Systemic neo-adjuvant chemotherapy in metastatic colorectal cancer frequently causes morphological lesions involving hepatic microvasculature. Sinusoidal obstruction, complicated by perisinusoidal fibrosis and veno-occlusive lesion of the non-tumoral liver revealed by this study, should be included in the list of the adverse side-effects of colorectal systemic chemotherapy, in particular related to the use of oxaliplatin.

Histological tumor regression of HCRM to chemotherapy corresponds to fibrosis overgrowth and not to increase of necrosis. TRG should be considered when evaluating efficacy of chemotherapy for HCRM. Histological tumor regression was most common among oxaliplatin-treated patients and associated with better clinical outcome.

Pathologists should be aware of the distinctive lesions associated with OX and of their high prevalence. OX-related lesions are less frequent in patients treated with bevacizumab, suggesting that this drug has a preventive effect. Uniform criteria for diagnosis and grading of OX-associated lesions should help to include histological data in the optimal multidisciplinary management of CRLM.

A low preoperative platelet count and high APRI score seem to be the most reliable indicators to predict SOS severity.

Immune checkpoint inhibitors are monoclonal antibodies indicated for an increasing number of malignant diseases. These agents can cause specific side effects, which need to be anticipated while clear patterns of management need to be established. Immune checkpoint inhibitor-mediated gastrointestinal side effects, including diarrhea and colitis, occur in up to 30% of patients. Severe colitis can lead to severe dehydration or intestinal perforation. Endoscopic lesions and histopathological features of immune checkpoint inhibitor-induced colitis are similar to an inflammatory bowel disease (IBD) flare. Patients with immune checkpoint inhibitor-induced diarrhea and colitis are treated with corticosteroids. Infliximab can be used in cases of corticosteroid failure. Rectosigmoïdoscopy or colonoscopy should be performed when severe immune checkpoint inhibitor-induced colitis is suspected, but endoscopic investigations should not delay treatment. Specific patient education as well as co-operation between oncologists and gastroenterologists is essential.

Sinusoidal obstruction syndrome (SOS; formerly veno-occlusive disease) is a well-established complication of hematopoietic stem cell transplantation, pyrrolizidine alkaloid intoxication, and widely used chemotherapeutic agents such as oxaliplatin. It is associated with substantial morbidity and mortality. Pathogenesis of SOS in humans is poorly understood. To explore its molecular mechanisms, we used Affymetrix U133 Plus 2.0 microarrays to investigate the gene expression profile of 11 human livers with oxaliplatin-related SOS and compared it to 12 matched controls. Hierarchical clustering analysis showed that profiles from SOS and controls formed distinct clusters. To identify functional networks and gene ontologies, data were analyzed by the Ingenuity Pathway Analysis Tool. A total of 913 genes were differentially expressed in SOS: 613 being upregulated and 300 downregulated. Reverse transcriptase-PCR results showed excellent concordance with microarray data. Pathway analysis showed major gene upregulation in six pathways in SOS compared with controls: acute phase response (notably interleukin 6), coagulation system (Serpine1, THBD, and VWF), hepatic fibrosis/hepatic stellate cell activation (COL3a1, COL3a2, PDGF-A, TIMP1, and MMP2), and oxidative stress. Angiogenic factors (VEGF-C) and hypoxic factors (HIF1A) were upregulated. The most significant increase was seen in CCL20 mRNA. In conclusion, oxaliplatin-related SOS can be readily distinguished according to morphologic characteristics but also by a molecular signature. Global gene analysis provides new insights into mechanisms underlying chemotherapy-related hepatotoxicity in humans and potential targets relating to its diagnosis, prevention, and treatment. Activation of VEGF and coagulation (vWF) pathways could partially explain at a molecular level the clinical observations that bevacizumab and aspirin have a preventive effect in SOS.

Most drugs used for the treatment of solid tumors can induce hepatitis B reactivation in HBs antigen-positive patients. HBV screening can be recommended before systemic treatment initiation. Pre-emptive antiviral treatment can reduce the risk of HBV reactivation and prevent chemotherapy disruption.

BackgroundImatinib is a long-term, oral, targeted therapy for high-risk resected and advanced gastrointestinal stromal tumours (GIST). It is known that sarcopenia affects prognosis and treatment tolerance in patients with various solid cancers. We analysed lumbar skeletal muscle index changes in imatinib-treated GIST patients. Imatinib tolerance was also assessed to evaluate the influence of pre-treatment sarcopenia.MethodsThirty-one patients with advanced (n = 16) or high-risk resected (n = 15) GIST treated with imatinib (400 mg/day) were analysed retrospectively. Lumbar skeletal muscle indexes were evaluated on computed tomography images obtained before starting imatinib for all patients and at 6 months for those initially sarcopenic. Sarcopenia was defined using consensual cutoffs. Imatinib-induced toxicities were assessed after 3 months of administration.ResultsTwelve (38.7%) of the 31 patients were sarcopenic, including one unassessable at 6 months. Seven (63.6%) of the 11 assessable sarcopenic patients became non-sarcopenic after 6 months of imatinib. Pre-treatment sarcopenia was not associated with grades 3–4 toxicities, but the mean number of all-grade toxicities per sarcopenic patient was significantly higher for those non-sarcopenic (4.1 vs. 1.7, respectively, p < 0.01) after 3 months of treatment. Grades 1–2 anaemia and grades 1–2 fatigue were more frequent for sarcopenic than non-sarcopenic patients (83% vs. 26%, P < 0.01 and 42% vs. 5%, P = 0.02, respectively).ConclusionsSarcopenia is reversible in some GIST patients treated with imatinib. Pre-imatinib sarcopenia is predictive of non-severe toxicities, particularly anaemia and fatigue.