Case Report

Imaging side effects and complications of antineoplastic therapy in liver, pancreas and gastrointestinal tract- a pictorial review

Gina Al-Farra1* ; Dania Cioni2; E Neri2

1Senior consultant in oncoradiology, Dept. of Radiology, University Hospital of Herlev-Gentofte, Denmark.
2Master in Oncologic Imaging, Diagnostic and Interventional Radiology, Department of Translational Research, University of Pisa, Via Roma, 67, 56126 Pisa, Italy

Received Date: 15/12/2021; Published Date: 19/01/2022.

*Corresponding author: Gina Al-Farra, Senior consultant in oncoradiology, Department of Radiology, University Hospital of Herlev-Gentofte, Denmark.


Antineoplastic treatment can affect all organs and types of tissues, with manifestations that may appear acute or after prolonged treatment as a result of stochastic effects. Recognizing the side effects can have a big impact in the treatment itself but also save the patient's life, certain conditions can be life threatening ( for example, pneumonitis, infections, sinusoidal obstructive syndrome, etc.).Types of Cancer Treatment include Surgery, Chemotherapy, Radiation Therapy, Targeted Therapy, Immunotherapy, Stem Cell or Bone Marrow Transplant and Hormone Therapy.

Key points

Cancer treatments induce local and systemic changes on normal tissues,all cancer treatment modalities are associated with toxic effects (both short and long term).

During treatment complications can appear to be related to treatment but also cross-complications, often cancer patients have concomitant diseases.

Radiologists are tasked to differentiate expected findings from residual/relapse of tumors and cross complications.


Newer biologic drugs and immunomodulatory agents, as well as more tolerated and effective radiation therapy schemes have reduced treatment toxicity in oncology patients. The treatment are more precisely and personalized. However, although imaging assessment of tumor response is adapting to atypical responses like tumor flare, expected changes and complications of chemo/radiotherapy are still routinely encountered in post-treatment imaging examinations. Radiologists must be aware of old and newer therapeutic options and related side effects or complications to avoid a misinterpretation of imaging findings. Fast and highly performing CT and MRI technologies have opened new frontiers in oncology imaging, allowing tissue characterization, early diagnosis, prognostic evaluation, and accurate response assessment [1].

The table below lists the most well-known organ-related side effects associated with cancer treatment (surgery it is not included).

Table 1: Complications of Cancer Therapy Categorized by Affected Organ System.

Other complications are related to oncological intervention, from the simple drainage to complex treatments such as TACE, RF and Crio Ablation. It is absolutely essential to ensure that the patient's blood sample is within the permissive limits of intervention to avoid bleeding which is especially difficult to treat. The purpose of this review is to present the most common complications that may occur during antineoplastic treatment, while understanding that oncological imaging is actually a form of clinical radiology, conditioned by knowledge of various forms of treatment in oncology and their effects. The presentation includes explanation found on CT and a few MRI, these are used in the follow-up of cancer patients in our practice.

Cancer therapy induced hepatic toxicity

Chemotherapy-induced liver injury can present as hepatitis, steatosis, sinusoidal obstruction syndrome, and chronic parenchymal damages, molecular targeted therapy-associated liver toxicity ranges from mild liver function test elevation to fulminant life-threatening acute liver failure. Immune checkpoint inhibitors in oncology has given rise to immune-related adverse events, with differing mechanisms of liver toxicity and varied imaging presentation of liver injury. Highdose chemotherapy regimens for haematopoietic stem cell transplantation are associated with sinusoidal obstruction syndrome However, many chemotherapeutic agents and regimens are dosed based on the highest dose tolerated without toxicity.

Drug-induced liver injury (DILI) occurs as results of the main liver metabolic function, direct or secondary. The direct alterating of liver function is result that drugs are carried to the liver through either the systemic or portal circulations following absorption by the gastrointestinal tract. DILI occurs secondary to toxicity to hepatocyte and biliary ducts, alteration of lipid metabolism or damage to the hepatic vascular network.The end result of drug toxicity is injury to the hepatocytes in the form of mild to severe hepatitis and potential evolution to cirrhosis and fibrosis. Indirect toxicity occurs via altered lipid metabolism, which leads to deposition of fat within the liver, resulting in steatosis or steatohepatitis [2]. Druginduced vascular changes leads to liver injury in the form of sinusoid obstructive syndrome (SOS), portal vein thrombosis, and peliosis hepatis [3].


Drug-induced hepatitis can be categorised histologically into three forms: hepatocellular, cholestatic, or mixed but cannot be distinguished on imaging,can occur a few days after therapy start or weeks/month.

Various chemotherapeutic drugs have been associated with DILI, including asparaginase, intra-arterial 5-fluoro-uracil (FU), cyclophosphamide, 6mercaptopurine, high-dose methotrexate, paclitaxel, docetaxel, and cisplatin [4]. Besides conventional chemotherapeutic agents, MTTs, including vascular endothelial growth factor (VEFG) tyrosine kinase inhibitors (TKI), non-VEGF TKI, epithelial growth factor receptors (EGFR) inhibitors, and immune checkpoint inhibitors have been associated with acute hepatitis [2]. Essentially, chemotherapy drugs that can induce an acute hepatitis can likely cause hepatic necrosis. Mithramycin, an antitumor antibiotic, has been identified to be the most hepatotoxic to induce liver necrosis.

