Emilio Aguinaldo College

Manila
School of Medicine

Department of Pathology

Clinicopathologic Conference

Gastric Cancer with Liver Metastasis

Submitted by:
Group 6
Members:

BALDADO
CARINO
EZHILMARAN
KHAN
NASIR
PATRON
SANDOVAL
SILVERIO
TIONGSON
CHIVELA

April, 2018
 I. Clinical Abstract

This is a case of 41-year old, a Filipino from Bulan, Sorsogon, with a chief complaint
of generalized body weakness and tarry stool.

➢ History of Present Illness

- 2 months PTA:
- Patient experience abdominal pain on the epigastric area, burning in
character, 7/10 in severity, intermittent, non-radiating and not aggravated or
relieved by food intake.
- No changes in bowel movement, melena, hematochezia, vomiting or
hematuria
- No consult done. No medication taken
- 2 weeks PTA:
- There was persistence of abdominal pain, intermittent with same severity.
Associated with vomiting of coffee-ground material and passage of tarry
stools.
- No hematochezia
- No consult nor medication taken.
- Persistence of previous symptoms with generalize body weakness prompted consult
which then subsequently admitted

➢ Past Medical History

- Previous tuberculosis infection and treated for 6 months
- Other findings are unremarkable

➢ Family Medical History

- Unremarkable

➢ Personal and Social History

- Previous alcoholic beverage drinker.

➢ Review of Systems
- Positive weight loss of 50% in 2 months
- Early satiety
- Other findings unremarkable

➢ Physical Examination
- General: awake, coherent and in cardio respiratory distress
- Vital Sign: BP (90/60 mmHg), HR (86 bpm), body temperature (36.9).
Respiratory rate (21 cpm)
- HEENT: anicteric sclera, pink palpebral conjunctiva, moist lips, tongue and buccal
mucosa
- Chest / Lung: symmetrical chest expansion, no retraction, bronchovesicular breath
sounds in both upper lung files
- Heart: a dynamic precordium. normal rate, regular rhythm, point of maximal impulse
at 5th ICS LMCL, no murmur, heave or thrill
 - Abdomen: flat abdomen with normoactive bowel sounds, direct tenderness on the
epigastric area, no splenomegaly
- Extremities: grossly normal with full equal pulses

➢ Neurologic Examination
- Unremarkable

➢ Course in the Ward

Patient was admitted for 25 days.
On the 1st hospital day, there was a decreased hemoglobin level at 8.5, patient was
transfused with one unit of PRBC. Vital signs were monitored, medications were given.
Patient’s condition was stable.
On the 3rd hospital day, a bloody output was noted from NGT. Gastric lavage was
done every 6 hours until aspirate was clear. Repeat CBC showed decreased level of hemoglobin
at 5.9. Tranexamic acid 500mg TIV every 8 hours was given. Other medications continued.
Patient’s vital signs were monitored.
On the 6th hospital day, melena was noted on rectal exam. Vital signs were BP(110-
120/20-80mmHg), HR(75-83bpm), RR(20cpm) and T (36.7-37.2). Patient is in soft diet with
PNSS 1Lx80cc/hour. Advised for 5 units of PRBC transfusion. Medications: Omeprazole
40mg TIV OD, Sucralfate 1g/tab every 6 hours, Lactulose 30cc, FeSO4+Folic acid + Vitamin
B complex tablet, OD.
Subsequent Hospital Days, persistent melena with abdominal distension. Abdominal
ultrasound performed revealing ascites, beginning cirrhosis, pleural effusion, bilateral renal
parenchymal disease.

➢ Laboratory Work Ups

Table 1. Complete Blood Count

Complete Blood Count Results
Hemoglobin Decreased
Hematocrit Decreased
Platelet Decreased (2/11-2/16)
White Blood Cell Increased
Neutrophil Increased
Lymphocyte Decreased
Monocyte Normal
Eosinophil Decrease
Basophil Normal
Red Blood Cell Decrease
 RDW Increased
MCV Decreased (1/23-1/30)
MCH Decreased (1/23-1/30)
MCHC Normal

