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Clinics of Oncology
Case Report ISSN: 2640-1037 Volume 5
Hüttemann E*
, Nagl S, Fleischmann C, Ebigbo A, Messmann H and Schnoy E
Internal Medicine III, University hospital Augsburg, Augsburg, Germany
Metastatic Colorectal Cancer in two Young Patients with Inflammatory Bowel
Disease – Relevance of Tight Endoscopic Surveillance Especially in Early-Onset
IBD and Review of the Literature
*
Corresponding author:
Eva Hüttemann,
Internal Medicine III, University Hospital
Augsburg, 86156 Augsburg, Germany,
Fax +49-821 400 2396; Tel: +49-821 400 2365;
E-mail: Eva.Huettemann@uk-augsburg.de
Received: 02 Oct 2021
Accepted: 12 Oct 2021
Published: 16 Oct 2021
Copyright:
©2021 Hüttemann E. This is an open access article distrib-
uted under the terms of the Creative Commons Attribution
License, which permits unrestricted use, distribution, and
build upon your work non-commercially.
Citation:
Hüttemann E, Metastatic Colorectal Cancer in two Young
Patients with Inflammatory Bowel Disease – Relevance of
Tight Endoscopic Surveillance Especially in Early-Onset
IBD and Review of the Literature.
Clin Onco. 2021; 5(5): 1-5
clinicsofoncology.com 1
Keywords:
Inflammatory bowel disease
1. Abstract
1.1. Background: The Risk of Colorectal Cancer (CRC) in In-
flammatory Bowel Diseases patients (IBD) is still higher than
in the general population. In this report, we present two cases of
early-onset and longstanding, highly active IBD (one patient with
Crohn`s Disease (CD), one patient with Ulcerative Colitis (UC)),
who developed metastatic CRC at a young age due to lack of sur-
veillance endoscopies and suboptimal medical treatment and cor-
relate our findings with available literature.
1.2. Case Report: In Case 1 a 35-year-old male patient with a
20-year history of CD presented with progressive abdominal pain,
nausea, and diarrhoea. In Case 2 a 31-year-old man with a 11-year
history UC presented with abdominal pain, an increased frequency
of bloody diarrhoea, weight loss and night sweats. Both suffered
from a CRC and died within a short time despite therapy.
1.3. Conclusion: In both cases, the primary risk factor that led to
CRC was severe, uncontrolled inflammation. Adequate treatment
and surveillance endoscopies may have prevented the develop-
ment of colorectal disease. Patients and their family care physi-
cians should be made more aware of possible disease complica-
tions, and patients should be referred to IBD specialized centers
where optimised and personalised treatment and surveillance strat-
egies can be initiated accordingly.
2. Introduction
Crohn`s Disease (CD) and Ulcerative Colitis (UC) are chronic In-
flammatory Bowel Diseases (IBD) with increasing incidences in
the last years [1-4]. Disease manifestation is usually between 20
and 30; however, disease onset can occur much earlier. Incidences
range between 0.4 – 22.9 per 100.000 patient-years and 2.3 – 44
per 100 000 patient-years for CD and UC, respectively. Clinical
symptoms can vary from asymptomatic to severe and recurrent
disease flares with bloody diarrhoea, weight loss, and abdominal
pain. While UC is predominantly found in the colon with procti-
tis, left-sided colitis, or pancolitis, CD can manifest in the entire
gastrointestinal tract, with so-called „skip lesions“. In addition, ex-
traintestinal manifestations, such as arthralgia, skin disorders, ocu-
lar manifestations, and Primary Biliary Cirrhosis (PSC), can occur.
Due to a better understanding of the underlying molecular path-
omechanism of IBD, various targeted therapies, including an-
ti-TNF drugs (infliximab, adalimumab, golimumab), anti-integ-
rine (vedolizumab), IL-12/IL-23 antibodies (ustekinumab), and
JAK-inhibitors (tofacitinib) have been developed for the treatment
of patients with CD and UC. This has led to effective control of in-
flammation, clinical remission, and long-term beneficial outcomes
with reduced surgery and fewer long-term complications [5-12].
According to the STRIDE criteria, the primary aim for patients
clinicsofoncology.com 2
Volume 5 Issue 5 -2021 Case Report
with IBD and acute inflammation is to achieve clinical response
and remission, followed by endoscopic improvement and remis-
sion („mucosal healing“) [13]. These aims and goals are associated
with the best long-term course and outcome. Especially for pa-
tients with UC, histologic remission might be superior to clinical
and endoscopic remission alone [14]. Despite optimised medical
therapies and treatment strategies, these treatment goals cannot
be achieved in all patients. Persisting inflammation and the extent
of colitis are confirmed risk factors for consecutive development
of complications such as stenosis, fistula, and Colorectal Cancer
(CRC).