Reactivation of viral hepatitis has also been observed in patients treated with antineoplastic agents. Rituximab, alemtuzumab, and gemcitabine have been associated with reactivation of viral hepatitis B and C with percentages reaching 48% of cases in patients with hepatitis C undergoing treatment with rituximab [65].Imaging features of acute hepatitis include generalised hepatomegaly, perihepatic and pericholecystic fluid, gallbladder wall thickening (>3 mm), periportal reactive lymphadenopathy, and periportal oedema.On ultrasound, diffusely decreased parenchymal echogenicity with increased portal vein conspicuity (so-called “starry sky” appearance of the liver) has been reported in acute hepatitis but is insensitive.The most common finding is gallbladder wall thickening or oedema of the gallbladder fossa.Computed tomography (CT) or magnetic resonance imaging (MRI) shows diffusely decreased attenuation of the liver or diffuse T2-hyperintensity, with heterogeneous enhancement following contrast medium administration.CT imaging features of hepatitis with severity showed that gallbladder wall thickening >3 mm was associated with severe hepatitis and prolonged cholestasis.Choledochus thickening is seen associated with cholestasis.

Figure 1 : Imatinib induced acute hepatitis.Patient treated for metastatic gastrointestinal stromal tumour (GIST) with imatinib mesylate,presents with fever,abdominal pain.Coronal (a) and axial(b) enhanced CT shows periportal edema and small amount of free fluid. No infection focus was found except decreased attenuation around the portal system and at the hepatic hilum (periportal edema).Grade 3–4 liver toxicity could occur in one out of 40 treated patients with Imatinib for GIST.

Table 2: Hepatotoxicity according to drug agent and radiologic findings.

Steatosis and steatohepatitis

Fatty infiltration of the liver associated with chemotherapy it is known as CASH (chemotherapy-associated steatohepatitis) .CASH has been associated with 5-FU, associated with steatosis, and irinotecan, commonly associated with steatohepatitis. Tamoxifen and anastrozole, two hormonal agents utilised in oestrogen-receptorpositive breast cancer therapy, have been associated with steatosis seen in 14.6% of patients treated with anastrozole and in 41.1% of patients treated with tamoxifen [2, 4]. The imaging distinction among these entities CASH, NAFLD(Nonalkoholisk fedtleversygdom ) and hormone-related fatty liver disease is impossible, and the imaging features of steatosis and steatohepatitis frequently overlap.

Ultrasound demonstrates increased liver echogenicity,focal fat deposition or sparing may simulate a hepatic mass, but can be recognised by characteristic location, geographic shape, and absence of mass effect on vasculature. Moderate or severe fatty liver, defined as >33% of fat infiltration of hepatocytes documented by a liver biopsy, is detected by sonography with a sensitivity of 67–84% and specificity of 77– 100%.On unenhanced CT, observes reduced liver density, with hyperattenuation of vessels relative to the liver tissue, on contrast-enhanced CT, hepatic steatosis in moderate to severe cases can be diagnosed if absolute attenuation is <40 HU, with sensitivity and specificity of 86–87% [6, 7].

Figure 2: Liver steatosis induced by CAPOX, patient with disseminated colorectal cancer. Axial contrastenhanced CT image reveal fatty infiltration of the liver, reduced liver attenuation.Liver-spleen differentia lattenuation (liver minus spleen) cutoffs ranging from less than -20 to less than -43 HU on portal venous phase, depending on injection protocol, in this case HU liver 53 and spleen 104.

Veno-occlusive disease and sinusoidal obstruction syndrome (SOS)

SOS, also known as hepatic veno-occlusive disease, is an injury to the hepatic venous endothelium causing deposition of fibrous material within the venule walls and liver sinusoids leading to histological changes ranging from sinusoidal dilation to occlusion; SOS can progress to regenerative nodular hyperplasia.Preoperative neoadjuvant therapy for colorectal liver metastases (CRLM) is increasing in use and can lead to chemotherapy-induced damage to sinusoidal integrity.SOS is a rare complication of stem cell transplantation and has significant morbidity and mortality [8, 9]. On ultrasound ,which is the imaging modality of choice, which may show hepatomegaly ,portal vein abnormalities (dilatation,pulsatility,hepatofugal portal venous flow,elevated hepatic artery resistive index > 0.8), loss of triphasic hepatic venous flow ,gallbladder wall thickening (> 6-8 mm) ,ascites.On CT may be seen hepatomegaly, nutmeg liver,portal vein dilatation +/- portal thrombosis or perifere vein thrombosis,ascites. MRI with hepatocyte-specific contrast agent show a diffuse hypointense reticular pattern on post-contrast T1 delayed hepatobiliary phase as a highly specific sign for the diagnosis [8, 9].