Table 2. Blood Chemistry

Clinical Results
Chemistry

BUN Increased
Crea Normal
Na Decreased
K Normal
Chloride Normal
SGPT Normal
Cl Normal
TG Normal
TC Decrease
TB Normal
DB Increased
IB Normal

Table 3. Clinical Microscopy

Test Result
 Urinalysis Physical:
Color: Yellow
Transparency: Slightly turbid

Microscopic:
Epithelial cells: Occasional
Mucus thread: Moderate
Amorphous urate: Many
WBC: 1-3/hpf
RBC: 0-2/hpf

Chemical:
Albumin: Trace
Sugar: Negative
Specific gravity: 1.010

pH: 6.0

Table 4. Radiology
Test Result
CXR PA PTB undetermined activity
Pulmonary nodule left

PFA Non-obstructive gas pattern

Whole abdomen Liver parenchymal disease superior left hepatic lobe
UTZ 3.7x3.2 with minimal ascites; Gallbladder polyps;
Normal pancreas, spleen, kidneys

Table 5. Other Work Ups

PT: 13.0 secs
Control: 10.5 secs
INR: 133
% Activity: 80.70%
APTT: 34.6 secs
Control: 25.1 secs

➢ Circumstances Surrounding the Demise:

On the 24th hospital day, patient was drowsy by arousable. Intubated and hooked on
mechanical ventilator. CVP of 8-10 cm. Several hours, vital signs suddenly drop to zero. CPR
and ambubagging was done. Epinephrine were given. Patient revived with vital signs: BP
(palpatory 60), HR(84bpm), RR (gasping with low CBG. Dopamine drip was started

On the 25th hospital day, patient is unarousable with pupils dilated at 6mm. Patient
pronounced dead.

II. Salient features

➢ History and Physical Examination

- 41-year-old, male, Filipino
- generalized body weakness
- abdominal pain epigastric area, burning in character, 7/10 severity, non-radiating, not
aggravated or relieved by food intake
- vomiting of coffee-ground material and passage of tarry stools
- previous pulmonary tuberculosis (treated for 6 months)
- previous alcoholic drinker
- positive weight loss of 50% in 2 months and early satiety
- Hypotension
- In the ward:
- melena noted on rectal exam
- abdominal distention

➢ Laboratory
- Leukocytosis
- Neutrophilia
- Lymphocytopenia
- Eosinopenia
- Decreased RBC, Hemoglobin, Hematocrit
- Increased RDW
- Decreased Platelet Ct
- Decreased MCV and MCH
- Increased BUN
- Decreased Na
- Increased Direct Bilirubin

➢ Radiology
- PTB undetermined activity
- Pulmonary nodule on left lung
- Minimal ascites
- Gallbladder Polyps
- Liver parenchymal disease superior left hepatic lobe 3.7x.3.2
- Pleural effusion
- Bilateral renal parenchymal disease
 III. Clinical events chronology

2 months prior to hospitalization

The case presentation starts with sudden onset of epigastric pain with a 7/10 scale. The
pain is non-radiating, intermittent and not relieved by food intake. The impression on this is
that an inflammatory event, defined by the pain, is localized in the epigastrium. The pain is
non-radiating, and this phenomenon suggests that the pain is not associated with neuronal
irritation involving inflammation of any organ in the epigastrium. In addition to this, the
pancreas is less likely to be involved, since its involvement would include radiation of the pain
to the back, due to its retroperitoneal location.
The pain is intermittent, meaning that its pattern can be affected by change of position
or even physical effort. The food intake was not a factor for relief or aggravation of the pain,
therefore we consider that it is less likely to be associated with abnormal gastric acid
production. There was no sign of gastrointestinal hemorrhage, and this fact reveals absence of
early gastrointestinal tract mucosal involvement.