The prognosis of CRC depends on the early detection of premalig-
nant lesions, but the risk of CRC in IBD patients is still higher than
in the general population [15]. Besides optimal medical treatment
strategies, endoscopic surveillance of patients with IBD is neces-
sary and is highly effective in reducing CRC incidence.
Although surveillance strategies to detect dysplastic lesions at an
early stage have been established, the risk for CRC may still be
underestimated in patients with early-onset IBD, whose initial
disease manifestation occurred at a young age. Furthermore, sur-
veillance endoscopies may not be offered to all patients at risk as
recommended in daily routine.
In this report, we present two cases of early-onset and longstand-
ing, highly active IBD (one patient with CD, one patient with UC),
who developed metastatic CRC at a young age due to lack of sur-
veillance endoscopies and suboptimal medical treatment and cor-
relate our findings with available literature.
3. Case 1
A 35-year-old male patient with a 20-year history of CD (first di-
agnosed at the age of 15) with a predominant manifestation at the
terminal ileum presented to our hospital with a 6-week history of
progressive abdominal pain, nausea, and diarrhoea. The last colo-
noscopy, which was performed about six years before presentation,
had revealed a highly active CD at the terminal ileum, with the in-
dication for biologics, e.g., anti-TNF therapy. However, due to the
subjective absence of symptoms, no intensive form of therapy was
initiated. Further surveillance endoscopies were not performed;
instead, his general practitioner repeatedly treated the patient with
steroids. On presentation in our emergency department at the end
of 2020, physical examination showed periumbilical pain, and lab-
oratory examination revealed signs of mild systemic inflammation
(white blood cell count: 15.8/nl, CRP 1,25 mg/dl) and microcytotic
hypochromic anaemia (Hb 91 g/l). The tumour cell marker CEA
was 68 ng/ml, and CA 19/9 was elevated at 9500 U/ml.
MRI enterography and Computed Tomography (CT) were per-
formed; both were highly suspicious of malignancy with intesti-
nal wall thickening of the ascending colon and cecum. Hepatic
and pulmonary metastases, as well as multiple suspicious lymph
nodes, were seen. Furthermore, severe rectosigmoid inflammation
with a blind-ending fistula and signs of a ileus in the terminal ile-
um were seen. Subsequent colonoscopy initially showed massive
inflammation of the ascending colon, cecum, sigmoid, and rectum.
However, histology showed only severe inflammation without
malignancy. Histopathological examination of the liver biopsies
revealed an adenocarcinoma, G2, Microsatellite Stability (MSS)
of the intestinal tract.
Two weeks later, the patient presented for systemic chemotherapy
but was in severely reduced general condition. He complained of
further weight loss and diffuse upper abdominal discomfort; food
intake was no longer possible. Chemotherapy was postponed be-
cause laboratory tests showed inflammation. Intravenous fluids
and antibiotics were administered. Due to clinical signs of ileus,
a CT scan of the abdomen was repeated. Mechanical small bowel
ileus in the area of the known coecal tumour was seen. The patient
subsequently underwent a palliative ileostomy. The postoperative
course was complicated by a high-output stoma and poor wound
healing. Chemotherapy was initiated according to the FOLFOX IV
regimen 2 weeks later.
The patient received palliative chemotherapy for two months but
developed an allergic reaction to oxaliplatin and new onset of hy-
percalcemia. An inpatient appointment for a second CT scan and
change of chemotherapy regimen was arranged for two days later.
CT showed massive progression of the primary tumour with the
development of multiple new metastases, including thoracic and
abdominal lymph node metastases as well as liver, adrenal, spleen,
umbilical, osseous, and pulmonary metastases. In addition, sub-
segmental pulmonary artery embolism in the right lower lobe was
described. The patient's general condition deteriorated rapidly. He
was transferred to the palliative care department, where he died of
tumour-associated multiple organ failure a few days later.
4. Case 2
A 31-year-old man with a past medical history of UC (pancolitis),
initially diagnosed in 2009, presented to the emergency depart-
ment for further evaluation of abdominal pain and an increased
frequency of bloody diarrhoea with a feeling of incomplete stool
emptying. The patient also complained of weight loss and night
sweats during the last weeks. His treatment regime from disease
onset included mesalazine, budesonide, and azathioprine. Two
years after the initial diagnosis, colonoscopy revealed persistent,
highly active pancolitis; however, the medication regime was not
optimised. Also, the patient had refused further regular colonosco-
pies due to uncomfortable experiences in the past.