Figure 3 : Folfirinox-induced sinusoid obstructive syndrome (SOS) in 69-year-old woman diagnosed with locally advanced pancreatic adenocarcinoma ,due to significant vascular involvement underwent FOLFIRINOX neoadjuvant chemotherapy.(a) Axial contrast-enhanced CT image demonstrates progressive changes in liver with heterogeneous hypo attenuation and patchy liver enhancement and perivascullary edema (b). Between scan a and b, and b and c (axial and d-coronal) it is a three-week interval, shows small and ill-defined intrahepatic arteries and decrease of hepatic parenchyma enhancement

Portal vein thrombosis

Portal vein thrombosis in cancer patients can occur as a hypercoagulable state associated with cancer; direct invasion of tumour into the portal vein, particularly common in patients with hepatocellular carcinoma; and as a complication of antineoplastic therapy.However, in adults, a few cases have been reported following chemotherapy treatment of L-asparaginase, autologous stem cell transplantation, and after haematopoetic cell transplantation [10]. There are not enough previous data on vascular events in association with 5fluorouracil alone, drug in use for more than 50 years and raises the possibility of trombotic event is more possible associated with bevacizumab and/or irinotecan treatment in colorectal cancer patients.The proposed mechanism of bevacizumabrelated thrombosis is complex-both hemorrhagic and thrombotic events may be involved. Briefly, bevacizumab by antagonizing VEGF’s functions might decrease the renewal capacity of endothelial cells in response to trauma, leading simultaneously to a tendency to bleeding and thrombosis [11].

Figure 4 : Chemotherapy-induced pseudocirrhosis. Patient with metastatic breast cancer,not responding to first line chemotherapy developed pseudocirrhosis 5 months after changing the treatment. Axial contrast-enhanced images from (a) baseline CT (change the treatment) and (b) follow-up CT demonstrate
development of multifocal capsular retraction with pseudocirrhosis appearance at end of treatment (EOT).

Chronic liver toxicity

Chronic DILI may manifest as hepatic steatosis, chronic hepatitis, or cirrhosis, usually secondary to intrahepatic cholestasis. Other forms of chronic hepatotoxicity include NRH (Nodular Regenerative Hyperplasia) and peliosis hepatis [12]. "Pseudocirrhosis" is a radiologic term used to describe the serial development of diffuse hepatic nodularity caused by chemotherapy for metastatic disease of the liver,seen in both metastatic breast and colon cancer, but it has also been reported in metastatic pancreatic cancer after gemcitabine and oxaliplatin therapy.In pseudocirrhosis changes in the liver parenchyma mimics liver cirrhosis, tumor tissue is retracted and scarring [19]. Furthermore, pseudocirrhosis may be associated with signs of portal hypertension,ascites, portosystemic collateral veins and splenomegaly. Changes are irreversible.

Postembolization Syndrome

Postembolization syndrome occurs in ~90% of patients following TACE, manifested by fever, malaise, right upper quadrant pain, nausea, and vomiting. Patients and their caregivers need to be apprised of this prior to TACE and provided with adequate analgesics and antiemetics for symptom control.Leung et al analyzed predictors of severe postembolization syndrome and found that gallbladder embolization and higher doses of chemoembolic agents correlated with prolonged postembolization syndrome [12, 13].

Hepatic abcess and biloma?

The pathophysiology of biloma formation involves ischemic injury to the peribiliary capillary plexus, which is supplied by branches of the hepatic artery. As a result, the integrity of the biliary tree is disrupted with subsequent biloma formation.Bacterial seeding of these bilomas can produce a hepatic abscess. Another mechanism is the development of an abscess within the necrotic center of a devascularized hepatic tumor. In either situation, patients who have chronic colonization of the biliary tree with enteric flora are at significantly higher risk of hepatic abscess formation [13].

Figure 5 : Biloma as complication after Radiofrecvens Therapy (RF), 35-yearold patient with cholangiocarcinoma and immune induced sclerosing cholangitis, complaints of pain below the right ribs, 2 weeks after treatment of liver metastasis in segment 5., shown on axial enhanced CT scan (a and b).MRI
is performed with specific liver contrast, the content of the accumulation has high T2w and low T1w signal. There is slightly increased signal on diffusionweighted sequences but no restriction in the accumulation (not shown her). It is thus considered most likely that it is a biloma and not an abscess. Low T1w signal speaks against hematoma. The accumulator has an outlet anterolateral along the puncture duct from the RFA procedure.

Figure 6 : Abcess as complication after TACE in liver .67 year old man known with HCC in cirrhotic liver,has received 4.TACE treatment, after one week admitted in hospital with abcess in segment 4/8 ,Klebsiella pneumonia, enterobacter cloacae and streptococcus anginosus in the drain fluid.Axial enhanced CT image reveal well circumscribed slightly peripherally enhancing, centrally hypoattenuating lesion with gas.Treated with drain (not shown on this image).

Hepatic Artery Injury

Tortuous anatomy and congenital anatomic variations in the hepatic arteries may require extensive catheter manipulation to enable access to the target artery. Advancement of a catheter against resistance or without a sufficient length of leading guide wire can produce arterial spasm, dissection, or thrombosis [14].