2 weeks prior to hospitalization

All clinical profile noted 2 months PTA prevailed, without quantitative increase. This
time, the significant presentation is gastrointestinal bleeding, in the form of tarry stools and
hematemesis with coffee-ground appearance. The absence of hematochezia, rules out the
evidence of lower gastrointestinal bleeding from any pathologic condition. At this point, the
focus still remains localized at the upper gastrointestinal tract.
The bleeding is a characterization of loss of mucosal structural integrity. The nature of
the blood is darker, implying a chronic nature of the hemorrhage as well as a possible contact
with the gastric acid, which leads to oxidation of blood, and consequently transforming its
color.
Day of hospitalization
Generalized weakness now became part of the clinical profile. This is either explained
by the consequent loss of blood components, chiefly the red blood cells, chronically hence its
insidious onset. The lowered oxygen carrying capacity concomitant with chronic blood loss
without adequate physiologic compensation leads to a decrease oxygen delivery to tissue
contributing to the generalized body weakness. It is necessary to salient that the generalized
weakness only started at the day of hospitalization. (with the major etiologic factor, therefore,
being chronic blood loss, which heralded hemodynamic instability).
The patient was previously diagnosed with Primary pulmonary tuberculosis and treated
for 6 months with no additional follow up. The patient has history of alcohol consumption,
although rate of consumption was not established. These are the important data from the
history, and from it, we draw our conclusions:
On review of systems:
 Loss of more than 50% of body weight and early satiety are documented. Early satiety
may implicate inflammation of the gastric mucosa. This inflammation could either be
neoplastic or non-neoplastic. can be due to any cause of abdominal distention, delayed gastric
emptying, or cancers (most commonly gastric and pancreatic). Abdominal distention causes
stimulation of the vagus nerves which causes satiety and meal termination. The weight loss of
about 50% in two months is accelerated and the implication of malignancy is to be considered.
Another possible explanation of this, is the fact that the patient could not eat properly, hence
the weight loss.
On physical examination, the only abnormal vital sign was the blood pressure
(90/60mmHg). This concedes with the chronic blood loss through the G.I. With the low
diastolic pressure, implies low. The temperature is within normal range, no consideration of
systemic inflammatory event is taken.
Cardio-respiratory distress is also noted. This feature represents hemodynamic
instability, whose etiology is either characteristic of pulmonary disease, or a decrease in the
blood pressure, leading to pulmonary parenchyma hypoperfusion and impaired gas exchange,
causing metabolic acidosis and hyperventilation

IV. APPROACH TO DIAGNOSIS

In accordance with the symptoms listed, we as a team of clinical pathology students, will direct
our focus on the liver parenchyma, hepatobiliary tree and upper gastrointestinal tract

➢ Upper GIT

All clinical presentations seen in the case as very well consistent with chronic upper
gastrointestinal inflammatory processes, from non-neoplastic to neoplastic. Other probable
diagnosis in consideration is gastrointestinal TB.
The symptom of epigastric pain presented in the 2 months prior to admission is
consistent with upper GI involvement. This assumption comes with the fact that the patient has
pulmonary tuberculosis, and the epigastric pain may as well be a representation of a metastatic
phenomenon of the TB from the lungs, either via hematogenous spread or lymphatic spread.
Only CT scan and ultrasound will confirm our presumption. The upper GI involvement that we
refer to, if it presents with mucosa inflammation, may explain the bleeding that manifests as
melena or hematemesis, and again, the employment of endoscopic studies will confirm our
presumption.
For non-neoplastic, we considered metastatic tuberculosis, though primary
gastrointestinal tuberculosis is another acceptable differential for us as, since this is very well
consistent with the past illness of Pulmonary TB. No other non-neoplastic chronic differential
was found to be consistent with the case.
For neoplastic, we considered any gastrointestinal malignancy, we cannot specify
which, since the pathophysiologic description of either advanced localized or metastatic is that
of localized GI pain, and bleeding for most scenarios. And only endoscopy and histopathologic
studies will define what type of malignancy is in question. The involvement of the left lobe of
the liver, may have been associated with a transmural advance of the malignancy (most
possibly gastric cancer) into the liver parenchyma.
 A possible secondary (metastatic) malignancy can also be considered. A metastatic
spread from anywhere near the viscera or even distant places may have occurred, and for that,
further diagnostic evaluation is to be done. In this same presumption, we considered the
possibility of a hepatocellular carcinoma involving the left lobe of the liver and spreading
directly to any gastrointestinal structure near the left side of the liver, and transmural invasion
of the structure in question and causing localized GI chronic inflammation and bleeding. To
confirm our clinical diagnosis, a CT scan and MRI studies will be needed.