When examined in our emergency department, he was found to
have local pain and a palpable resistance at the left lower abdo-
men. The white blood cell count was 14.54/nl, CRP was 13.87 mg/
dl, CEA 39 ng/ml, and CA 19/9 was elevated with 1900 U/ml.
The patient underwent colonoscopy, which revealed severe proc-
titis with suspicious areas of malignancy (Figure 1). Additionally,
Volume 5 Issue 5 -2021 Case Report
clinicsofoncology.com 3
there was stenosis at 20 cm, and endoscopic passage was not pos-
sible. Biopsies taken from these areas revealed adenocarcinoma of
the rectum and the sigmoid colon. Tumourdifferentiation was poor
(G3), with Microsatellite Stability (MSS), and BRAF wild type.
An abdominal CT scan confirmed a concealed perforated sigmoid
tumour and the presence of hepatic metastases. Emergency lap-
arotomy was not indicated due to the absence of an ileus at this
time. An ileostomy was intended after staging and preparation for
palliative chemotherapy had been completed. However, the patient
developed an acute abdomen, and tumour perforation was suspect-
ed. Laparotomy and Hartmann´s discontinuity resection with a ter-
minal stoma were performed. The patient developed postoperative
sepsis and was transferred to the Intermediate Care Unit (ICU)
where he received high-dose catecholamines, antibiotics, and vol-
ume substitution.
Further postoperative complications included poor wound healing,
constipation, and intraperitoneal fluid collection, which needed
external drainage. Histology showed adenocarcinoma with lymph
nodal metastasis and peritoneal carcinosis, pT3, p2Nb (8/15),
pM1, L1, V0, Pn1, local R1, G3, UICC IV. The first course of
palliative chemotherapy with 5-fluorouracil and irinotecan was
given without further complications. However, the patient was ad-
mitted with malaise, weight-loss, and poor general condition three
months later. A CT scan revealed massive progression of the liv-
er metastases with signs of liver failure and hyperbilirubinemia.
No further chemotherapy could be applied, and the patient was
referred to the palliative care department, where he passed away
four months after the initial diagnosis of metastatic CRC.
Figure 1A
Figure 1B
Figure 1: Endoscopy in a patient with UC after hospitalization. Stenosis
in the sigma due to massive tumour infiltration (figure 1 A), suspicious
rectal involvement macroscopically (figure 1B).
5. Discussion
In these two cases of early-onset IBD, high inflammation burden
and uncontrolled continuous inflammation over many years led to
the development of colorectal cancer with a lethal outcome in both
patients.
An association between CRC and IBD was first described in 1925.
10-15% of all-cause mortality in IBD is due to colon cancer [16].
The risk of developing colon cancer is comparable for UC and CD
[17]. Overall, the incidences reported in the literature vary widely.
The decreasing incidence in recent years can be attributed to bet-
ter control of inflammation with optimal medical treatment strat-
egies and tight endoscopic surveillance protocols. Despite more
intensive preventive measures, there still is an increased risk for
IBD patients to develop CRC. Compared to sporadic CRC, IBD
patients develop CRC 7.7 years earlier and have worse survival
rates. The colitis to CRC interval in the literature is given at 16 -21
years [18-21].
Known risk factors for the development of IBD-associated CRC
are long duration of disease, geographic characteristics for exam-
ple a north-south gradient, presence of strictures, PSC, and posi-
tive family history. Younger age at diagnosis is another indepen-
dent risk factor for CRC: 0–19-year old patients had a relative risk
of 43.8 %, while 20–39-year old patients had a relative risk of 2.65
%. Early-onset IBD leads to a potentially more prolonged duration
of disease [22-24]. Thus, the only modifiable risk factor is ade-
quate IBD therapy to achieve mucosal healing [25].
In case 1, IBD was diagnosed at 15 years of age and the time in-
terval between IBD diagnosis and CRC diagnosis was 20 years. In
case 2, on the other hand, a more aggressive course of disease than
described in the literature was observed. Although the initial diag-
nosis of UC was at 20 years of age, the colitis to CRC time interval
was only 11 years. In both cases, the primary risk factor that led
to CRC was severe, uncontrolled inflammation without adequate
medical therapy and endoscopic surveillance.
IBD-associated colonic carcinoma does not follow the usual ad-
enoma-carcinoma sequence as in sporadic carcinomas. From a
pathophysiological point of view, chronic inflammation plays
a central role in triggering dysplasia, and an inflammation-dys-
plasia-carcinoma sequence is thought to lead to more aggressive
growth and early development of metastatic disease [25, 26].