Radiation-Induced Liver Disease

Liver Injury from External Beam Radiation:

Radiation induced liver disease (RILD) after conventionally fractionated radiotherapy was first described several decades ago, and it was soon thereafter recognized to have the histopathologic features of sinusoidal of venoocclusive disease (VOD), currently termed sinusoid obstructive syndrome (SOS) [15].The clinical scenario commonly called “classic” radiation induced liver disease (RILD) occurs typically within 4 months after hepatic radiation therapy. It is characterized by anicteric ascites and hepatomegaly and an isolated elevation in alkaline phosphatase disproportionate to that of other liver enzymes. “Classic” RILD is unlikely to occur after a mean liver dose of approximately 30 Gy in conventional fractionation [15-17].

Pancreas changes under cancer treatment

Acute pancreatitis

Chemotherapy-induced pancreatitis is well documented in the literature and is associated with chemotherapeutic agents as L-asparaginase, carboplatin cisplatin, cytarabine, ifosfamide, paclitaxel, tretinoin, and vinorelbine.The onset of pancreatitits range from hours to 1 month after drug administration [18,19]. Nitsche et al[ 80] believe that the overall incidence of drug-induced pancreatitis may be between 0.1% and 2%. Pancreatitis is an uncommon but severe complication of TACE. The incidence of this complication is rare, reported in only 1.7 % of TACE patients, and may occur because of reflux of chemoembolic agents to the pancreas [21].

For detecting and grading the severity of acute pancreatitis, multi-detector computed tomography (MDCT) is the modality of choice. Chemotherapeutic agents first cause acute interstitial pancreatitis, which may further progress to acute necrotising pancreatitis. On CT, acute interstitial pancreatitis may be characterised by fluid collections, peripancreatic fat stranding, focal areas of decreased attenuation, or diffuse oedema within the pancreas [22].

Figure 7 : Pancreatitis on Axial enhanced CT Scan, localised edema around the head of pancreas (b) about 1 month after induced antineoplastic therapy with Gemcitabin og Nab-Paclitaxel + Nivolumab. Axial enhanced CT scan (a) at the start of treatment shows tumor in the head of pancreas and clear peripancreatic fat tissue.

Pancreatic atrophy and cysts

Pancreatic atrophy is a possible adverse effect of cancer therapy. In the literature, it has been reported that long-term use of sorafenib is correlated with pancreatic atrophy. Ganten et al. explored the relationship between extended sorafenib therapy and pancreatic atrophy and reported a mean pancreatic volume loss of 25 % in hepatocellular carcinoma patients being treated with long-term sorafenib [23].

Atrophy is detectable as soon as 3 months after initiation of sorafenib therapy but may not present until as late as 2–3 years following treatment [24]. Pancreatic atrophy can be best detected using CT and is often accompanied by fatty infiltration of the pancreas.Other pancreatic changes that have been observed include fatty replacement of pancreatic tissue over the course of cancer therapy and cystic changes in the pancreas,the evidence of the relationship of these findings to specific agents is lacking in the literature [22].

Figure 8 : 80-year-old male with relaps of colon cancer treated with bevacizumab og 5-FU. a -Axial contrast-enhanced CT after 36 month chemotherapy shows marked pancreatic atrophy as well as fatty replacement findings. b - Axial contrast-enhanced CT before initiation of chemotherapy.

Biliary system

Acute acalculous cholecystitis, biliary inflammation , biliary sclerosis and biliary stasis

Gallbladder inflammation related to cancer therapy has a growing evidence in literature associate to use of targeted therapeutic agents with acute acalculous cholecystitis, particularly everolimus and sunitinib [25]. Tirumani et al. examined the use of molecular-targeted therapies (sunitinib, bevacizumab, everolimus, and sorafenib) and associated gallbladder complications and found acute cholecystitis in 66 % of patients with variable onset between 2 weeks and 5 months [26]. These patients ultimately required dose reduction, temporary discontinuation of the therapy, or permanent discontinuation of the therapy with 50 % requiring either cholecystectomy or cholecystotomy [26]. Biliary excretion of certain oncologic agents may cause changes in the biliary epithelium leading to biliary enhancement on imaging. Common chemotherapeutic agents that are excreted through the bile include L-asparaginase, doxorubicin, epirubicin, and paclitaxel [27]. Excretion of these therapeutic agents may have adverse effects on the epithelium causing irritation, thickening, and inflammation, which can be visualised as enhancement on CT and MR imaging. Chemotherapy-induced biliary sclerosis (CIBS) is a well-known toxicity associated with hepatic arterial infusion pump chemotherapy (HAIPC) with floxuridine [28]. Chemotherapeutic agents can cause CIBS through adverse toxicity on the biliary system or ischaemic changes to the pericholangitic venous plexus, leading to stricture of the biliary ducts [29]. Biliary stasis has been noted after initiation of tamoxifen and doxorubicin, bile cannot be excreted from the liver into the duodenum and causes subsequent formation of biliary sludge and biliary dilatation [29].