➢ LIVER

The left hepatic lobe was found to be smaller than normal, this may indicate a chronic
inflammatory process that resulted in loss of normal parenchyma, and fibrosis (cirrhosis). The
inflammatory process may have had an underlying neoplastic or non-neoplastic disease.
For non-neoplastic, we considered metastatic tuberculosis to be the most consistent
cause for this case. The tuberculous complex from the lungs may have metastasized via
hematogenous or lymphatic spread from the lungs. Considering the location of the lesion
(localized), we consider rupture of a para-aortic tuberculous lymph node, invasion of the liver
capsule and consequent parenchymal infiltration of the superior left lobe of the liver. This may
be theoretically validated, in the fact that the liver is only partially involved, hence the near
normal liver function tests at the time of admission. The assumption may also explain the
epigastric pain, though it does not explain the upper GIT symptoms at first glimpse. The upper
GIT involvement, however, may be explained by the transmural invasion of the GI structures
surrounded by the same ruptured tuberculous lymph nodes, leading to chronic inflammation
and mucosal bleeding.
Alcoholic liver disease, is also brought into consideration for the fact that it is listed in
the patient’s history, that he was an alcoholic beverage drinker. The cirrhotic effect of alcohol
is well documented. The history is not specific on the patient's rate of alcohol consumption,
and the diagnostic test ordered only indicated minimal cirrhosis of the liver parenchyma.
Another important fact is that the data in the case only stated beginning of cirrhosis, without
further details on the degree of hepatic involvement. Hence, further diagnostic tests are to be
obtained in order to qualify cirrhosis secondary to chronic alcohol consumption. The liver
function tests are near normal, and this, theoretically, implies that the cirrhotic process is not
diffuse, rather localized. Yet, if the cirrhotic process proved to be diffuse, the finding would
explain the presence of gastrointestinal involvement (bleeding, chiefly) primarily stemming
from portal hypertension with underlying periportal hepatic fibrosis. The same finding would
also explain the Obstructive Jaundice caused by extrahepatic and/or intrahepatic bile duct
stenosis through ductal fibrosis.
For neoplastic, hepatocellular carcinoma came into light. The disease process depicted
by imaging studies for the case, as mentioned above, is a size decrease of the superior left lobe,
theoretically from cirrhosis. In this view, the underlying chronic inflammatory process is
elicited by the malignant proliferation of hepatocytes. It is well known that hepatocellular
carcinoma has its histologic variants, which can only be well characterized in histopathologic
studies. In this light, we assume that the neoplastic behavior is highly variable.
Notwithstanding, the presence of epigastric pain, may, therefore have its origin from the
neoplastic inflammation. The gastrointestinal involvement is explained either by the cirrhotic
effect on the portal vascular integrity, leading to gastrointestinal submucosal venous
congestion, and consequent bleeding, or, very unlikely, the direct spread of the hepatocellular
carcinoma into the adjacent gastrointestinal structure (transmurally) with mucosal extension
and consequent bleeding. The extra and/or intrahepatic biliary involvement, manifested with
the elevated ALP and direct bilirubin, stems from the inflammatory as well as cirrhotic on the
intrahepatic bile ducts

➢ INTRA AND/OR EXTRAHEPATIC BILIARY TREE

We considered the isolated involvement of the intra and/or extrahepatic bile ducts, in
the light of the facts that direct bilirubin is elevated as compared to indirect bilirubin, as well
as ALP is elevated, giving us the idea that the underlying cause may be inflammatory in nature,
as well as obstructive. Thus, non-neoplastic and neoplastic pathologic conditions come into
light.
For non-neoplastic, giving the case presentation, we make the diagnostic inclusion of
tuberculous choledocholangitis of metastatic nature, giving the history of primary pulmonary
tuberculosis. The inflammatory process elicits pain, thus explaining the epigastric pain
observed in the case. Chronic inflammation leads to stenosis of the bile ducts and cholestasis,
hence the elevated direct bilirubin and tea colored urine.
For Neoplastic conditions, we include any form of bile duct as well as gallbladder
neoplasia either primary (benign or malignant) or secondary, which can either be metastatic or
externally compressive. Neoplastic malignant nature is of most consideration, because of the
pain, most probably elicited by the chronic inflammation. Bile duct obstruction can be caused
by tumor growth into the lumen or by chronic inflammation resulting into ductal fibrosis and
stenosis. The result is the same as that of cholestasis, elevation of direct bilirubin as well as tea
colored urine, as noted in the case. A question may arise on how the upper gastrointestinal
symptoms of chronic bleeding came into existence.

