Difference between revisions of "Intestinal Adenocarcinoma"

Revision as of 10:57, 19 August 2009

Intestinal tumours are uncommon accounting for less than 10% of all tumours in dogs and cats and 22% of gastrointestinal tumours in dogs and 35% in cats. It has been reported that the jejunum, ileum and caecum are the most frequent sites affected in the dog. Intestinal tumours in dogs and cats are usually malignant, Adenocarcinoma/carcinoma being the most common malignant tumour in dogs and accounts for 17% of intestinal tumours in cats.

Signalment

Dogs:
- Mean age: 6-9 years
- Minor male predisposition
- Large breeds may predominate particularly collies and German Sheperds and Boxers

Cats:
- Mean age: 10-12 years
- There are conflicting reports of whether there is a minor male predisposition
- Siamese may have a breed predisposition

Description

No organism or chemical agent has been identified that will induce spontaneous intestinal adenocarcinoma.
The gross appearance of colorectal adenocarcinomas vary from pedunculated, particularly in the distal rectum, cobblestone, in particularly the middle rectum, or annular, also usually in the middle recutum, and may also have associations with tumour behaviour and prognosis.
In cats, adenocarcinomas have been reported to have been found in the ileum and ileocaecal region. Another study reports the jejunum to be the most common site.
Metastasis occurs via lymphatic and vascular routes. For small intestinal adenocarcinomas the most frequent sites of metastasis are the mesenteric lymph nodes. Other sites include the liver, kidneys, peritoneal cavity, omentum and lungs. Metastatic spread is commonly encountered at time of diagnosis.
Large intestinal adenocarcinomas often metastasise to the deep inguinal lymph nodes. The liver is less frequently affected. These tumours also undergo aggressive local growth and local recurrence after resection frequently occurs.

Diagnosis

Clinical Signs

Usually chronic and often dependent on the site of the tumour within the gastrointestinal tract and include:

For more proximal lesions:
- vomiting
For lesions within the small intestine:
- Weight loss
For tumours in the more distal tract:
- Tenesmus
- Hematochezia
- Faeces may be altered in shape with constricting lesions
Other signs reported include:
- Anorexia
- Diarrhoea
- Signs associated with acute intestinal obstruction (usually when the tumour has grown in an annular form), perforation and peritonitis

Associated paraneoplastic abnormalities include:

Neutrophilic leukocytosis
Monocytosis
Eosinophilia
Cutaneous disease
Hyperviscosity syndromes

Physical Examination

An abdominal mass may be palpable
A rectal and potentially a lower colonic mass may also be palpable digitally via rectal examination
Cats may also be dehydrated

Haematology and Biochemistry

Abnormalities observed include:

Anaemia
Leukocytosis
Left shift
Monocytosis
Hypoproteinemia
Raised hepatic enzymes
High cholesterol
Raised BUN - may be due to concurrent renal insufficiency, dehydration or absorption following intestinal bleeding
Electrolyte abnormalities - due to intestinal obstruction

Abdominal Radiography

An abdominal mass may be visible with plain radiography
Alternatively evidence of obstruction may be observed
Poor serosal detail may be apparent
Contrast radiography can be useful for localising masses, revealing obstructions and filling defects and for intestinal areas more difficult to visualise via ultrasonography due to the accumulation of air.

Thoracic Radiography

This is highly advised though presentation with pulmonary metastasis is infrequent.

Abdominal Ultrasonography

Is more sensitive than radiography in localising a mass and can assess involvement of surrounding structures. In addition, guided needle aspiration or biopsy may be taken at this time. Findings may include the following:

Intestinal wall thickening with loss of wall layering - dogs with loss of layering are over 50 times more likely to have neoplastic disease rather than enteritis
In cats, adenocarcinomas have been described as being of mixed echogenicity and are often asymmetric
In dogs, adenocarcinomas have been described as being usually hypoechoic and most dogs had reduced gut motility

Endoscopy and Laparoscopy

Allow visualisation of the lesion. In addition, biopsies may be taken at this time. Open proctoscopes are more useful than fibreoptic scopes for colorectal lesions as direct visualisation of the mass is possible and deeper biopsies can be obtained. Nevertheless, often only small superficial samples can be obtained on biopsying the gut thus there can be significant variation in the interepretation of the findings.