Complications of oncological therapy in the gastrointestinal system

Chemotherapy and targeted therapy complications

Chemotherapy-induced gastrointestinal (GI) complications may occur at any stage during cancer treatment. Its exact incidence is currently unknown. Targeting highlymitotic cells, chemotherapeutic agents may prove cytotoxic to a variety of rapidlydividing, though non-neoplastic tissues. Such tissues are present in the GI tract, potentially resulting in mucosal inflammation, ulceration, and perforation. This direct cytotoxicity may be further compounded by the predisposition to infection, a result of chemotherapy-induced immune-suppression and failure to mount a leucocytosis in response. The majority of chemotherapeutic agents induce mucositis, nausea, vomiting, and diarrhoea as a result, most often mild, self-limiting occurrences that may be empirically-managed.Most common cause of diarrhea is dysbacteriosis,chemotherapy and other drugs has effects on intestinal microbial flora. Nonetheless, the risk of more severe adverse-effects such as typhlitis, enterocolitis, infective colitis, perforation, GI haemorrhage, ischaemic colitis, and obstruction is very real and may require aggressive management and resuscitation [32]. Cross-sectional imaging in the form of CT is the most rapid, widely-available technique for such investigation, if possible enhanced.The clinical presentation and radiological manifestations of chemotherapeutic complications are considerable in consensus.The radiologically findings are for sure important and may potentially improve treatment decision,whether or not the patient needs surgery or just medication.

Gastritis, duodenitis and gastric and duodenal ulceration can be seen in patients receiving hepatic arterial infusion chemotherapy of fluorodeoxyuridine. This has been described in the literature and is thought to be related to malpositioning of the catheter tip in the gastroduodenal artery rather than the hepatic artery [33].

PIPAC (Pressurized IntraPeritoneal Aerosol Chemotherapy) is a new treatment option in patients with peritoneal carcinomatosis. With PIPAC, chemotherapy is administered directly at the target organ (peritoneum), leading to a high tissue concentration of chemotherapy, without systemic uptake and thereby minimizing side effects. Transient abdominal pain might be explained by the chemical peritonitis induced by PIPAC with oxaliplatin. Some of the patients experienced reversible urinary retention, properly due to pain and the chemical peritonitis induced by PIPAC, sporadic nonspecific pains in the upper abdomen. Classical sideeffects of systemic chemotherapy such as mucositis, nausea/ vomiting, diarrhea, paresthesia, cutaneous symptoms and alopecia were not reported by the patients.

Figure 9 : PIPAC induced chemical peritonitis .Axial contrast-enhanced CT image demonstrates duodenal surface edema (a) and peritoneal enhancement (b) after PIPAC treatment of patient with disseminated ovarian cancer

Neutropenic enterocolitis is one of the few oncological emergencies. The diagnostic criteria include neutropenia (neutrophil count less than 1 cell/μl); temperature greater than 38.3 °C and evidence for colitis (diffuse abdominal pain and distension, watery diarrhoea, vomiting, GI haemorrhage). This entity is most likely to occur 5–14 days after commencement of chemotherapy, during the leucocytic nadir. Pathological features of affected bowel include mucosal and transmural oedema, haemorrhage, ulceration, necrosis, and perforation. Neutropenic enterocolitis and typhlitis are the most common GI side effects of chemotherapy and are encountered in association with a number of regimes including paclitaxol, taxotere, platinum-based regimes, and cytosine arabinoside [34, 35]. The term “typhlitis” refers to neutropenic enterocolitis of the caecum, with the caecum and ascending colon to variable degrees involved. Typhlitis was originally described in children with acute leukaemia undergoing chemotherapy and is most often encountered in association with leukaemia or lymphoma. More recently typhlitis has been reported in patients with solid tumours, such as non-small cell lung, ovarian, and peritoneal cancer [36]. This condition has also been described in immunosuppressed patients without cancer, such as kidney transplant patients, and those with cyclical neutropenia, aplastic anaemia, and acquired immunodeficiency syndrome (AIDS) [35]. CT findings on cross-sectional enhanced imaging shows the bowel wall diffusely thickened or edematous, mucosal hyperemia and mucosal ulceration. Pericolonic fat stranding and submucosal bleeding is also seen. Transmural bowel wall involvement with necrosis, pneumatosis and less commonly perforation can also be seen later on. Prompt diagnosis with conservative treatment using antibiotics is used in patients when early diagnosis is made

Figure 10 : Neutropenic necrotizing colitis in 35 years hematologic patient treated with stem cell transplant 10 days earlier. Non enhanced CT , axial (a, b) and coronal pictures (c)demonstrates wall thickening of the entire colon, fat stranding, small amount free fluid and submucosal diffuse bleeding.

