Marion Dhooge

Iron deficiency: From diagnosis to treatment

Iron deficiency is the most frequent cause of anaemia worldwide. It impairs quality of life, increases asthenia and can lead to clinical worsening of patients. In addition, iron deficiency has a complex mechanism whose pathologic pathway is recently becoming better understood. The discovery of hepcidin has allowed a better clarification of iron metabolism regulation. Furthermore, the ratio of concentration of soluble transferrin receptor to the log of the ferritin level, has been developed as a tool to detect iron deficiency in most situations. The cause of iron deficiency should always be sought because the underlying condition can be serious. This review will summarize the current knowledge regarding diagnostic algorithms for iron deficiency anaemia. The majority of aetiologies occur in the digestive tract, in men and postmenopausal women, and justify morphological examination of the gut. First line investigations are upper gastrointestinal endoscopy and colonoscopy, and when negative, the small bowel should be explored; newer tools such as video capsule endoscopy have also been developed. The treatment of iron deficiency is aetiological if possible and iron supplementation whether in oral or in parenteral form. New parenteral formulations are available and seem to have promising results in terms of efficacy and safety.

Early experience with a novel hemostatic powder used to treat upper GI bleeding related to malignancies or after therapeutic interventions (with videos)

Upper GI bleeding is a common clinical condition associated with considerable morbidity and mortality. Conventional treatment modalities, such as injection and thermal and mechanical therapies used alone or in combination, typically achieve hemostasis in more than 90% of cases. However, treatment of recurrent bleeding (necessary in 10%-30%) introduces additional limitations and adverse events. Epinephrine injection is associated with high rates of recurrent bleeding, and thermal therapies can cause tissue injury. Mechanical methods can be technically challenging and require specialized endoscopic expertise. These conventional modalities also can be challenging during treatment of diffuse, widespread bleeding. Peptic ulcer disease is the most common type of nonvariceal upper GI bleeding. However, bleeding also can occur as a consequence of therapeutic endoscopic interventions and from malignancies. In the latter, bleeding can be induced by tumor necrosis or chemotherapy and is typically diffuse and widespread. Even though conventional treatments can be effective as first-line therapies, hemostasis is often difficult to achieve and maintain

Sessile serrated adenoma: from identification to resection.

Until the past two decades, almost all colorectal polyps were divided into two main groups: hyperplastic polyps and adenomas. Sessile serrated adenomas presented endoscopic, pathological and molecular profiles distinct from others polyps. Previously under-diagnosed, physicians now identified sessile serrated adenomas. The serrated neoplastic pathway is accounting for up to one-third of all sporadic colorectal cancers and sessile serrated adenomas have been identified as the main precursor lesions in serrated carcinogenesis. By analogy with the adenoma-adenocarcinoma sequence, the sessile serrated adenomas-adenocarcinoma sequence, has been identified. The development of endoscopic resection techniques permits the consideration of a non-surgical approach as the first option regardless of the size of the lesion. Sessile serrated adenoma warrants the watchfulness of physicians and requires an optimal quality of the colonoscopy procedure, a thorough evaluation of the lesion, an adequate endoscopic resection and follow-up colonoscopies in accordance with sessile serrated adenomas guidelines. We herein present a review on sessile serrated adenomas focusing on their pathological specificities, epidemiology, treatment modalities and follow-up.

Feasibility of Gemcitabine plus Oxaliplatin in Advanced Hepatocellular Carcinoma Patients with Child-Pugh B Cirrhosis