Exploratory Laparotomy

Definitive diagnosis requires an excisional biopsy. All abdominal tissues should be assessed and full thickness biopsies taken. Resection of the mass and intestinal anastomosis may be performed at this time.

Treatment

Surgery

Surgical excision is advised as primary treatment for intestinal adenocarcinoma. Extraserosal invasion or adhesions may cause difficulties and care must be taken to ensure there is no iatrogenic damage to the biliary and pancreatic ducts for duodenal lesions. In the small intestine, wide local resection (4-8cm margins) can usually be achieved via enterectomy and anastomosis. Stapling and suturing by hand have been shown to be equally efficient for this procedure. If appropriate regional lymph nodes should also be removed. Large margins may be more difficult to achieve for colorectal lesions due to access issues. Perioperative complications include peritonitis and sepsis.

Adjuvant Chemotherapy

Doxirubicin has been shown to significantly improve survival times for cats with colonic adenocarcinoma with median survival times of 56 and 280 days for those not receving and those receiving chemotherapy respectively. No other evidence exists to confirm the benefits of adjuvant chemotherapy in dogs or cats. Piroxicam, a non-steroidal anti-inflammatory drug may have beneficial effects for rectal malignancy.

Radiotherapy

Rarely reported due to concerns of intolerance of surrounding tissues leading to for example perforations and adhesions, in addition it cannot be relied upon that the same target will be irradiated each day due to intestinal mobility. There has been a report of single high-dose iradiation being used for anorectal adenocarcinomas which had been surgically exposed and no long-term side effects were observed.

Prognosis

If no metastasis has occurred long term survival may be achieved following wide excision of a well differentiated small intestinal tumour. The rate of metastasis of adenocarcinoma to the local lymph nodes for both dogs and cats is approximately 50%. Without surgical intervention the mean survival of dogs with small intestinal adenocarcinoma is 12 days and reports varying from 114 days to 7-10 months with surgical treatment. Intensity of treatment is prognostic for colorectal tumours with palliative care carrying a poorer prognosis than local excision. In one study males with small intestinal adenocarcinoma had a significantly better prognosis than females with the same disease though the sample size was small. Local excision of colorectal adenocarcinoma has a median survival time of 22 months while the use of stool softeners alone has a median survival time of 15 months.

There is significant perioperative risk associated with cats with small intestine adenocarcinoma with a high mortality rate within the first two weeks following surgery. However, after these two weeks long term control may be achieved. For cats with large intestinal adenocarcinoma survival time after surgery alone has been reported as approximately 4.5 months.

References

Liptak J. M, Withrow S.J, (2007), Cancer of the Gastrointestinal Tract, in Withrow and MacEwen's Small Animal Clinical Oncology, fourth edition, Eds Withrow S.J, Vail D.M, Missouri, Saunders Elsevier, pp 491-501
White, R. A. S, (2003), Tumours of the intestines, in BSAVA Manual of Canine and Feline Oncology, second edition, Eds Dobson J. M, Lascelles B. D. X, Gloucester, British Small Animal Veterinary Association, pp 229-233