Pseudomembranous colitis is seen often related to antibiotic or chemotherapeutic administration as results of replacement of “normal” gut flora and colonization by C. difficile. C difficile produces both a cytotoxin and enterotoxin, resulting in colonic inflammation, diarrhea, and characteristic pseudomembranous exudates. Clinical findings may be absent or range from mild self-limiting diarrhea to fulminant colitis requiring colectomy. CT manifestations of pseudomembranous colitis include mural thickening (up to 3 cm), low-attenuation mural thickening corresponding to mucosal and submucosal edema, the “accordion sign” (interdigitating of orally-administered contrast between the edematous low attenuation haustral folds, giving the appearance of alternating bands of high and low attenuation), the “target sign” (“double halo sign”; intense mucosal enhancement occurring due to mucosal hyperemia and juxtaposed to low attenuation mural edema), mural enhancement, colonic dilatation, pericolonic stranding, thickening of fascial planes, and ascites. The degree of wall thickening is generally greater than in other inflammatory or infectious forms of colitis (often >10 mm) and is classically diffuse in distribution. Distribution may vary considerably, leading to diagnostic uncertainty, involvement ranging from focal segmental rectal thickening to pan colonic abnormality .In one – third of cases there are normal found on CT [37-40].

Enteritis-Chemotherapy-related diarrhea (CRD) is most commonly described with fluoropyrimidines (particularly fluorouracil [FU] and capecitabine) and irinotecan. Diarrhea is the dose-limiting and major toxicity of regimens containing a fluoropyrimidine with irinotecan. However, in addition to conventional cytotoxic drugs, many molecularly targeted agents (including tyrosine kinase inhibitors [TKIs] and monoclonal antibodies) are also associated with CRD. Direct ischemic mucosal damage is reported in patients treated with agents targeting the vascular endothelial growth factor (VEGF), while an immune-mediated colitis is responsible for diarrhea with immune checkpoint inhibitors [41, 42]. The typical appearance of enteritis on CT images illustrates submucosal edema and hyperemia of the mucosa and serosa.

Figure 12 :  Irinotecan induced enterocolitis. Patient with metastatic colon cancer, had been undergoing treatment with Irinotecan for approximately 8 moth. Patient complained of abdominal pain during the course of therapy, with newonset diarrhea. Axial (a) and coronal (b) contrast-enhanced CT image through the abdomen reveals bowel wall thickening.

Ulceration, perforation og GI hemorrhage-oncological GI perforation may occur in one of a number of scenarios: spontaneous tumor rupture (particularly primary GI tumors, infiltrating tumors, or infiltrating adenopathy), neoplastic ulceration, tumor necrosis occurring secondary to therapy, drug-induced perforations, and inflammatory conditions. GI lymphomas, in particular, are associated with perforation or bleeding related to regression of the primary tumor during appropriate chemoradiotherapeutic therapy [43, 44]. Other medications commonly coadministered with antiplatelet therapy such as nonsteroidal anti-inflammatory drugs (NSAIDs), oral anticoagulants, and corticosteroids are also known to increase the risk of ulceration and GI bleeding. Concomitant use of these medications and antiplatelet therapy might increase the risk of UGIB [45].

Ileus and obstruction

Paralytic ileus is associated with infections or disorders of autonomic neuropathy caused by chemotherapy drugs, such as vincristine and vinblastine or opioid, which depress bowel peristalsis. Paralytic ileus has been recognised as a potential side effect of capecitabine with an estimated incidence of 4% to 6% [46]. The pathophysiology of capecitabine-induced paralytic ileus is not well understood. Information regarding fluoropyrimidines and their effect on the enteric motor system is scant. It can be speculated that 5FU metabolites may play a role in causing paralytic ileus because of the association between 5FU metabolites and peripheral neuropathy [47]. Ileus is seen as focal or diffusely dilated bowel without evidence of an obstructing mass ( carcinosis ) .Bowel obstruction seen on CT shows dilated loops of bowel proximal to the obstruction, with distinct transition point, a normal caliber or collapsed bowel distally. As above, small bowel obstruction has been associated with vincristine and bevacizumab [48]. If bowel vessels are involved, they can give rise to critical ischemic events, which lead to necrosis and perforation. Thrombotic and thromboembolism events pathogenesis is induced by drug-related endothelial damage, with consequent basement membrane exposure and abnormal coagulation cascade activation [48].

Mesenteric infarction and pneumatosis

Mesenteric infarction leads indirect to bowel damage and it is related to thromboembolic events, arteriel thrombosis is less frequent and intestinal ischemia is a rare complication in cancer patients treated with chemotherapy [110]. Thrombotic and thromboembolism events pathogenesis is induced by drug-related endothelial damage, with consequent basement membrane exposure and abnormal coagulation cascade activation [49, 51]. Platinum-based chemotherapy regimens are responsible for higher thromboembolism risk, but not other vascular events; this risk is superimposable between cisplatin and carboplatin [52]. Molecular target agents can increase thrombotic risk: thalidomide, an immunomodulatory and antiangiogenetic drug commonly used in multiple myeloma therapy, has shown thromboembolic events raise, anti-VEGFR and anti-VEGF targeted agents as bevacizumab, sorafenib and sunitinib are responsible to arterial thrombotic events increase, because of their role in endothelial integrity regulation probably. Thromboembolisms and vasculitis caused by immune checkpoint regulators such as anti-PDL1 seem to be rare events [53, 54, 55]. CT is the gold standard to diagnose pathological bowel features in the emergency setting because it allows detection of vascular anatomy and secondary signs of mesenteric ischemia, with high sensitivity and specificity (82–96% and 94%, respectively [56, 57].

