary embolism (a blockage of an artery in the lungs) is also increased during the postpartum period.

Since the patient’s ECG showed ST-segment elevation in conjunction with chest pain, an acute myocardial infarction would be suspected. Approximately 35% of postpartum women who present with myocardial infarction have a coronary artery dissection. There are two main types of coronary artery dissections, those that are caused by mechanical precipitation and those that are spontaneous. A spontaneous dissection is a tear in the artery where the tunica media and tunica externa separate, allowing blood to pool in between these layers. SCAD are rare, however 75% of patients who present with spontaneous aortic dissections are women and 30%  of those women are peripartum, suggesting that this patient’s coronary artery dissection was spontaneous. There are four subgroups of spontaneous coronary artery dissections, however peripartum status and idiopathic spontaneous coronary-artery dissections or those caused by coronary shear stress are the two subgroups relevant to this case. Since the chest pain began after the patient picked up her toddler, there is a high index of suspicion that this dissection may have been caused by the patient’s peripartum status and coronary shear stress caused by lifting her toddler. Angiographic projections showed 35mm long segment of narrowing in the left anterior descending coronary artery.  The lack of vascular disease in other coronary arteries along with the patient’s postpartum status as well as her test results are consistent with the diagnosis of a postpartum coronary-artery dissection.

Treatment Options

Unlike aortic dissections, the usual chest pain drugs (asprin, nitroglycerin, etc) which thin the blood can actually help, keeping the true lamen patent. Beta-blockers and nitrates are often used to prevent superimposed vapospasm.  In cases of myocardial ischemia or compromised coronary flow, reperfusion therapy is used.  In patients with severe ischemia, coronary-artery bypass  grafting is done. In this case, the patient was given an intra aortic balloon pump which helps to increase myocardial oxygen supply by being placed in the aorta where it inflates and decreases based on the heart beat.  Since the patient had no pain and the Percutaneous Coronary Intervention could have entered the false lumen, and since coronary dissections can heal by themselves, the balloon pump makes the most sense.  This increased blood flow to the coronary artery.  Aspirin as an antiplatelet, ß-blockers, and statins were used in case of intramural hematoma in the coronary vessel.  Because of the potential for emergency cardiac surgery, the patient was not given glycoprotein IIb/IIIa inhibitors.

After 2 days a significant improvement was noted, the pump was terminated, and since surgery was now unlikely, glycoprotein inhibitors were initiated  for a minor myocardial infarction discovered during treatment of the aortic dissection. This would be discontinued in a year, while aspirin was recommended indefinitely. The patient was able to return to her normal life with no further complications.

Little evidence exist in terms of the cause of spontaneous coronary artery dissections, but the current theory is that  inflammation is caused by hormones, which explains the prevalence in post partum women.  Several studies also included women taking oral contraceptives as being at risk for coronary artery dissections.  The eosinophils release the histolytic agents between the tunica media and the tunica adventitia, which cause dissections in coronary arteries.

References

1. Sabatine, Marc S., Farouc A. Jaffer, Paul N. Statts, and James R. Stone. “Case 28-2010: A 32-Year-Old Woman, 3 Weeks Post Partum, with Substernal Chest Pain.”The New England Journal of Medicine (2010): n. pag. Web.
2. James, A. H. “Acute Myocardial Infarction in Pregnancy: A United States Population-Based Study.” Circulation 113.12 (2006): 1564-571. Web.
3. Koul, Ashok K., Gerald Hollander, Norbert Moskovits, Robert Frankel, Leo Herrera, and Jacob Shani. “Coronary Artery Dissection during Pregnancy and the Postpartum Period: Two Case Reports and Review of Literature.” Catheterization and Cardiovascular Interventions 52.1 (2001): 88-94. Web.
4. Mcintyre-Spatar, Leslie, and Kevin H. Silver. “Spontaneous Coronary Artery Dissection in a Postpartum Woman: Literature Review.” The Journal for Nurse Practitioners 7.9 (2011): 770-73.
5. Oliveira Marta Silvia, Goncalves Alexandra, Dias Paula, Maciel Júlia Maria. “Spontaneous Coronary Artery Dissection: a Diagnosis to consider in Acute Coronary Artery Syndromes” Artigos de Revisão. (2009): 28 (6): 707-713
6. Heart Assist Devices. Texas Heart Institute, 2015. (Accessed January 20, 2015 at http://www.texasheart.org/Research/Devices/iabp.cfm)
7. CBC. MedlinePlus, 2015. (Accessed Janury 25, 2015 at http://www.nlm.nih.gov/medlineplus/ency/article/003642.htm)
8. Placental Pathology. University of Chicago. (Accessed January 20, 2015 at https://pathology.uchicago.edu/sites/pathology.uchicago.edu/files/uploads/PDFs/Placental%20Pathology%20Notes%20Aspen%202014%20-Fritsch%20final.pdf)
9. Electrolytes. AACC, 2013. (Accessed January 25, 2015 at http://labtestsonline.org/understanding/analytes/electrolytes/tab/test/)
10. CK-MB. AACC, 2013. (Accessed January 25, 2015 at http://labtestsonline.org/understanding/analytes/ckmb/tab/sample/)