According to the current German guidelines, surveillance should
begin about 6-8 years after disease-onset to detect CRC ear-
ly. However, guidelines differ regarding screening intervals and
recommended techniques. While the American societies endorse
screening every 1-3 years, the European and Australian guidelines
recommend risk stratification for every patient after an index en-
doscopy [18, 27].
In addition to primary and secondary prevention, therapy adher-
ence and patient empowerment are essential aspects of disease
Volume 5 Issue 5 -2021 Case Report
clinicsofoncology.com 4
control. Patients must be educated about the link between IBD and
CRC, which is essential to guarantee adherence to treatment and
surveillance protocols. In a study of 156 patients with colitis, only
50% were aware of the correlation between their disease and CRC
[28, 29]. Unfortunately, surveillance endoscopies are still not of-
fered to all high-risk patients as recommended by the guidelines.
In both presented cases, it must be concluded that endoscopic sur-
veillance, medical therapy, and treatment adherence failed. Sub-
optimal therapy led to uncontrolled and severe inflammation over
many years. Screening colonoscopies were either not offered due
to lack of symptoms and underestimation of the disease or were
not accepted by the patient. In both cases, adequate treatment and
surveillance endoscopies may have prevented the development of
colorectal disease.
Finally, education of family care physicians and general practi-
tioners caring for IBD patients is necessary to improve adherence
to treatment and surveillance protocols. Patients and their family
care physicians should be made more aware of possible disease
complications, and patients should be referred to IBD specialized
centers where optimised and personalised treatment and surveil-
lance strategies can be initiated accordingly.
References
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clinicsofoncology.com 5
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Metastatic Colorectal Cancer in two Young Patients with Inflammatory Bowel Disease – Relevance of Tight Endoscopic Surveillance Especially in Early-Onset IBD and Review of the Literature

  • 1. Clinics of Oncology Case Report ISSN: 2640-1037 Volume 5 Hüttemann E* , Nagl S, Fleischmann C, Ebigbo A, Messmann H and Schnoy E Internal Medicine III, University hospital Augsburg, Augsburg, Germany Metastatic Colorectal Cancer in two Young Patients with Inflammatory Bowel Disease – Relevance of Tight Endoscopic Surveillance Especially in Early-Onset IBD and Review of the Literature * Corresponding author: Eva Hüttemann, Internal Medicine III, University Hospital Augsburg, 86156 Augsburg, Germany, Fax +49-821 400 2396; Tel: +49-821 400 2365; E-mail: Eva.Huettemann@uk-augsburg.de Received: 02 Oct 2021 Accepted: 12 Oct 2021 Published: 16 Oct 2021 Copyright: ©2021 Hüttemann E. This is an open access article distrib- uted under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and build upon your work non-commercially. Citation: Hüttemann E, Metastatic Colorectal Cancer in two Young Patients with Inflammatory Bowel Disease – Relevance of Tight Endoscopic Surveillance Especially in Early-Onset IBD and Review of the Literature. Clin Onco. 2021; 5(5): 1-5 clinicsofoncology.com 1 Keywords: Inflammatory bowel disease 1. Abstract 1.1. Background: The Risk of Colorectal Cancer (CRC) in In- flammatory Bowel Diseases patients (IBD) is still higher than in the general population. In this report, we present two cases of early-onset and longstanding, highly active IBD (one patient with Crohn`s Disease (CD), one patient with Ulcerative Colitis (UC)), who developed metastatic CRC at a young age due to lack of sur- veillance endoscopies and suboptimal medical treatment and cor- relate our findings with available literature. 1.2. Case Report: In Case 1 a 35-year-old male patient with a 20-year history of CD presented with progressive abdominal pain, nausea, and diarrhoea. In Case 2 a 31-year-old man with a 11-year history UC presented with abdominal pain, an increased frequency of bloody diarrhoea, weight loss and night sweats. Both suffered from a CRC and died within a short time despite therapy. 1.3. Conclusion: In both cases, the primary risk factor that led to CRC was severe, uncontrolled inflammation. Adequate treatment and surveillance endoscopies may have prevented the develop- ment of colorectal disease. Patients and their family care physi- cians should be made more aware of possible disease complica- tions, and patients should be referred to IBD specialized centers where optimised and personalised treatment and surveillance strat- egies can be initiated accordingly. 