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-{{OpenPagesTop}}
+{{Unfinished}}
-==Introduction==
+Intestinal tumours are uncommon accounting for less than 10% of all tumours in dogs and cats and 22% of gastrointestinal tumours in dogs and 35% in cats. It has been reported that the jejunum, ileum and caecum are the most frequent sites affected in the dog. Intestinal tumours in dogs and cats are usually malignant, [[Intestine Proliferative - Pathology #Adenocarcinoma|Adenocarcinoma]]/carcinoma being the most common malignant tumour in dogs and accounts for 17% of intestinal tumours in cats.
-Intestinal adenocarcinomas are a reasonably common malignant neoplasm of dogs and cats arising from the epithelial lining of the gastrointesinal tract. As yet, no causative organism or chemical agent has been identified for intestinal adenocarcinomas, but experiments have suggested that nitrosamines may have a role. Intestinal adenocarcinomas can be nodular or annular in appearance. By the time of diagnosis, they have often metastasised via the lymphatic and vascular routes, most commonly to the mesenteric lymph nodes. Other sites of metastasis include the liver, kidneys, peritoneal cavity, omentum and lungs. Intestinal adenocarcinomas display aggressive local growth and invasion, and tumours frequently recur after resection.
 ==Signalment==
+* Dogs:
+** Mean age: 6-9 years
+** Minor male predisposition
+** Large breeds may predominate particularly collies and German Sheperds and Boxers
-Dogs are more commonly afflicted with intestinal adenocarcinoma than cats. Intestinal adenocarcinomas have been seen in animals between the ages of 3 and 13 years, but most cases are seen in middle aged to older animals. The mean age of occurrence is 6 to 9 years in the dog, and 10 to 12 years in the cat. There appears to be a predisposition in males, and this is more pronounced in dogs than in cats. There are no breed predispositions.
+* Cats:
+** Mean age: 10-12 years
+** There are conflicting reports of whether there is a minor male predisposition
+** Siamese may have a breed predisposition
-==Diagnosis==
-===Clinical Signs===
-Dogs and cats present with a history of gastrointestinal signs. Tumours of the small intestine are associated with [[vomiting]], weight loss, melaena, flatulence and borborygmus, and large intestinal adenocarcinoma can cause haematochezia with tenesmus and mucus. Constricting lesions in the distal tract may also change the shape of the faeces passed. Other signs reported in either form include anorexia, [[diarrhoea]] and signs associated with acute intestinal obstruction or perforation and peritonitis.
+==Description==
+* No organism or chemical agent has been identified that will induce spontaneous intestinal adenocarcinoma.
+* The gross appearance of colorectal adenocarcinomas vary from pedunculated, particularly in the distal rectum, cobblestone, in particularly the middle rectum, or annular, also usually in the middle recutum, and may also have associations with tumour behaviour and prognosis.
+* In cats, adenocarcinomas have been reported to have been found in the ileum and ileocaecal region. Another study reports the jejunum to be the most common site.
+* Metastasis occurs via lymphatic and vascular routes. For small intestinal adenocarcinomas the most frequent sites of metastasis are the mesenteric lymph nodes. Other sites include the liver, kidneys, peritoneal cavity, omentum and lungs. Metastatic spread is commonly encountered at time of diagnosis.
+* Large intestinal adenocarcinomas often metastasise to the deep inguinal lymph nodes. The liver is less frequently affected. These tumours also undergo aggressive local growth and local recurrence after resection frequently occurs.
-Small intestinal adenocarcinomas may be palpable transabdominally as a mid-abdominal mass. Distended loops of small intestine may also be palpated, and rectal examination may reveal melaena. A mass may be palpated per rectum if it is large enough. This may present as a constriction or as nodular lesions protruding into the lumen. Bright red blood may be discovered on rectal examination.
-Various paraneoplastic syndromes have been associated with intestinal adenocarcinoma, including cutaneous disease and hyperviscosity syndromes.
+==Diagnosis==
+===Clinical Signs===
+Usually chronic and often dependent on the site of the tumour within the gastrointestinal tract and include:
+* For more proximal lesions:
+** vomiting
+* For lesions within the small intestine:
+** Weight loss
+* For tumours in the more distal tract:
+** Tenesmus
+** Hematochezia
+** Faeces may be altered in shape with constricting lesions
+* Other signs reported include:
+** Anorexia
+** Diarrhoea
+** Signs associated with acute intestinal obstruction (usually when the tumour has grown in an annular form), perforation and peritonitis
+Associated paraneoplastic abnormalities include:
+* Neutrophilic leukocytosis
+* Monocytosis
+* Eosinophilia
+* Cutaneous disease
+* Hyperviscosity syndromes
-Differential diagnoses for intestinal adenocarcinoma include: intestinal foreign body, [[Inflammatory Bowel Disease|inflammatory bowel disease]], alimentary lymphoma, gastrointestinal parasitism, leiomyoma or leiomyosarcoma and [[Pancreatitis|pancreatitis]].
+===Physical Examination===
+* An abdominal mass may be palpable
+* A rectal and potentially a lower colonic mass may also be palpable digitally via rectal examination
+* Cats may also be dehydrated
-===Laboratory Tests===
+===Haematology and Biochemistry===
+Abnormalities observed include:
+* Anaemia
+* Leukocytosis
+* Left shift
+* Monocytosis
+* Hypoproteinemia
+* Raised hepatic enzymes
+* High cholesterol
+* Raised BUN - may be due to concurrent renal insufficiency, dehydration or absorption following intestinal bleeding
+* Electrolyte abnormalities - due to intestinal obstruction
-Haematology often reveals a microcytic, hypochromic anaemia from chronic bleeding to the gastrointestinal tract. The loss of whole blood may also lead to hypoproteinemia on routine biochemistry. Electrolyte abnormalities may be seen with intestinal obstruction, and blood urea nitrogen may be raised due to absorption following intestinal bleeding or dehydration. A test for faecal occult blood may be positive.
+===Abdominal Radiography===
+* An abdominal mass may be visible with plain radiography
+* Alternatively evidence of obstruction may be observed
+* Poor serosal detail may be apparent
+* Contrast radiography can be useful for localising masses, revealing obstructions and filling defects and for intestinal areas more difficult to visualise via ultrasonography due to the accumulation of air.
-===Diagnostic Imaging===
+===Thoracic Radiography===
+This is highly advised though presentation with pulmonary metastasis is infrequent.
-It may be possible to visualise an abdominal mass with plain radiography, or dilated loops of small intestine may be seen, suggesting obstruction. Contrast radiography may be useful for localising filling defects of intraluminal space-occupying lesions or constrictions, particularly if gas accumulation makes ultrasonography difficult. Thoracic radiography is also recommended during diagnosis to detect pulmonary metastasis.
+===Abdominal Ultrasonography===
+Is more sensitive than radiography in localising a mass and can assess involvement of surrounding structures. In addition, guided needle aspiration or biopsy may be taken at this time. Findings may include the following:
+* Intestinal wall thickening with loss of wall layering - dogs with loss of layering are over 50 times more likely to have neoplastic disease rather than enteritis
+* In cats, adenocarcinomas have been described as being of mixed echogenicity and are often asymmetric
+* In dogs, adenocarcinomas have been described as being usually hypoechoic and most dogs had reduced gut motility
-Abdominal ultrasonography is more sensitive than radiography in localising a mass and can assess the involvement of surrounding structures. In addition, thickness and layering of the intestinal wall can be evaluated: dogs with loss of layering are over 50 times more likely to have neoplastic disease rather than enteritis. Canine intestinal adenocarcinomas usually appear ultrasonographically as hypoechoic masses, and affected dogs have reduced gut motility. In contrast, feline intestinal adenocarcinomas are typically of mixed echogenicity and are often asymmetric.
+===Endoscopy and Laparoscopy===
+Allow visualisation of the lesion. In addition, biopsies may be taken at this time. Open proctoscopes are more useful than fibreoptic scopes for colorectal lesions as direct visualisation of the mass is possible and deeper biopsies can be obtained. Nevertheless, often only small superficial samples can be obtained on biopsying the gut thus there can be significant variation in the interepretation of the findings.
-===Endoscopy===
+===Exploratory Laparotomy===