Purpose: Sorafenib improves survival in advanced hepatocellular carcinoma (HCC), but the demonstration of its efficacy and safety is limited to Child-Pugh A cirrhotic patients. The biweekly combination of gemcitabine and oxaliplatin (GEMOX) is safe and widely used in patients with advanced malignancies. We aimed to evaluate the feasibility of GEMOX in HCC patients with Child-Pugh B cirrhosis ineligible for sorafenib. Methods: The medical records of cirrhotic patients with advanced HCC receiving the GEMOX regimen between July 2006 and November 2011 were retrospectively reviewed. Treatment was repeated every 2 weeks until disease progression or unacceptable adverse effects occurred. The primary evaluation criterion was safety. Secondary evaluation criteria were the presence of muscle wasting (sarcopenia), response rate, progression-free survival and overall survival (OS). Results: Patients with Child-Pugh A (group A, n = 17) or Child-Pugh B cirrhosis (group B, n = 15) received a total of 169 cycles (median 4, range 1–16/patient). Eight patients in each group had sarcopenia. Common toxicities were thrombocytopenia (25 and 14 in groups A and B, respectively; p = 0.65) and peripheral neuropathy (44 and 54% in groups A and B, respectively; p = 1). Neither febrile neutropenia nor toxic death occurred. One patient in each group experienced grade 3 oesophageal varices bleeding. The response and disease control rates were 18% (95% CI 0–35.8) and 58.8% (95% CI 35.4–82.2) in group A, and 27% (95% CI 4.3–49.1) and 60.0% (95% CI 35.2–84.8) in group B. The median progression-free survival and OS did not differ between the two groups, but median OS was significantly shorter in sarcopenic patients. Conclusions: The GEMOX regimen appears feasible in HCC patients with Child-Pugh B cirrhosis and exerts anti-tumour activity. These data need to be confirmed in a prospective study.

Reversible sarcopenia in patients with gastrointestinal stromal tumor treated with imatinib.

Imatinib 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.

Feasibility of gemcitabine and oxaliplatin in patients with advanced biliary tract carcinoma and a performance status of 2.

The use of gemcitabine and oxaliplatin is well documented in selected patients with advanced biliary tract carcinoma (BTC), but little is known on the feasibility of systemic treatments in patients with a performance status (PS) of 2. We retrospectively examined the medical records of consecutive BTC patients with a PS of 2 receiving gemcitabine 1000 mg/m2 plus oxaliplatin 100 mg/m2 every 2 weeks from January 2003 to December 2011 in our institution. Body composition was analysed by computed tomography scan to detect sarcopenia. The primary evaluation criterion was safety. The secondary evaluation criteria were the response rate, progression-free survival (PFS) and overall survival (OS). Twenty-eight patients (median age: 63 years, range 41–83) received a total of 175 cycles (median per patient: 6, range 2–12). Ten patients (35.7%) had sarcopenia on the pretreatment computed tomography scan. The most frequent toxicities were thrombocytopenia (grades 2–4: n=4, 14.3%), peripheral neuropathy (grades 2–3: n=9, 32.1%) and cholangitis (n=4, 14.3%). The best response was a partial response in 10.7% of patients [95% confidence interval (CI): 0–22.2] and stable disease in 42.9% of patients. The median PFS and OS were 4.6 (95% CI: 2.5–6.3) and 7.5 (95% CI: 5.2–9.5) months, respectively. The median PFS and OS were significantly longer in patients without sarcopenia: 7.0 months (95% CI: 4.4–8.0) vs. 2.2 months (95% CI: 2.0–2.5), P less than 0.01, and 10.4 months (95% CI: 7.5–11.6) vs. 4.9 months (95% CI: 3.7–5.2), P less than 0.01, respectively. In our experience, gemcitabine–oxaliplatin was feasible and induced effective palliation in PS2 patients with advanced BTC. Further studies are warranted to confirm these findings.

Diagnosis of Iron Deficiency in Inflammatory Bowel Disease by Transferrin Receptor-Ferritin Index.

AbstractIron deficiency is common in patients with inflammatory bowel disease (IBD), but can be difficult to diagnose in the presence of inflammation because ferritin is an acute phase reactant. The transferrin receptor-ferritin index (TfR-F) has a high sensitivity and specificity for iron deficiency diagnosis in chronic diseases. The diagnostic efficacy of TfR-F is little known in patients with IBD. The aim of the study was to assess the added value of TfR-F to iron deficiency diagnosis in a prospective cohort of patients with IBD.Consecutive IBD patients were prospectively enrolled. Patients were excluded in case of blood transfusion, iron supplementation, or lack of consent. IBD activity was assessed on markers of inflammation (C-reactive protein, endoscopy, fecal calprotectin). Hemoglobin, ferritin, vitamin B9 and B12, Lactate dehydrogenase, haptoglobin, and soluble transferrin receptor (sTfR) were assayed. TfR-F was calculated as the ratio sTfR/log ferritin. Iron deficiency was defined by ferritin <30 ng/mL or TfR-F >2 in the presence of inflammation.One-hundred fifty patients with median age 38 years (16–78) and Crohn disease (n = 105), ulcerative colitis (n = 43), or unclassified colitis (n = 2) were included. Active disease was identified in 45.3%. Anemia was diagnosed in 28%. Thirty-six patients (24%) had ferritin <30 ng/mL. Thirty-two patients (21.3%) had ferritin levels from 30 to 100 ng/ml and inflammation: 2 had vitamin B12 deficiency excluding TfR-F analysis, 13 of 30 (43.3%) had TfR-F >2. Overall, iron deficiency was diagnosed in 32.7% of the patients.TfR-F in addition to ferritin <30 ng/mL criterion increased by 36% diagnosis rates of iron deficiency. TfR-F appeared as a useful biomarker that could help physicians to diagnose true iron deficiency in patients with active IBD.