V. DIFFERENGTIAL DIAGNOSIS

Having given our diagnostic work up, we made our differential diagnosis as the following:
1. Hepatocellular Carcinoma

2. Metastatic Abdominal Tuberculosis, with renal, gastric and Hepatobiliary involvement

3. Alcoholic Liver Disease

4. Chronic Pancreatitis

5. Gastric Cancer

RATIONALE:
 ➢ Hepatocellular Carcinoma

Rule In Rule out

Risk Factors: Chronic alcohol intake, Anti- Risk Factors: Hepatitis B or C infection
TB drugs (hepatotoxic), possible (strongest association with HCC)
schistosomiasis infection (Sorsogon)
Symptoms: Epigastric pain, generalized
body weakness
Signs: Cachexia (early satiety and weight Signs: Absent splenomegaly
loss of 50% in 2 months, gastrointestinal
bleeding evidenced by melena and
hematemesis, ascites, beginning cirrhosis,
direct tenderness on epigastric region,
pleural eff usion
Diagnostics: no mass seen on
ultrasonography, (<2cm may not be seen on
UTZ or may manifest cirrhosis) normal
SGPT

In a study done by the department of internal medicine of the UP-PGH, the clinical
profile of hepatocellular carcinoma is that they occur more commonly in males (M:F 4:1), in
the age range of 29-86 (a mean age of 54), and that most of the patients complain is abdominal
pain. The patient was said to be an alcoholic drinker which could contribute to an increased
risk of developing hepatocellular carcinoma because of its effects on the liver, primarily
cirrhosis. There was also mention of the patient undergoing TB treatment and the anti-TB drugs
are known to be hepatotoxic.

Exposure to the risk factors mentioned above, can lead to chronic inflammation.
Inflammation may stimulate the visceral/peritoneal nerves causing pain. Epigastric pain is the
most common presentation seen in patients with hepatocellular carcinoma.

Erythropoietin is a glycoprotein that promotes the proliferation and differentiation of

erythrocyte precursors. The major site of EPO synthesis is in the kidney, while extrarenal
production is in the liver. Hepatocellular carcinoma causes liver dysfunction which in turn
causes a decrease in the synthesis of EPO, thereby affecting erythrocyte synthesis causing the
patients anemia. Anemia leads to a decrease delivery of oxygen to the tissues leading to the
patients fatigue/weakness. Fibrosis of the liver, and mass effect of the tumor can block the
portal circulation, this causes portal hypertension and increases intravascular pressure
contributing to fluid shifting and ascites. The portal hypertension and a decrease in oncotic
pressure can cause hydrothorax/pleural effusion. If the portal circulation is blocked, blood back
flows from the liver to the esophageal and gastric vessels which could lead to
gastric/esophageal varices, and eventually rupture which would explain the hematemesis and
melena of the patient. Anorexia, early satiety, and unintended weight loss of 10% in 6-
12months is suggestive of cachexia. Cachexia is considered a danger/warning sign in of any
malignancy and often denotes advanced stage of the disease.
RULE OUT

Risk Factors:
• Hepatitis B or Hepatitis C infection are the most common risk factors that have a strong
association with the development of HCC. There was no mention or laboratory to confirm
hepatitis infection.
• Alpha-1-antitrypsin deficiency and aflatoxin intake/use also have significant risk in
developing the disease which is absent in our patient.

Signs:
• Splenomegaly usually develops in the course of HCC.
• Jaundice is also absent which may be a sign of metastasis to the biliary tree

Diagnostics
• No mass seen on the whole abdominal ultrasound. A mass is usually seen in an abdominal
ultrasound but some might not be seen especially those less than 1cm or those who have a
diffuse-type HCC.
• The patient has normal SGPT (ALT) serum level. ALT is usually present in the heart and
in the liver. It becomes elevated when it is released into the blood as a result of damage. In
our case since we are considering HCC, there should be an elevated ALT serum level.

