SURGERY CASE

A 57/female consulted at the OPD with a chief complaint of melena

History of Present Illness:

 8 months prior to consultation, a 57-year-old female started to have intermittent melena for a total of 5
episodes which she ignored. However, 1 day prior to consultation, she had another episode of melena.
Patient was then admitted for work up and findings were noted:

PE:    
    BP: 120/90 mmHg
    RR: 18cpm
    PR: 100 bpm
    Afebrile
    BMI: 20 kg/m2
    Unremarkable except for pale palpebral conjunctiva
    Soft abdomen; (+) palpable epigastric mass
    DRE: unremarkable; (-) blood per examining finger

LABS:
All laboratory work-up were normal except for the Hgb: 80mg/dl

UPPER GI ENDOSCOPY: 
Esophageal mucosa is smooth and shiny. The stomach is normally dilated. The pylorus and duodenum
were unremarkable. There was an ulcer seen in the upper body of the lesser curvature with bulging
mucosa but no active bleeding.  Gastric folds were intact except in the area surrounding the ulcer. Biopsy
was done.
Impression: gastric ulcer, upper body.

CT scan: a 5x4cm intraperitoneal mass seen in the upper abdomen, ventrally placed and sharply
demarcated from the surrounding structures except from the lesser curvature of the stomach. No
lymphadenopathies noted. 

The UGI Endoscopy biopsy result was: Spindle cell tumor with chronic inflammation; AND
IMMUNOHISTOCHEMISTRY STAINING DONE: CD117 (+); DOG1 (+); cytokeratin (-); desmin (-).
She was  then scheduled for an exploratory laparotomy, wedge resection of the lesser curvature and
sample sent for permanent histopathologic examination.  The surgery was unremarkable and she was sent
home 7th post-operative day and was followed up at the out-patient department. The final histopathology
report showed GASTROINTESTINAL STROMAL TUMOR 5.5 CM; margins negative; high mitotic
rate. 

Assumption: The student understands the anatomy (including blood supply) and physiology of the
gastrointestinal tract, to include the esophagus, stomach, small bowel, colon, and anorectum. 

Goal: The student will be able to describe the initial management of a patient with acute upper and lower
GI hemorrhage. The student will be able to name the major causes of GI hemorrhage and develop a
diagnostic and treatment plan for each.
LEARNING OBJECTIVES:

1. What further data should be obtained from the patient’s history?

 A detailed review of current medications should be performed, and patients should be directly
asked about the use of NSAIDs, antiplatelet drugs, aspirin, or anticoagulants. Also, it is important
to get a detailed social history regarding alcohol use.

 Key details in the history should include whether the bleeding is recurrent or sporadic if there are
associated symptoms and a detailed review of the patient's medications including, antiplatelets,
anticoagulants, and NSAIDs. The family history of colon cancer or inflammatory bowel disease
(IBD) should also be noted. 

2. What physical exam findings would you look for? 

 For the physical examination findings, the presence of abdominal pain, especially if severe and
associated with rebound tenderness or involuntary guarding, raises concern for perforation. If any
signs of an acute abdomen are present, further evaluation to exclude a perforation is required
prior to endoscopy. Examination of  the stool color may provide a clue to the location of the
bleeding. 

3. What is your differential diagnosis? 

 The differential diagnosis of a subepithelial tumor arising in the gastrointestinal tract is broad and
can include GIST, leiomyosarcoma, leiomyoma, malignant melanoma, schwannoma, malignant
peripheral nerve sheath tumor, fibromatosis (desmoid tumor), inflammatory myofibroblastic
tumor, or even metaplastic ("sarcomatoid") carcinoma. 

 By light microscopy alone, the distinction among GISTs and other tumors in the differential
diagnosis (particularly leiomyomas, true leiomyosarcomas, and gastrointestinal tract
schwannomas) can be difficult because the histologic findings seen on hematoxylin and eosin
(H&E)-stained sections do not reliably or specifically relate to the immunophenotype or the
molecular genetics of the lesions.

4. What work-up would you recommend (include laboratory tests and diagnostic interventions)?

 In this case, we recommend a complete blood cell (CBC) count with platelet count and
differential is necessary to assess the level of blood loss in a patient with upper gastrointestinal
bleeding. Assessing calcium levels is also useful in identifying individuals with
hyperparathyroidism, but it is especially helpful in monitoring calcium in patients receiving
multiple transfusions of citrated blood. Hypercalcemia increases acid secretion.
Electrocardiography (ECG) should be considered, especially in those with underlying cardiac
disease or risk factors. Moreover, close measurement of vital signs, including continuous pulse
and blood pressure monitoring, is important and may alert clinicians to important changes in the
patient's clinical stability.
5. Define upper vs. lower GI hemorrhage and explain how this can be determined clinically. 