2. Introduction Crohn`s Disease (CD) and Ulcerative Colitis (UC) are chronic In- flammatory Bowel Diseases (IBD) with increasing incidences in the last years [1-4]. Disease manifestation is usually between 20 and 30; however, disease onset can occur much earlier. Incidences range between 0.4 – 22.9 per 100.000 patient-years and 2.3 – 44 per 100 000 patient-years for CD and UC, respectively. Clinical symptoms can vary from asymptomatic to severe and recurrent disease flares with bloody diarrhoea, weight loss, and abdominal pain. While UC is predominantly found in the colon with procti- tis, left-sided colitis, or pancolitis, CD can manifest in the entire gastrointestinal tract, with so-called „skip lesions“. In addition, ex- traintestinal manifestations, such as arthralgia, skin disorders, ocu- lar manifestations, and Primary Biliary Cirrhosis (PSC), can occur. Due to a better understanding of the underlying molecular path- omechanism of IBD, various targeted therapies, including an- ti-TNF drugs (infliximab, adalimumab, golimumab), anti-integ- rine (vedolizumab), IL-12/IL-23 antibodies (ustekinumab), and JAK-inhibitors (tofacitinib) have been developed for the treatment of patients with CD and UC. This has led to effective control of in- flammation, clinical remission, and long-term beneficial outcomes with reduced surgery and fewer long-term complications [5-12]. According to the STRIDE criteria, the primary aim for patients
  • 2. clinicsofoncology.com 2 Volume 5 Issue 5 -2021 Case Report with IBD and acute inflammation is to achieve clinical response and remission, followed by endoscopic improvement and remis- sion („mucosal healing“) [13]. These aims and goals are associated with the best long-term course and outcome. Especially for pa- tients with UC, histologic remission might be superior to clinical and endoscopic remission alone [14]. Despite optimised medical therapies and treatment strategies, these treatment goals cannot be achieved in all patients. Persisting inflammation and the extent of colitis are confirmed risk factors for consecutive development of complications such as stenosis, fistula, and Colorectal Cancer (CRC). The prognosis of CRC depends on the early detection of premalig- nant lesions, but the risk of CRC in IBD patients is still higher than in the general population [15]. Besides optimal medical treatment strategies, endoscopic surveillance of patients with IBD is neces- sary and is highly effective in reducing CRC incidence. Although surveillance strategies to detect dysplastic lesions at an early stage have been established, the risk for CRC may still be underestimated in patients with early-onset IBD, whose initial disease manifestation occurred at a young age. Furthermore, sur- veillance endoscopies may not be offered to all patients at risk as recommended in daily routine. In this report, we present two cases of early-onset and longstand- ing, highly active IBD (one patient with CD, one patient with UC), who developed metastatic CRC at a young age due to lack of sur- veillance endoscopies and suboptimal medical treatment and cor- relate our findings with available literature. 3. Case 1 A 35-year-old male patient with a 20-year history of CD (first di- agnosed at the age of 15) with a predominant manifestation at the terminal ileum presented to our hospital with a 6-week history of progressive abdominal pain, nausea, and diarrhoea. The last colo- noscopy, which was performed about six years before presentation, had revealed a highly active CD at the terminal ileum, with the in- dication for biologics, e.g., anti-TNF therapy. However, due to the subjective absence of symptoms, no intensive form of therapy was initiated. Further surveillance endoscopies were not performed; instead, his general practitioner repeatedly treated the patient with steroids. On presentation in our emergency department at the end of 2020, physical examination showed periumbilical pain, and lab- oratory examination revealed signs of mild systemic inflammation (white blood cell count: 15.8/nl, CRP 1,25 mg/dl) and microcytotic hypochromic anaemia (Hb 91 g/l). The tumour cell marker CEA was 68 ng/ml, and CA 19/9 was elevated at 9500 U/ml. MRI enterography and Computed Tomography (CT) were per- formed; both were highly suspicious of malignancy with intesti- nal wall thickening of the ascending colon and cecum. Hepatic and pulmonary metastases, as well as multiple suspicious lymph nodes, were seen. Furthermore, severe rectosigmoid inflammation with a blind-ending fistula and signs of a ileus in the terminal ile- um were seen. Subsequent colonoscopy initially showed massive inflammation of the ascending colon, cecum, sigmoid, and rectum. However, histology showed only severe inflammation without malignancy. Histopathological examination of the liver biopsies revealed an adenocarcinoma, G2, Microsatellite