+Definitive diagnosis requires an excisional biopsy. All abdominal tissues should be assessed and full thickness biopsies taken. Resection of the mass and intestinal anastomosis may be performed at this time.
-As wells as permitting visualisation of the lesion, endoscopy allows biopsies of the mass to be taken. Open proctoscopes are more useful than fibre optic scopes for colorectal lesions as direct visualisation of the mass is possible and deeper biopsies can be obtained. Nevertheless, endoscopic biopsy obtains only small superficial samples and so there can be significant variation in the interpretation of the findings.
-===Biopsy===
-Ultrasound guided fine needle aspirate of the mass or an enlarged lymph node may yield neoplastic epithelial cells on cytology, ruling out lymphoma. Since tumours are often deep to the mucosal surface, endoscopic biopsy frequently does not provide adequate information to make a diagnosis. Therefore, exploratory laparotomy and a surgical biopsy are required for a definitive diagnosis.
 ==Treatment==
+===Surgery===
+Surgical excision is advised as primary treatment for intestinal adenocarcinoma. Extraserosal invasion or adhesions may cause difficulties and care must be taken to ensure there is no iatrogenic damage to the biliary and pancreatic ducts for duodenal lesions. In the small intestine, wide local resection (4-8cm margins) can usually be achieved via enterectomy and anastomosis. Stapling and suturing by hand have been shown to be equally efficient for this procedure. If appropriate regional lymph nodes should also be removed. Large margins may be more difficult to achieve for colorectal lesions due to access issues. Perioperative complications include peritonitis and sepsis.
-Surgical resection and anastomosis is the treatment of choice for both small and large intestinal adenocarcinoma. For small intestinal lesions, a margin of 4-8cm  is resected, and anastomosis may be achieved by suturing or stapling with no difference in outcome. Extraserosal invasion or adhesions may cause difficulties during resection and, for duodenal lesions, care must be taken to ensure there is no iatrogenic damage to the biliary or pancreatic ducts. Regional lymph nodes should be removed if there is evidence of metastasis. For colorectal adenocarcinomas, large margins may be more difficult to achieve due to restricted access. Transcolonic debulking is a palliative alternative for obstructive large intestinal lesions. For all types of surgery, postoperative complications include [[peritonitis]] and sepsis.
-Adjunctive chemotherapy in the form of doxirubicin has been shown to significantly improve survival times for cats with colonic adenocarcinoma, with median survival times improved from 56 to 280 days when doxorubicin treatment was used. No other evidence exists to confirm the benefits of adjuvant chemotherapy in dogs or cats. Piroxicam, a non-steroidal anti-inflammatory drug may have palliative effects for large intestinal and rectal lesions.
+===Adjuvant Chemotherapy===
+Doxirubicin has been shown to significantly improve survival times for cats with colonic adenocarcinoma with median survival times of 56 and 280 days for those not receving and those receiving chemotherapy respectively. No other evidence exists to confirm the benefits of adjuvant chemotherapy in dogs or cats. Piroxicam, a non-steroidal anti-inflammatory drug may have beneficial effects for rectal malignancy.
-The use of radiotherapy in intestinal adenocarcinoma has not been subject to detailed investigations due to the relative intolerance of the surrounding tissues to radiation. As well as the potential to cause intestinal perforations or adhesions, intestinal motility means that there is no certainty the same target will be irradiated each day. In a report of single high-dose irradiation used against a surgically-exposed anorectal tumour, no long-term side effects were observed.
+===Radiotherapy===
+Rarely reported due to concerns of intolerance of surrounding tissues leading to for example perforations and adhesions, in addition it cannot be relied upon that the same target will be irradiated each day due to intestinal mobility. There has been a report of single high-dose iradiation being used for anorectal adenocarcinomas which had been surgically exposed and no long-term side effects were observed.
-Stool softeners may be useful in cases where an annular tumour causes constriction of the bowel lumen.
