Download - Annals of Gastroenterology

Oncological emergencies associated with
gastrointestinal tumors.
Klaas Prenen, Hans Prenen*
Comments to the reviewers
We would like to thank the reviewers for their constructive comments. Here you can find point by
point the changes that have been incorporated in the manuscript according to the questions of the
reviewer. Changes in the manuscript have been highlighted in yellow.
*Corresponding author:
Hans Prenen, MD PhD
University Hospitals Leuven
Department of Gastroenterology
Digestive Oncology Unit
Herestraat 49
B3000 Leuven, Belgium
Phone: +32 16 34 42 18
Fax: +32 16 34 44 19
Email: [email protected]
REVIEWER 1
1) The authors emphasize at the main body of the paper that some emergencies, for example
superior vena cava syndrome or brain metastases, are associated more common with other types
of cancer rather than gastrointestinal tumors. The authors choose to describe these emergencies
considering a rising incidence of them because of the longer survival of patients with
gastrointestinal tumors. Their assumption is acceptable and justified. This takes me to a point
that it would be more preferable at the end of the introduction and in the conclusions to clarify
that as they can mislead the reader that the describing emergencies can be only associated with
gastrointestinal tumors or presenting commonly with gastrointestinal tumors.
Reply: We thank the reviewer for this constructive comment. We added the following sentence in
the introduction : “While some emergencies such as hematological emergencies, bleeding and
intestinal obstruction are more common in GI oncology, we decided to describe as well the less
frequent emergencies associated with GI tumors, as their incidence is rising due to the longer
survival of cancer patients.
Furthermore we added this sentence to the conclusion section: “Some emergencies occur more
frequently in patients with GI tumors such as bleeding and intestinal obstruction, while others are
less frequent, but nevertheless important to recognize.”
2) I was wondering if the authors would consider the possibility to discuss the subject of disseminated
intravascular coagulation, a life-threatening situation, which can complicate a large number of
patients with solid tumors including patients with pancreating cancer
Reply: We added the following chapter on disseminated intravascular coagulation (DIC) in the
section of hematological emergencies:
Disseminated intravascular coagulation (DIC)
Disseminated intravascular coagulation (DIC) is a potential life threatening condition,
characterized by an abnormal activation of coagulation and fibrinolysis leading to
thrombosis and hemorrhage simultaneously [13]. It occurs in a variety of diseases,
including cancer [14]. About 10 to 15 % of metastatic cancer patients have some evidence
of DIC. It is mostly associated with acute leukemia, but can also occur in mucinous tumors
such as pancreatic and gastric cancer [15]. Some patients have only a mild clinical course
with consumption of coagulation factors while others present with life-threatening
bleeding. Treatment consists of treating the underlying cause in combination with
supportive measures such as hemodynamic support, hydration and transfusion.
3) To the same pattern I would like to propose to authors to include pulmonary thromboembolism
common emergency in patients with cancer because of their hypercoagulable state, local tumor
effect or treatment side effects which can present with malignant tumors often with colon cancer.
Reply: We added the following section on pulmonary thromboembolism:
Pulmonary thromboembolism
Patients with cancer are in a hypercoagulable state and thus more likely to develop venous
thromboembolisms [34]. The risk is further increased by the administration of chemotherapy.
Thrombotic events are even the second leading cause of death in cancer patients. The risk of
thrombosis varies by cancer type and is especially high in pancreatic, gastro-esophageal, brain and
lung cancer [35]. Acute pulmonary thromboembolism (PTE) is very common in cancer patients,
with a highly variable clinical presentation from no symptoms to shock or sudden death. The most
common presenting symptom is dyspnea at rest. Treatment should focus on stabilizing the patient
and start of anticoagulation, as untreated PTE is associated with a mortality of around 30 percent.
The benefit of anticoagulation should always be weighed against the risks such as in patients with
bleeding or with limited life expectancy. Low molecular weight heparines are the treatment of
choice in cancer patients, especially when treated with chemotherapy. Newer oral anticoagulants
have not been studied in cancer patients. When anticoagulation is contra-indicated such as in cases
of bleeding or low platelets, the placement of a vena cava filter may be considered.
4) At the section of gastrointestinal bleeding if there is the possibility to supplement it with the case
of abdominal bleeding as a result for example of rupture of hepatocellular carcinoma.
Reply: As suggested by the reviewer we added the following sentence to the section of
gastrointestinal bleeding: “In patients with a hepatocellular carcinoma, spontaneous rupture can
occur resulting in hemoperitoneum and hemorrhagic shock. Predisposing factors are subcapsular
location, large size of the tumor, portal hypertension and tumor necrosis [23].”
REVIEWER 2
1) Citations are needed at the following parts of the text:
a. Page 3, line 6, after “asymptomatic disease”
b. Page 3, line 7, after “polyps”
c. Page 3, line 10, after “stage”
d. Page 4, line 7, after “microliters”
e. Page 4, line 11, after “complications”
f. Page 6, line 22, after “dysfunction”
g. Page 8, line 12, after “treatment”
Reply: We added the citations as requested by reviewer 2
2) The phrase starting with “However…” in page 6, line 5 and ending in line 8 needs rephrasing to
become clearer.
Reply: We changed the sentence to: “However, because of the increased overall survival of colon
cancer patients due to the recent advances in the treatment of systemic disease and because of
the poor delivery of chemotherapeutic drugs across the blood brain barrier, chances to develop
SCC secondary to vertebral metastases are likely to raise”
3) In Page 7, line 1, the phrase “in a metastases” is not grammatically right (“a” should be
removed).
Reply: We deleted “a”
4) In page 9, line 20, commas should be added after “Often” and “however”.
Reply: Commas have been added