Stability (MSS) of the intestinal tract. Two weeks later, the patient presented for systemic chemotherapy but was in severely reduced general condition. He complained of further weight loss and diffuse upper abdominal discomfort; food intake was no longer possible. Chemotherapy was postponed be- cause laboratory tests showed inflammation. Intravenous fluids and antibiotics were administered. Due to clinical signs of ileus, a CT scan of the abdomen was repeated. Mechanical small bowel ileus in the area of the known coecal tumour was seen. The patient subsequently underwent a palliative ileostomy. The postoperative course was complicated by a high-output stoma and poor wound healing. Chemotherapy was initiated according to the FOLFOX IV regimen 2 weeks later. The patient received palliative chemotherapy for two months but developed an allergic reaction to oxaliplatin and new onset of hy- percalcemia. An inpatient appointment for a second CT scan and change of chemotherapy regimen was arranged for two days later. CT showed massive progression of the primary tumour with the development of multiple new metastases, including thoracic and abdominal lymph node metastases as well as liver, adrenal, spleen, umbilical, osseous, and pulmonary metastases. In addition, sub- segmental pulmonary artery embolism in the right lower lobe was described. The patient's general condition deteriorated rapidly. He was transferred to the palliative care department, where he died of tumour-associated multiple organ failure a few days later. 4. Case 2 A 31-year-old man with a past medical history of UC (pancolitis), initially diagnosed in 2009, presented to the emergency depart- ment for further evaluation of abdominal pain and an increased frequency of bloody diarrhoea with a feeling of incomplete stool emptying. The patient also complained of weight loss and night sweats during the last weeks. His treatment regime from disease onset included mesalazine, budesonide, and azathioprine. Two years after the initial diagnosis, colonoscopy revealed persistent, highly active pancolitis; however, the medication regime was not optimised. Also, the patient had refused further regular colonosco- pies due to uncomfortable experiences in the past. When examined in our emergency department, he was found to have local pain and a palpable resistance at the left lower abdo- men. The white blood cell count was 14.54/nl, CRP was 13.87 mg/ dl, CEA 39 ng/ml, and CA 19/9 was elevated with 1900 U/ml. The patient underwent colonoscopy, which revealed severe proc- titis with suspicious areas of malignancy (Figure 1). Additionally,
  • 3. Volume 5 Issue 5 -2021 Case Report clinicsofoncology.com 3 there was stenosis at 20 cm, and endoscopic passage was not pos- sible. Biopsies taken from these areas revealed adenocarcinoma of the rectum and the sigmoid colon. Tumourdifferentiation was poor (G3), with Microsatellite Stability (MSS), and BRAF wild type. An abdominal CT scan confirmed a concealed perforated sigmoid tumour and the presence of hepatic metastases. Emergency lap- arotomy was not indicated due to the absence of an ileus at this time. An ileostomy was intended after staging and preparation for palliative chemotherapy had been completed. However, the patient developed an acute abdomen, and tumour perforation was suspect- ed. Laparotomy and Hartmann´s discontinuity resection with a ter- minal stoma were performed. The patient developed postoperative sepsis and was transferred to the Intermediate Care Unit (ICU) where he received high-dose catecholamines, antibiotics, and vol- ume substitution. Further postoperative complications included poor wound healing, constipation, and intraperitoneal fluid collection, which needed external drainage. Histology showed adenocarcinoma with lymph nodal metastasis and peritoneal carcinosis, pT3, p2Nb (8/15), pM1, L1, V0, Pn1, local R1, G3, UICC IV. The first course of palliative chemotherapy with 5-fluorouracil and irinotecan was given without further complications. However, the patient was ad- mitted with malaise, weight-loss, and poor general condition three months later. A CT scan revealed massive progression of the liv- er metastases with signs of liver failure and hyperbilirubinemia. No further chemotherapy could be applied, and the patient was referred to the palliative care department, where he passed away four months after the initial diagnosis of metastatic CRC. Figure 1A Figure 1B Figure 1: Endoscopy in a patient with UC after hospitalization. Stenosis in the sigma due to massive tumour infiltration (figure 1 A), suspicious rectal involvement macroscopically (figure 1B). 