 ==Prognosis==
+If no metastasis has occurred long term survival may be achieved following wide excision of a well differentiated small intestinal tumour. The rate of metastasis of adenocarcinoma to the local lymph nodes for both dogs and cats is approximately 50%. Without surgical intervention the mean survival of dogs with small intestinal adenocarcinoma is 12 days and reports varying from 114 days to 7-10 months with surgical treatment. Intensity of treatment is prognostic for colorectal tumours with palliative care carrying a poorer prognosis than local excision. In one study males with small intestinal adenocarcinoma had a significantly better prognosis than females with the same disease though the sample size was small. Local excision of colorectal adenocarcinoma has a median survival time of 22 months while the use of stool softeners alone has a median survival time of 15 months.
-If no metastasis has occurred long term survival may be achieved following wide excision of a well differentiated small intestinal tumour. The rate of metastasis of adenocarcinoma to the local lymph nodes for both dogs and cats is approximately 50%.
+There is significant perioperative risk associated with cats with small intestine adenocarcinoma with a high mortality rate within the first two weeks following surgery. However, after these two weeks long term control may be achieved. For cats with large intestinal adenocarcinoma survival time after surgery alone has been reported as approximately 4.5 months.
-In dogs, the overall prognosis is poor. Animals with pedunculated rectal adenocarcinomas have a better prognosis than other tumour locations or forms, but for all tumours many cases recur locally or experience metastasis. Without surgical intervention, the median survival of dogs with small intestinal adenocarcinoma is 12 days, and following resection this is improved to around 10 months. A pedunculated colorectal adenocarcinoma has a median survival time of 32 months after excision, but annular tumours have a much worse prognosis with a survival of around 1.6 months.
-There is significant perioperative risk associated with cats with small intestinal adenocarcinoma with a high mortality rate within the first two weeks following surgery. However, after these two weeks long term control may be achieved. For cats with large intestinal adenocarcinoma survival time after surgery alone has been reported as approximately 4.5 months, and survival of over one year has been reported in small intestinal cases.
-In order to track the progress of disease, it is recommended that animals undergo a full clinical examination, thoracic radiography and abdominal ultrasound at 1, 3, 6, 9 and 12 months post-surgery.
-==Links==
-*[http://www.vin.com/VINDBPub/SearchPB/Proceedings/PR05000/PR00130.htm| Proceedings of the World Small Animal Veterinary Association Congress 2001 - Update on Canine and Feline Gastrointestinal Neoplasia]
-* [http://www.merckvetmanual.com/mvm/index.jsp?cfile=htm/bc/23307.htm| The Merck Veterinary Manual - Gastrointestinal Neoplasia]
-{{Learning
-|Vetstream = [https://www.vetstream.com/canis/Content/Disease/dis00654.asp, Canine large intestinal neoplasia]
-|literature search = [http://www.cabdirect.org/search.html?q=title%3A%28intestine%29+AND+title%3A%28Adenocarcinoma%29 Intestinal Adenocarcinoma publications]
-}}
 ==References==
-* Liptak J. M, Withrow S.J. (2007) Cancer of the Gastrointestinal Tract, in '''Withrow and MacEwen's Small Animal Clinical Oncology, (Fourth Edition)''' ''Saunders Elsevier''.
+* Liptak J. M, Withrow S.J, (2007), Cancer of the Gastrointestinal Tract, in Withrow and MacEwen's Small Animal Clinical Oncology, fourth edition, Eds Withrow S.J, Vail D.M, Missouri, Saunders Elsevier, pp 491-501
-* Tilley, L.P. and Smith, F.W.K.(2007) '''The 5-minute Veterinary Consult (Fourth Edition)''' ''Blackwell Publishing''.
+* White, R. A. S, (2003), Tumours of the intestines, in BSAVA Manual of Canine and Feline Oncology, second edition, Eds Dobson J. M, Lascelles B. D. X, Gloucester, British Small Animal Veterinary Association, pp 229-233
-* White, R. A. S. (2003) Tumours of the intestines, in '''BSAVA Manual of Canine and Feline Oncology, (Second Edition)''' ''British Small Animal Veterinary Association''.
-{{review}}
-{{OpenPages}}
-[[Category:Intestines_-_Proliferative_Pathology]]
-[[Category:Intestinal Diseases - Dog]][[Category:Intestinal Diseases - Cat]]
-[[Category:Expert_Review]]