 Gastrointestinal bleeding can fall into two broad categories: upper and lower sources of bleeding.
The anatomic landmark that separates upper and lower bleeds is the ligament of Treitz, also
known as the suspensory ligament of the duodenum. This peritoneal structure suspends the
duodenojejunal flexure from the retroperitoneum. Bleeding that originates above the ligament of
Treitz usually presents either as hematemesis or melena whereas bleeding that originates below
most commonly presents as hematochezia. Hematemesis is the regurgitation of blood or blood
mixed with stomach contents. Melena is dark, black, and tarry feces that typically has a strong
characteristic odor caused by the digestive enzyme activity and intestinal bacteria on hemoglobin.
Hematochezia is the passing of bright red blood via the rectum.

 For the clinical manifestations of upper GI hemorrhage, you should look for evidence of chronic
liver diseases such as palmar erythema, spider angiomas, gynecomastia, jaundice, and ascites.
Pay attention to the patient’s vital signs and orthostatic vitals.

 Patients presenting with lower GI bleeds can have varying symptoms and signs. Therefore a
thorough history is necessary. Patients can present with scant bleeding to massive hemorrhage.
Abdominal examination may reveal tenderness, distension, or a mass depending on the cause.
When completing the digital rectal examination (DRE) inspect for hematochezia and anorectal
pathology, such as hemorrhoids. Studies reveal that left colonic bleeding tends to be bright red,
whereas the right colonic is usually maroon and may be accompanied with clots. However noted
in practice, bright red blood per rectum can occur in right-sided bleeds that are brisk and massive.

6. Describe the initial management of a patient with an acute GI hemorrhage, and state the indications for
fluid replacement, choice of fluids, and blood transfusion.

 Acute management of GI bleeding typically involves an assessment of the appropriate setting for
treatment followed by resuscitation and supportive therapy while investigating the underlying
cause and attempting to correct it.

 Patients with hemodynamic instability, continuous bleeding, or those with a significant risk of
morbidity/mortality should undergo monitoring in an intensive care unit to facilitate more
frequent observation of vital signs and more emergent therapeutic intervention. Most other
patients can undergo monitoring on a general medical floor. However, they would likely benefit
from continuous telemetry monitoring for earlier recognition of hemodynamic compromise.

For the treatments:

 Provide supplemental oxygen if the patient is hypoxic (typically via nasal cannula, but patients
with ongoing hematemesis or altered mental status may require intubation). Avoid non-invasive
positive pressure ventilation (NIPPV) due to the risk of aspiration with ongoing vomiting.

 IV fluid resuscitation (with normal saline or lactated Ringer solution)

For blood transfusions:

 RBC transfusion - Typically started if hemoglobin is less than 7 g/dL, including in patients with
coronary heart disease
 Platelet transfusion - started if the platelet count is less than 50,000/microL
 Prothrombin complex concentrate - Transfuse if INR is more than 2
7. What are immunohistochemistry stain for? (i.e. CD117 ; DOG1; cytokeratin; desmin).

 The diagnosis of GIST is made by immunohistochemical staining of the receptor tyrosine kinase
KIT (CD117). More than 90% of GISTs are positive for KIT expression, however some express
KIT mutation negative. Some instead harbor activating mutations in the PDGFRA gene.
Importantly, however, DOG-1 (discovered on GIST-1) and PKC-theta (protein kinase C theta) are
two immunohistochemical markers that are positive in GIST irrespective of KIT/PDGFRA
mutational status.
 Positive immunohistochemical staining for KIT (CD117) in a spindle cell type gastrointestinal
stromal tumor (GIST).

(A) Low magnification (10x) image of a section of a spindle type

GIST stained for KIT expression by immunohistochemistry. The
positive tumor cells are brown, and the surrounding tissue is
negative. Note the KIT-positive mast cells (arrows) in a lymphoid
aggregate.

(B) High magnification (20x) image shows typical membrane and

cytoplasmic KIT staining with dot-like enhanced staining of the
Golgi apparatus. The tumor vasculature does not stain for KIT.

8. How common is GIST and what is Imatinib?

 Gastrointestinal Stromal Tumor (GISTs) are rare, making

up less than 1% of all gastrointestinal tumors. Each year, approximately 4,000 to 6,000 adults in
the United States will be diagnosed with a GIST. About 60% of GISTs begin in the stomach, and
around 35% develop in the small intestine. The remaining types of GISTs usually start in the
rectum, colon, and esophagus.
 Imatinib mesylate (imatinib) is an orally administered competitive inhibitor of the tyrosine
kinases associated with the KIT protein (stem cell factor receptor), ABL protein and platelet-
derived growth factor receptors. The KIT tyrosine kinase is abnormally expressed in
gastrointestinal stromal tumour (GIST). More recently, imatinib has been approved for the
treatment of patients with advanced GIST.