5. Discussion In these two cases of early-onset IBD, high inflammation burden and uncontrolled continuous inflammation over many years led to the development of colorectal cancer with a lethal outcome in both patients. An association between CRC and IBD was first described in 1925. 10-15% of all-cause mortality in IBD is due to colon cancer [16]. The risk of developing colon cancer is comparable for UC and CD [17]. Overall, the incidences reported in the literature vary widely. The decreasing incidence in recent years can be attributed to bet- ter control of inflammation with optimal medical treatment strat- egies and tight endoscopic surveillance protocols. Despite more intensive preventive measures, there still is an increased risk for IBD patients to develop CRC. Compared to sporadic CRC, IBD patients develop CRC 7.7 years earlier and have worse survival rates. The colitis to CRC interval in the literature is given at 16 -21 years [18-21]. Known risk factors for the development of IBD-associated CRC are long duration of disease, geographic characteristics for exam- ple a north-south gradient, presence of strictures, PSC, and posi- tive family history. Younger age at diagnosis is another indepen- dent risk factor for CRC: 0–19-year old patients had a relative risk of 43.8 %, while 20–39-year old patients had a relative risk of 2.65 %. Early-onset IBD leads to a potentially more prolonged duration of disease [22-24]. Thus, the only modifiable risk factor is ade- quate IBD therapy to achieve mucosal healing [25]. In case 1, IBD was diagnosed at 15 years of age and the time in- terval between IBD diagnosis and CRC diagnosis was 20 years. In case 2, on the other hand, a more aggressive course of disease than described in the literature was observed. Although the initial diag- nosis of UC was at 20 years of age, the colitis to CRC time interval was only 11 years. In both cases, the primary risk factor that led to CRC was severe, uncontrolled inflammation without adequate medical therapy and endoscopic surveillance. IBD-associated colonic carcinoma does not follow the usual ad- enoma-carcinoma sequence as in sporadic carcinomas. From a pathophysiological point of view, chronic inflammation plays a central role in triggering dysplasia, and an inflammation-dys- plasia-carcinoma sequence is thought to lead to more aggressive growth and early development of metastatic disease [25, 26]. According to the current German guidelines, surveillance should begin about 6-8 years after disease-onset to detect CRC ear- ly. However, guidelines differ regarding screening intervals and recommended techniques. While the American societies endorse screening every 1-3 years, the European and Australian guidelines recommend risk stratification for every patient after an index en- doscopy [18, 27]. In addition to primary and secondary prevention, therapy adher- ence and patient empowerment are essential aspects of disease
  • 4. Volume 5 Issue 5 -2021 Case Report clinicsofoncology.com 4 control. Patients must be educated about the link between IBD and CRC, which is essential to guarantee adherence to treatment and surveillance protocols. In a study of 156 patients with colitis, only 50% were aware of the correlation between their disease and CRC [28, 29]. Unfortunately, surveillance endoscopies are still not of- fered to all high-risk patients as recommended by the guidelines. In both presented cases, it must be concluded that endoscopic sur- veillance, medical therapy, and treatment adherence failed. Sub- optimal therapy led to uncontrolled and severe inflammation over many years. Screening colonoscopies were either not offered due to lack of symptoms and underestimation of the disease or were not accepted by the patient. In both cases, adequate treatment and surveillance endoscopies may have prevented the development of colorectal disease. Finally, education of family care physicians and general practi- tioners caring for IBD patients is necessary to improve adherence to treatment and surveillance protocols. Patients and their family care physicians should be made more aware of possible disease complications, and patients should be referred to IBD specialized centers where optimised and personalised treatment and surveil- lance strategies can be initiated accordingly. References 1. Petritsch W, Fuchs S, Berghold A, Bachmaier G, Högenauer C, Hau- er AC, et al. Incidence of inflammatory bowel disease in the prov- ince of Styria, Austria, from 1997 to 2007: A population-based study. Journal of Crohn’s and Colitis. 2013; 7(1): 58-69. 2. Lucendo AJ, Hervías D, Roncero Ó, Lorente R, Bouhmidi A, Angue- ira T, et al. Epidemiology and temporal trends (2000-2012) of in- flammatory bowel disease in adult patients in a central region of Spain. Eur J Gastroenterol Hepatol. 2014; 26(12): 1399-407. 