CABG vs. Stenting in Multi-vessel Procedures: A Synopsis

Mayra Arroyo, Chris Lee, Ivan Yang

http://youtu.be/xsxlDjFb_sk

Coronary artery disease is caused by atherosclerosis, or the accumulation of fatty deposits, known as plaque, along the innermost layer of the coronary arteries. There are three main coronary arteries: the right coronary artery, circumflex artery, and the left anterior descending artery.  Atherosclerosis causes the afflicted coronary artery’s wall to thicken and lose elasticity, ultimately narrowing or blocking the artery. This can reduce the oxygen flow to the myocardium. Treatment of coronary artery disease is complex and depends on several factors, but typically comprises of risk factor management, medication, and interventional techniques, such as coronary artery bypass grafting (CABG) and stenting.

Percutaneous Coronary Intervention (PCI) or Stenting is a minimally invasive process in which a doctor inflates a stent (mesh steel tube) with a balloon to open up a clogged artery. This restores normal blood flow. A catheter is inserted through the groin, neck, or arm to move the stent to the affected area.  In recent years, newer types of stents such as drug-eluting stents and biodegradable ones have been developed. Before choosing stenting as a treatment option, one should consider risks involved with stenting such as damage to the vessels or arteries.

CABG is a surgical procedure where a vein or artery (usually from the inner thigh) is used to form a path around a blocked coronary artery. Over the years, there have been changes to the techniques used to carry out CABG. One such example is Totally Endoscopic CABG, which uses a robot equipped with a camera and surgical instruments in its arms. It is important to note that this procedure is highly invasive and risky, which is why it is usually used after more conservative treatments have been attempted.

In the three studies discussed, we compared long-term outcomes of CABG and stenting in multi-vessel disease in diabetics and in combined subgroups by looking at death rates, adverse event rates, and repeat revascularization rates.  Multi-vessel disease is defined as the occlusion of two or more of the three main coronary arteries, and revascularization is a procedure that returns blood flow to a low-oxygen area.

In diabetics, we found that CABG ultimately has better long-term outcomes in multi-vessel treatment.  Primary outcome (death, heart attack, or stroke) rates and all-cause mortality rates were lower in CABG diabetic patients than in diabetic patients who underwent drug-eluting stent procedures.

A study published in 2001 observed the effects that CABG and stent had on patients one year after treatment. The patients’ quality of life (survival and freedom from stroke, heart attack, or repeat revascularization) was examined after one year. It was found that there were no significant differences between the number of CABG and stent patients who did not die or have heart attacks or strokes. However, CABG patients had lower rates of repeat revascularizations than stent patients. In light of this study, it is important to remember that it was conducted in a time before drug-eluting stents and other newer treatment options.

Another study published in January of 2013 found that, compared to CABG patients, a greater percentage of people who underwent PCI with drug-eluting stents underwent repeat revascularization. The study concluded that in people with less complex disease, it is acceptable to undergo PCI. On the other hand, people with multi-vessel problems should choose CABG.

In conclusion, though CABG has proven to have better long-term outcomes than stenting in multi-vessel disease treatment, better studies should be conducted to verify this.   Future studies should include more patients, cover modern CABG and stent techniques, and be extended for several years after revascularization.  For now, it appears that CABG does have an advantage over stenting and drug-eluting stents, mostly due to reduced rates of repeat revascularization.

Ari Thomas, Laurel Edington and Danielle Levine

http://youtu.be/DiKDOyG6Olg

Grand_Rounds_Celiac_Disease powerpoint_pdf

Grand Rounds Synopsis

A 42-year-old man presented with a chief complaint of chest and abdominal discomfort that had begun suddenly two days before as a sharp left upper quadrant pain radiating to his back, associated with nausea and early satiety, and that increased in intensity over the next two days. The next day, he experienced substernal chest pressure consistent with his usual angina, but which did not respond to a single sublingual nitroglycerin tablet; it only resolved completely after IV morphine, ketorolac (an NSAID), chewable aspirin, and three more sublingual nitroglycerin tablets. He had experienced no recent abdominal trauma, vomiting, rectal bleeding or black stools.¹