➢ Metastatic(Disseminated) Abdominal Tuberculosis

Rule In Rule Out

Ascites (-) Fever (low grade)
Anemia (-) Obstruction
Neutrophilia (-) Night sweats
Weight loss (-) increased ESR - no result
Loss of satiety (-) hematochezia
Abdominal pain
Leukocytosis - Neutrophilic (Occasional)

Abdominal (Gastrointestinal TB) tuberculosis is usually uncommon and having small

percentage for extrapulmonary cases. Most commonly abdominal TB are found in the terminal
ileum and the cecum. Pathogenic mechanisms to the cause of the disease was due to:

• Oral intake of infected sputum which had caused direct seeding

• Hematogenous spread
• Lymphatic spread

Predominantly this disease is found on young adults. Clinical presentation of the

disease are weight loss, malaise and anorexia which are found on the patient. Other symptoms
not pertinent on the case were fever (low grade), chronic cough and night sweats. Symptoms
specified were found to be due to cytokines released by activated macrophages and not by the
organism indicated. Other symptoms presented that are indicative of abdominal TB were
abdominal pain and ascites which may possibly signify tuberculous peritonitis. Weight loss in
the case is also a finding of a TB infection. Obstruction is also one of the common findings but
is not observed in our patient.

Hematologic findings which can correlate with the case would be presence of anemia
which is usually mild. Presence of Leukocytosis with neutrophilia found in our case can be
correlated to the Abdominal TB which is occasionally found as compared to the usual
lymphocytic type of Leukocytosis.

➢ Alcohol induced hepatitis

Rule in Rule out

Previous Alcoholic Drinker (-) Jaundice

Abdominal Pain (-) Fever

Malnutrition (Weight loss) (-) Tachycardia

GI Hemorrhage (Hematemesis and Melena) Tender Enlarged Liver

Hyperbilirubinemia Edema

Splenomegaly

Thrombocytopenia

According to Basra et al, alcohol induced hepatitis are seen in patients with alcohol
consumption history of over 80g of ethanol for over 5 years. However, the duration of drinking
before the onset of liver disease varies from 3months to 36 years as well as abstinence of more
than 3 months is unlikely to be associated with diagnosis of AH.
Specific signs and symptoms that can be seen in AH are Clinical jaundice (40-60% of
cases), hyperbilirubinemia which is considered a cardinal feature of the disease. Others also
report right upper quadrant pain, fever, tachycardia and tender enlarged liver. Other nonspecific
signs and symptoms such as nausea, vomiting, malaise and anorexia may also be related to
AH.

In severe cases, patients may present with hepatic encephalopathy, renal failure or
hepatorenal syndrome, ascites due to portal hypertension and bleeding tendencies due to
coagulopathy and thrombocytopenia. Malnutrition is also seen in 90% of patients with AH but
it can be due to Kwashiorkor or Marasmus.
 ➢ CHRONIC PANCREATITIS

Rule In Rule out

(+) weight loss of 50% in 2 months fatty stool

abdominal pain patient is not a smoker

Vomiting Hypercalcemia

alcoholic beverage drinker Diarrhea

tenderness on the epigastric area Diabetes mellitus

Chronic inflammatory disease of the pancreas characterized by irreversible

morphological change and typically causing pain and/or permanent loss of function. Chronic
pancreatitis is beset by destruction of healthy pancreatic tissue and the development of fibrous
scar tissue. Gradual loss of exocrine and endocrine function ensues with clinical manifestations
such as steatorrhea, abdominal pain, and diabetes.
The presenting symptom of most patients with chronic pancreatitis is abdominal pain,
usually epigastric, dull and constant in nature. It is almost always localized in the upper half of
the abdomen, from which it can radiate directly through to the back, or laterally around to the
left or right flank. Initially the duration of pain is quite variable, ranging from several hours to
several days, but as the disease progresses the attacks become more frequent and pain-free
intervals shrink and vanish. Chronic pancreatitis can be entirely silent, and in presentation
patients may present with the sequelae of exocrine or endocrine insufficiency: steatorrhea,
weight loss and diabetes. Less common initial presentations include biliary obstruction with
recurrent episodes of mild jaundice, cholangitis, or vague attacks of indigestion.