3. Ott C, Obermeier F, Thieler S, Kemptner D, Bauer A, Schölmerich J, et al. The incidence of inflammatory bowel disease in a rural region of Southern Germany: a prospective population-based study. Eur J Gastroenterol Hepatol. 2008; 20(9): 917-23. 4. Lophaven SN, Lynge E, Burisch J. The incidence of inflammatory bowel disease in Denmark 1980-2013: a nationwide cohort study. Aliment Pharmacol Ther. 2017; 45(7): 961-72. 5. Rutgeerts P, D’Haens G, Targan S, Vasiliauskas E, Hanauer SB, Pres- ent DH, et al. Efficacy and safety of retreatment with anti-tumor ne- crosis factor antibody (infliximab) to maintain remission in Crohn’s disease. Gastroenterology. 1999; 117(4): 761-9. 6. Colombel JF, Sandborn WJ, Rutgeerts P, Enns R, Hanauer SB, Panaccione R, et al. Adalimumab for maintenance of clinical re- sponse and remission in patients with Crohn’s disease: the CHARM trial. Gastroenterology. 2007; 132(1): 52-65. 7. Feagan BG, Schwartz D, Danese S, Rubin DT, Lissoos TW, Xu J, et al. Efficacy of Vedolizumab in Fistulising Crohn’s Disease: Ex- ploratory Analyses of Data from GEMINI 2. J Crohns Colitis. 2018; 12(5): 621-6. 8. Feagan BG, Rutgeerts P, Sands BE, Hanauer S, Colombel JF, Sand- born WJ, et al. Vedolizumab as induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2013; 369(8): 699-710. 9. Sandborn WJ, Feagan BG, Rutgeerts P, Hanauer S, Colombel JF, Sands BE, et al. Vedolizumab as induction and maintenance therapy for Crohn’s disease. N Engl J Med. 2013; 369(8): 711-21. 10. Sandborn WJ, Su C, Sands BE, D’Haens GR, Vermeire S, Schreiber S, et al. Tofacitinib as Induction and Maintenance Therapy for Ul- cerative Colitis. N Engl J Med. 2017; 376(18): 1723-36. 11. Sandborn WJ, Gasink C, Gao LL, Blank MA, Johanns J, Guzzo C, et al. Ustekinumab induction and maintenance therapy in refractory Crohn’s disease. N Engl J Med. 2012; 367(16): 1519-28. 12. Sands BE, Sandborn WJ, Panaccione R, O’Brien CD, Zhang H, Jo- hanns J, et al. Ustekinumab as Induction and Maintenance Therapy for Ulcerative Colitis. N Engl J Med. 2019; 381(13): 1201-14. 13. Turner D, Ricciuto A, Lewis A, D’Amico F, Dhaliwal J, Griffiths AM, et al. STRIDE-II: An Update on the Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) Initiative of the International Organization for the Study of IBD (IOIBD): Deter- mining Therapeutic Goals for Treat-to-Target strategies in IBD. Gastroenterology. 2021; 160(5): 1570-83. 14. Dal Buono A, Roda G, Argollo M, Peyrin-Biroulet L, Danese S. Histological healing: should it be considered as a new outcome for ulcerative colitis? Expert Opin Biol Ther. 2020; 20(4): 407-12. 15. Beaugerie L, Svrcek M, Seksik P, Bouvier AM, Simon T, Allez M, et al. Risk of colorectal high-grade dysplasia and cancer in a pro- spective observational cohort of patients with inflammatory bowel disease. Gastroenterology. 2013; 145(1): 166-75. 16. Stidham RW, Higgins PDR. Colorectal Cancer in Inflammatory Bowel Disease. Clin Colon Rectal Surg. 2018; 31(3): 168-78. 17. Baumgart DC. Endoscopic surveillance in Crohn’s disease and ul- cerative colitis: who needs what and when? Dig Dis. 2011; 29: 32-5. 18. Verdon C, Aruljothy A, Lakatos PL, Bessissow T. Endoscopic sur- veillance strategies for dysplasia in ulcerative colitis. Frontline Gas- troenterol. 2020; 11(2): 124-32. 19. Keller DS, Windsor A, Cohen R, Chand M. Colorectal cancer in in- flammatory bowel disease: review of the evidence. Tech Coloproc- tol. 2019; 23(1): 3-13. 20. Nadeem MS, Kumar V, Al-Abbasi FA, Kamal MA, Anwar F. Risk of colorectal cancer in inflammatory bowel diseases. Semin Cancer Biol. 2020; 64: 51-60. 21. Ahmadi AA, Polyak S. Endoscopy/surveillance in inflammatory bowel disease. Surg Clin North Am. 2007; 87(3): 743-62. 22. Yashiro M. Ulcerative colitis-associated colorectal cancer. World J Gastroenterol. 2014; 20(44): 16389-97. 23. Eaden JA, Mayberry JF. Colorectal cancer complicating ulcerative colitis: a review. 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  • 5. Volume 5 Issue 5 -2021 Case Report clinicsofoncology.com 5 25. Rabbenou W, Ullman TA. Risk of Colon Cancer and Recommended Surveillance Strategies in Patients with Ulcerative Colitis. Gastroen- terol Clin North Am. 2020; 49(4): 791-807. 26. Rogler G. Chronic ulcerative colitis and colorectal cancer. Cancer Lett. 2014; 345(2): 235-41. 27. Hata K, Kishikawa J, Anzai H, Shinagawa T, Kazama S, Ishii H, et al. Surveillance colonoscopy for colitis-associated dysplasia and cancer in ulcerative colitis patients. Dig Endosc. 2016; 28(3): 260-5. 28. Farrukh A, Mayberry JF. Surveillance for colorectal cancer and che- moprevention in ulcerative and Crohn’s colitis: The need for clinical strategies to increase effectiveness. JGH Open. 2019; 3(5): 370-3. 29. Low A, Love M, Walt R, Kane K, Eksteen B, Goh J. Understanding of chemoprophylaxis and concordance in inflammatory bowel dis- ease. World J Gastroenterol. 2010; 16(5): 578-82.