The predictive and prognostic value of the Glasgow Prognostic Score in metastatic colorectal carcinoma patients receiving bevacizumab.

The Glasgow Prognostic Score (GPS), based on C-reactive protein and albumin levels, has shown its prognostic value in metastatic colorectal carcinoma (mCRC) patients receiving conventional cytotoxic therapy. Bevacizumab, a monoclonal antibody to vascular epidermal growth factor, improves the overall survival in mCRC. The aim of the present study was to assess the prognostic value of GPS in mCRC patients receiving antivascular epidermal growth factor therapy. From August 2005 to August 2012, consecutive patients with mCRC who received chemotherapy plus bevacizumab were eligible for the present analysis. The clinical stage, C-reactive protein, albumin and the Eastern Cooperative Oncology Group performance status were recorded at the time of initiation of bevacizumab. Patients received 5-fluorouracil-based chemotherapy plus bevacizumab in accordance with the digestive oncology multidisciplinary staff proposal and in line with the French recommendations for the treatment of mCRC. Eighty patients were eligible (colon n=59, rectum n=21), with a median follow-up of 14 months (range 1–58 months). Chemotherapy given with bevacizumab and 5-fluorouracil was oxaliplatin (n=41, 51%) or irinotecan (n=27, 34%). At baseline, 56, 31 and 13% of patients had a GPS of 0 (n=45), 1 (n=25) and 2 (n=10), respectively. The median progression-free survival in these groups was 10.1, 6.5 and 5.6 months (P=0.16), respectively. The median overall survival was 20.1, 11.4 and 6.5 months, respectively (P=0.004). Our study confirmed the prognostic value of GPS in mCRC patients receiving chemotherapy plus bevacizumab. Given the poor survival observed in patients with an GPS of 2, studies dedicated to these patients could identify optimal treatment modalities.

A Rare Hematological Adverse Event Induced by Bevacizumab: Severe Thrombocytopenia

BACKGROUND Bevacizumab, a monoclonal antibody to vascular endothelial growth factor-A, is approved for the treatment of various malignancies, and its hematological toxicities are considered infrequent. METHODS A colorectal cancer patient receiving chemotherapy (5-fluorouracil and oxaliplatin) plus bevacizumab developed acute, severe thrombocytopenia. We postulated that this thrombocytopenia could be directly triggered by bevacizumab. RESULTS A man with stage IV colorectal cancer and synchronous liver metastasis had received 10 cycles of FOLFOX plus bevacizumab (5 mg/kg) without significant hematological toxicity. Due to thrombocytopenia, oxaliplatin was withdrawn after cycle 11. On cycle 12, shortly after bevacizumab infusion and before 5-fluorouracil infusion, the patient developed fever, lower limbs purpura, grade 1 proctorrhagia, and epistaxis. Platelets had decreased from 105,000/mm(3) to 3000/mm(3) within 1 hour after bevacizumab infusion. Flow cytometry identified platelet-associated immunoglobulins. Despite 2 apheresis-derived platelet transfusions, oral corticotherapy, and gamma globulin infusions, thrombocytopenia persisted, but was finally successfully treated with a peptibody thrombopoietin mimetic, which was introduced 28 days after the last bevacizumab infusion. CONCLUSIONS Clinicians should keep in mind that bevacizumab can induce acute and potentially severe immune-mediated thrombocytopenia.

Anti-epidermal or anti-vascular endothelial growth factor as first-line metastatic colorectal cancer in modified Glasgow prognostic score 2' patients.

In metastatic colorectal cancer, the modified Glasgow prognostic score (mGPS) has been approved as an independent prognostic indicator of survival. No data existed on poor prognosis patients treated with molecular‐targeted agents.