Figure 13 : CAPOX(capecitabine-oxaliplatin combination)induced panniculitis/infarction .Patient with duodenal cancer, Whipple operation before 2 years ago, in treatment with CAPOX, complains on painfull right lumbar zone. CT axial demonstrate Whipple operation, (a) and diffuse localized infiltration of
mesenterium in right side (b).


Pneumatosis intestinalis (PI) is defined as bowel wall gas that presents as submucosal or subserosal cysts,ranging from benign conditions to fulminant diseases. PI is a radiological finding and not a diagnosis. It is usually diagnosed by plain abdominal radiography or CT scanning, but it could also be documented by MRI and ultrasonography. The presence of mesenteric stranding, bowel wall thickening and dilatation, ascites and confinement of the intramural gas to the small bowel. PI confined to the right colon is more frequently benign, whereas the presence of pneumoperitoneum is nearly always associated with every case of PI [58]. A variety of conditions and treatments can lead to this complication, including chemotherapy. PI is an uncommon complication of chemotherapy, but it should be considered in any cancer patient who presents with vague gastrointestinal or obstructive symptoms. Chemotherapeutic agents reported to induce PI are cyclophosphamide, cytarabine, docetaxel, irinotecan, cisplatin, fluorouracil, and bleomycin.

Gastrointestinal toxicity of radiation therapy [59].

Risk Factors for predisposing to Radiation Injury

Treatment-related risk factors

Higher radiation doses

Higher volume of irradiated small bowel

Extended- or opposed-field radiation techniques

Short-course radiotherapy

Postoperative chemo radiotherapy

Concurrent administration of chemotherapy

Patient-related risk factors



Inflammatory bowel disease (Crohn disease, UC)

Connective tissue disorders (SLE, scleroderma, polymyositis, dermatomyositis, excluding RA)

Heavy smoking (at least one pack per day)

Abnormally low BMI (< 18.5)

Previous abdominal or pelvic surgery

Genetic predisposition (AT heterozygotes)

(AT = ataxia-telangiectasia; BMI = body mass index; RA = rheumatoid arthritis; SLE= systemic lupus erythematosus; UC = ulcerative colitis.)

Gastrointestinal toxicity can occur following irradiation of thoracic, abdominal, or pelvic malignancies, gastrointestinal structures are often located within the radiation therapy (RT) field. These toxicities can limit the maximum tolerated dose of RT and chemotherapy and thus may limit the efficacy of treatment. Acute toxicities refer to those with onset during or shortly after the course of treatment. Late toxicities are those occurring after three months after completion of RT. These often reflect the spectrum of radiation tissue changes that can be lasting and irreversible [59]. The incidence and severity of RT side effects depend upon the site, volume of tissue exposed, and treatment schedule, including total dose, dose per fraction, and type of radiation. Other risk factors for radiation induced GI toxicity include the use of concomitant chemotherapy.

Radiation esophagitis

Symptoms of acute radiation esophagitis include dysphagia, odynophagia, and substernal discomfort. Patients with late toxicity often present with dysphagia secondary to stricture or altered motility caused by fibrosis/muscular damage or nerve injury or odynophagia due to chronic ulceration [9, 60]. In patients with acute radiation esophagitis, double-contrast esophagograms may reveal a variable segment of esophageal narrowing with multiple discrete ulcers or a distinctive granular appearance of the mucosa within a known radiation portal. The majority of patients with esophagitis had abnormalities on CT, including a thickened esophageal wall (≥5 mm) in 55% and a target sign in 17%. Although barium studies and endoscopy are more sensitive modalities for detecting this condition, the CT finding of a relatively long segment of circumferential esophageal wall thickening, with or without a target sign, should suggest the diagnosis of esophagitis in the proper clinical setting [61].

Radiation gastritis

Acute radiation gastritis can cause nausea and vomiting within 24 hours after the start of treatment. Symptoms generally resolve within one to two weeks following completion of RT. Manifestations of late radiation gastritis include abdominal pain due to nonulcer dyspepsia, gastric ulcers, and antral stenosis [59, 62]. Radiation gastritis usually occurs 2-9 moth after the initial radiotherapy. The dose at which 5% of patients develop complications at 5 years, when the entire stomach is irradiated, is estimated to be 50 Gy. Small doses of radiation (up to 15 Gy) cause reversible mucosal damage, whereas higher doses cause irreversible damage with atrophy and ischemic-related ulceration [63, 64]. CT may demonstrate nonspecific gastric wall thickening along with stranding in the perigastric fat, especially in acute fase , radiation gastritis it is better demonstrate with barium studies .Ulcers are typical seen in acute fase and cannot be differentiated from benign ulcer disease.