Ø Diagnostic impression: Gastric cancer with hepatic metastasis

Pathophysiology and Literature review for Gastric cancer.
The following review, explains clinical events in a case of Upper GI cancer, which are similar
to the given case.

➢ GASTROINTESTINAL SYMPTOMS

According to Malfertheiner et al., weight loss, dysphagia, signs and symptoms of upper
gastro-intestinal bleeding, anemia and persisting vomiting were the alarm symptoms that are
more frequently associated with upper gastro-intestinal malignancies. And immediate
endoscopy was recommended by most of the guidelines for all the patients presented with these
symptoms.3

➢ ANEMIA
Birgegard et al. stated that the result of complex interactions between tumor cells and
the immune system is cancer-related anemia. A shortened survival of red blood cells,
suppression of erythroid progenitor, impaired iron utilization and inadequate erythropoietin
production were the result of over expression of certain inflammatory cytokines.4

➢ EARLY SATIETY AND WEIGHT LOSS

Based on the journal of Livstone et al., if the cancer obstructs the pyloric region or if
the stomach becomes non-distensible secondary to lienitis plastic, early satiety may occur.5

➢ COFFEE GROUND EMESIS AND MELENA

Ansari et al stated that because of upper GI bleeding that has slowed or stopped and the
gastric acid converted the red hemoglobin to brown hematin will coffee ground emesis will
occur.6

McMorran et al defined melena in their website as a bleeding in the early

gastrointestinal system proximal to the splenic flexure of the colon such as esophagus, stomach
and duodenum. They also stated that melena occurs if there is loss of more than 60 ml of blood
in the upper gastrointestinal tract.

➢ ASCITES
Based on the journal of Saif et al, ascites is related to portal hypertension which is
usually related to liver cirrhosis. The major pathophysiologic mechanism in the formation of
ascites is the lymphatic obstruction, but there are evidences that suggest immunomodulators,
vascular permeability factors and metalloproteinase contribute significantly to the process.
Peripheral arterial vasodilation leading to underfilling of circulatory volume is the most
acceptable theory for the ascites formation. 8

➢ Pathogenesis of Pleural Effusion

 According to Fukanoshi et al, breast, GI and lung cancers are the common causes of
pulmonary lymphangitis carcinomatosis. Though little is known about the disease in relation
to advanced GI cancer.9
Though in some studies, it is believed that it develops from loss of adhesion and
dislodgement of tumor cells from the site, adherence and penetration of the blood vessel wall,
migration to the pleura, production of growth factors and blocking of lymphatic tracts.
Sun et al, stated that in immunocompetent mouse models of tumor induced MPE,
revealed another pathway for MPE formation. The vicious interactions between tumor cells
and host vascular and immune systems contribute to MPE development. The pleural levels of
vasoactive mediators, including vascular endothelial growth factor, tumor necrosis factor,
chemokine ligand 2, osteopontin and possible protective molecules (e.g., endostatin) dictate
the occurrence of vasoactive events and, ultimately, the MPE development. Also, it has been
shown previously that myeloid cells such as macrophages, neutrophils, and eosinophils can
induce MPE pathophysiology.

➢ Neutrophilia

According to Fu et al, an increase in neutrophils were seen in gastric cancer tissues

and also, they were found in gastric metaplasia tissues compared to normal gastric tissues.
An increase in neutrophils in gastric cancer is related to an increase of chemoattractant
IL-8. In gastric CA, higher numbers of neutrophils were seen in patients regardless of their age,
tumor stage, depth and invasion, and metastasis and cancer type. Which concludes that an
increase in neutrophils is associated with downregulating of E-cadherin, cell proliferation and
gastric carcinogenesis.

➢ Increased BUN and Direct Bilirubin

BUN and creatinine may be measured to check kidney function. Increase in both
parameters are indicative of metastasis of CA to the ureters or kidneys.

The Canadian Cancer Society states that lactate acid dehydrogenase, ALK,
transaminase and Bili can be measured to check liver function. An increase in these parameters
would also indicate metastasis to the liver.
Tomizawa et al suggest that BUN also represents products of protein metabolism via
ammonia. When GI bleeding happens, blood is digested to protein and the protein is then
transported to the liver via the portal vein and metabolized into BUN. Higher BUN values
mean increased digestion of blood.