The patient’s past medical history includes hypertension, hyperlipidemia (excess blood lipids), and coronary artery disease (myocardial infarction at 32 years of age, with coronary artery angioplasty with stent placement, and subsequent bypass grafting).^1,2 For more than ten years before presentation (since the coronary-artery bypass surgery), he has experienced chronic diarrhea that has worsened since his cholesterol-lowering medication was increased 6 months ago.¹  During the past six months, he has experienced daily headaches, nocturia (excessive urination at night), feeling warm at night, an unintentional weight loss of 35 lbs, and occasional early satiety.^1,2  Although he has a family history of colon cancer, a colonoscopy performed 4 months prior was unremarkable.¹

The abdominal and chest pain, weight loss, and history of gastrointestinal symptoms suggested an acute chest syndrome, acute abdominal syndrome, inflammatory disorder, or cancer. An acute coronary syndrome was unlikely and an echocardiogram and chest radiography confirmed this. The physical exam ruled out acute chest syndromes, but sensitivity in the upper right quadrant suggested an upper abdominal disorder. Lipase, aminotransferase, and amylase levels were elevated, suggesting pancreatitis, liver injury (from an infection or drug use) or disease, or liver cancer. A CT scan of the abdomen ruled out pancreatitis and colon and small bowel disorders, but showed enlarged jejunal lymph nodes. An exploratory laparotomy was performed and the lymph nodes showed reactive follicular and interfollicular hyperplasia and lipogranulomas, suggesting an inflammatory abdominal disorder. Evidence of lymphoproliferative disorders was absent, ruling out cancer. A small-bowel biopsy showed flattened villi and intraepithelial lymphocytes, which suggested celiac disease. Positive IgA tissue transglutaminas and IgA endomysial antibody tests, the most specific and sensitive tests for celiac disease, were positive and confirmed the final diagnosis.¹

The patient was advised to follow a gluten-free diet with an intramuscular iron supplementation as well as a multivitamin for general vitamin and mineral deficiencies.³ The gluten-free diet includes avoiding foods made out of wheat, rye, barley, oats, and processed foods that may contain wheat flour.⁴

Based on the patient’s symptoms, doctors diagnosed the patient with celiac disease. This disease is an autoimmune disorder that is provoked by intaking various forms of gluten and affects the small bowel. The intestinal symptoms of this disease include abdominal pain, diarrhea, a mild elevation of aminotransferase levels, and an increased risk of pancreatitis. Abdominal pain in the patient may have been due to transient intussusception related to celiac enteropathy.  Celiac disease also has extragastrointestinal system effects such as rashes, arthralgias, neurologic and psychiatric effects, fatigue, and infertility.⁴ Patients also suffer from malabsorption of nutrients which can lead to weight loss, iron-deficiency, and osteoporosis. Patients have an abnormal immune response to the gliadin component of the gluten protein, where type 1 helper T cells cause inflammation in the epithelium and lamina propria of the small intestine, which alters the structures of the intestinal villi and therefore causes malabsorption.³ Celiac disease may also accompany type 1 diabetes, thyroiditis, and hepatitis.¹

Celiac disease is different than a gluten sensitivity.⁵ Although the symptoms are similar, a person with a gluten sensitivity does not have the intestinal damage that a person with celiac disease has. Patients with a gluten sensitivity also do not have the IgA tissue transglutaminase or IgA endomysial antibodies that patients with celiac disease have.⁶ Since blood tests and intestinal biopsies will not diagnose a gluten sensitivity, using a process of exclusion helps to diagnose the sensitivity.⁵ Both disorders are treated by following a strict gluten-free diet.^5,6

References:

1. Ole-Petter Riksfjord Hamnvik, M.D., Fidencio Saldana, M.D., Bruce D. Levy, M.D., and Joseph Loscalzo, M.D., Ph.D. N Engl J Med 2014; 371:1333-1338.

2. Medline Plus: Medical Dictionary. Besthesda, MD: U.S. National Library of Medicine, 2012. (Accessed January 13, 2015 at http://www.nlm.nih.gov/medlineplus/mplusdictionary.html.)

3. Leffler, D. Celiac Disease Diagnosis and Management: A 46-Year-Old Woman With Anemia. Jama 2011; 306:1582–1592.

4. Rubio-Tapia, A., Hill, I. D., Kelly, C. P., Calderwood, A. H., & Murray, J. A. American College of Gastroenterology Clinical Guideline: Diagnosis and Management of Celiac Disease. The American Journal of Gastroenterology 2013, 108:656–677.

5. Non-Celiac Gluten Sensitivity.  Ambler, PA.: National Foundation for Celiac Awareness, 2015. (Accessed January 25, at http://www.celiaccentral.org/non-celiac-gluten-sensitivity/).

6. Gluten Sensitivity.  Woodland Hills, CA.: Celiac Disease Foundation, 2015.  (Accessed January 25, at http://celiac.org/celiac-disease/non-celiac-gluten-sensitivity/).