Radiation enteritis

The small intestine is very radiosensitive, it is relatively mobile and radiationinduced changes are therefore less common than might otherwise be expected. Symptoms of acute radiation enteritis include diarrhea, abdominal pain, nausea and vomiting, anorexia, and malaise. Radiation-induced diarrhea often appears during the third week of treatment and typically disappears two to six weeks after the completion of RT. Late effects include malabsorption and diarrhea. Patients may have bloating, excessive gas, and borborygmi due to small intestinal bacterial overgrowth. Other symptoms include bleeding or abdominal pain due to ulceration, and fever secondary to abscess formation. Patients with severe disease may develop intermittent, partial, or complete small bowel obstruction due to strictures [59, 65, 66]. In acute and subacute radiation enteritis, barium studies of the small intestine often show nodular filling defects or thumb printing. Changes similar to those of intestinal ischemia may result from arteriolar obliteration. The most frequent manifestation of chronic radiation enteropathy is submucosal thickening of the bowel wall. Focal areas of narrowing and long-segment strictures may develops. In some cases, bowel obstruction occurs as a result of the strictures or of adhe- sions. Fistulas may also develop [59, 65, 66, 67].

Radiation proctitis

The incidence of radiation proctitis is not clear due to the lack of consensus on its definition and reporting methodologies. There is a general agreement that the incidence is likely related to the dose of radiation, area of exposure, method of delivery, and the use of cytoprotective agents. The doses generally delivered to the pelvis vary from 45 to 50 Gy for adjuvant or neoadjuvant treatment for prostate or anorectal malignancies; up to 90 Gy is considered the definitive therapy for gynecological malignancies [68]. It is generally agreed that treatments <45 Gy cause very few side effects. Doses between 45 and 70 Gy, which is the dosage range for most treatments, cause more complications, but the complications tend to be of lesser intensity .Doses above 70 Gy cause significant and long standing injury to the surrounding area[68].

CT may demonstrate acute radiation injury findings such as bowel wall edema and enhancement of the mucosa with contrast . Chronic changes of radiation injury to the pelvis structures include thickening and increased density of the perirectal fat, fascia, and rectal wall and fibrosis between the sacrum and rectum. Edema and enhancement of the mucosa are no longer present in the chronic phase of injury. MRI may demonstrate increased signal uptake indicative of inflammatory changes as well as a characteristic pattern of varying edema .However, both CT and MRI can fail to differentiate between postradiation changes and recurrent malignancy

Figure 14 : Radiation induced proctitis and colitis as side effect after analcancer treatment with RT.Chronic radiation-induced enteropathy in a 63-year-old woman, 2 years after ended treatment, axial contrastenhanced CT scan (a) and MRI (b) shows diffuse thick walls to the rectosigmoid colon, no haustrae and fibrosis in bowl wall.

Anal toxicity

The anal canal is typically spared from significant radiation exposure but it may be affected if radiation therapy (RT) is used to treat anal, low rectal, or gynecologic cancers. Acute anal toxicity is relatively common, and its incidence is increased with concurrent chemotherapy or large RT fraction size .It presents as a perianal skin reaction that ranges from minimal skin changes to moist desquamation and erythema. Late complications of RT can appear months to years after completion of therapy and include anorectal ulceration, anal strictures or stenosis, and anorectal fistulas. Patients with late anal radiation toxicity usually present with anal pain and anal incontinence [67, 68].

CT findings includes increased density but blurred appearance of the subcutaneous fat , with common cords, mesh intervals, thickened mesenteric vessels, blurred edges, swollen pelvic wall muscles and blurred muscle borders. MRI is most sensitive to show fibrosis and narrowing, fat changes and necrosis.

Figure 15 : Radiation induced proctitis as side effect after analcancer treatment with RT.Aksial MRI, T1w (a) before treatment shows almost circumferencial anal tumour.One year after ended RT, control MRI scan, T1w axial (b) and coronal (c) shows fibrosis in anal canal and infiltration of the fat tissue, fat infiltration of pelvis bone

Figure 3 : Folfirinox-induced sinusoid obstructive syndrome (SOS) in 69-year-old woman diagnosed with locally advanced pancreatic adenocarcinoma ,due to significant vascular involvement underwent FOLFIRINOX neoadjuvant chemotherapy.(a) Axial contrast-enhanced CT image demonstrates progressive changes in liver with heterogeneous hypo attenuation and patchy liver enhancement and perivascullary edema (b). Between scan a and b, and b and c (axial and d-coronal) it is a three-week interval, shows small and ill-defined intrahepatic arteries and decrease of hepatic parenchyma enhancement


The broad spectrum of cancer treatment and technological improvements, including CT-guided and MRI-guided planning, IMRT, particle therapy combined with better diagnostic imaging provides the opportunity for decrease the risk of acute and late toxicity .The complications related to treatment can only be clinical without radiological findings but for the most part there is the possibility of radiological support to confirm unexpected events during the treatment. Awareness of cancer therapy-induced toxicities is important for all oncologists but to recognize the complication which can be life threatening, do the oncologic imaging an important part of the patient's disease course and treatment.


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