➢ Decreased Sodium and Potassium.

According to Shirali, A.C., hyponatremia can be seen in 14% of hospitalized patients

based on a observational cohort study. Though it can be caused by other etiologies, SIADH is
the most common etiology observed among patients which can be attributed to cancer.
Primarily because CA patients have a nonvolume and nonosmotic stimuli for antidiuretic
hormone release, which presents as nausea/vomiting, pain or medicine related such as intake
of cyclophosphamide.
 Shirali also stated that hypokalemia is the second most common electrolyte disorder
found in patients with cancer.
Though according to Bowman, B.T., hypokalemia is multifactorial and cancer patients
with this condition are often caused by malnutrition, transcellular potassium shifts and GI and
Renal losses. Though their mechanisms can be different in cancer. GI losses can be a source of
potassium lost and often caused by diarrhea, constipation and GI tumors with a mechanism of
action in the intestinal and colonic BK potassium channel regulation.

➢ Bilateral Renal and Parenchymal Disease.

Choyke et al states that bilateral renal metastases occur most commonly in the late
stages of malignancy. It is usually asymptomatic and hematuria or microhematuria are seen in
only 12-13% of patients. Lung cancer is the most common malignancy to have kidney
metastases, followed by breast cancer, gastric cancer and melanoma. However almost any late
stages can metastasize to the kidney.

➢ Increased Direct Bilirubin

According to Quidde et al an increase in direct bilirubin is caused by the anatomical

location and venous drainage of the liver, which is the predominant organ for metastatic
manifestations arising from the GI Tract. An impaired liver function and liver failure is
commonly see in GI cancer patient. An increase in

VII. CONCEPT MAP

 VIII. CLINICAL EVENTS

✓ The chronic gastrointestinal bleeding causes a significant decrease in the blood volume.

✓ A possible metastasis to the liver lead to the inflammation of the affected hepatic
parenchyma and development of ascites.

✓ Cirrhosis is a major complication of the chronic malignant inflammatory process.

✓ Ascites resulted in a significant decrease of the plasma volume with consequent

hypovolemia.

✓ Back flow of blood into the gastrointestinal circulation led gastrointestinal vascular disease.
Gastrointestinal mucosal varices developed and ruptured, causing hemorrhage. This
explains the source of the bleeding manifested as melena/hematemesis, and the resulting
anemia.

✓ Hepatic hypoperfusion lead to hepatic dysfunction which decreased the protein synthesis
rate comprising of low erythropoietin (causing anemia) low thrombopoietin (causing
thrombocytopenia) low albumin (causing edema) and low lipoprotein (causing
hypocholesterolemia).

✓ Renal hypoperfusion lead to Acute Kidney Injury, manifested as decreased renal clearance
of nitrogenous wastes, increase in BUN, and ultimately uremia.

✓ Pulmonary hypoperfusion, manifested as low oxygen concentration and respiratory distress

due to pulmonary edema. And later in the course, respiratory depression set in.

✓ The intestines are also involved by hypoperfusion, which results in necrotizing

enterocolitis. The intestinal pathogenic bacteria proliferate and eventually invade the
vascular system and cause bacteremia and sepsis (SIRS like syndrome), reflected by
elevated neutrophil count.

✓ From day 9 to day 12 Disseminated Intravascular coagulation was characteristic and was
defined progressive severe decrease in the platelet count and, although not recorded in the
lab results, abnormal PT and APTT which reflect consumptive coagulopathy.

✓ The hypoperfusion involves the heart, causing myocardial infarction and heart failure

✓ Accumulation of metabolites in the brain causes an increase in the glutamate activity. This
causes neurotoxicity and liquefactive necrosis, cerebral edema and an increase in the
intracranial pressure, altered sensorium and ultimately coma.

✓ Multiple organ failure from hypovolemic shock resulted in the demise of the patient.

1- Underlying disease: Gastric Cancer with liver metastasis

 2- Antecedent cause of death: Hypovolemic chock

3- Immediate cause of death: Multiple organ failure

IX. Final Impression:

Multiple organ failure secondary to hypovolemia, precipitated by ascites due to liver

metastasis of gastric cancer
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