Letters to the Editor

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stomach and duodenum, requiring transfusions of 130 red blood cell (RBC) units between August 2011 and April 2012. Management of bleeding episodes was really complicated by the GT context and required the combination of numerous therapeutics: endoscopic treatments (epinephrine, sclerotherapy, endoclips, argon plasma coagulation), proton pump inhibitors, octreotide (Sandostatin LP), platelet transfusions, tranexamic acid, and embolization of the gastro-duodenal artery. These treatments proved inefficient to completely control the hemorrhages. Management of bleeding episodes required the concomitant administration of human leukocyte antigen (HLA) selected platelets (because the patient developed anti-HLA-I antibodies), recombinant activated factor VII (Novoseven) (24–80 perfusions of 90 μ g/ kg per bleeding episode), and tranexamic acid. Additionally, hormonal therapy (norethisterone 1 mg and ethinyl estradiol 35 μ g) was also implemented for a duration of 2 months in accordance with Coppola et al. (5). However, this treatment was stopped because of mastodynia and fear of thrombosis in a patient with several cardiovascular risk factors. Bevacizumab (Avastin, 5 mg/kg every 2 weeks for a total of six infusions) was introduced as a rescue therapy in April 2012: the patient experienced a new bleeding episode 2 weeks after the first bevacizumab infusion. No re-bleeding occurred during a 5-month period. But 3 months after the sixth bevacizumab infusion, a new recurrence requiring transfusion of 12 RBC units occurred in October 2012. Another course of six infusions (5 mg/kg every 2 weeks) was restarted in October 2012 followed by a maintenance treatment every 4 weeks, showing no re-bleeding after a 20-month follow-up. Anti-angiogenic drugs such as thalidomide may prevent the growth of vascular malformations and reduce the recurrence of GIADs (2,3). Unfortunately, thalidomide has significant side effects and can induce severe peripheral neuropathy (6). In our patient, who was also diabetic, we thus opted for bevacizumab because of its superior safety profile. Bevacizumab is an anti-VEGF humanized antibody, which has been approved for the treatment of © 2015 by the American College of Gastroenterology

colonic, renal, lung, ovarian, and breast cancer in conjunction with chemotherapy. Digestive perforations, re-bleeding, nosebleeds, and arterial thrombosis have been reported in association with chemotherapies in patients treated for neoplasia. Our patient experienced moderate epistaxis several times, occurring in a 24-h period following bevacizumab administration. More recently, bevacizumab was used successfully in HHT patients with recurrent epistaxis (7). Bevacizumab was also associated with decrease in cardiac output and reduced number of epistaxis episodes in patients with HHT and severe hepatic malformations (8). Finally, bevacizumab was used successfully as a rescue and maintenance treatment for severe gastro-intestinal bleeding in a patient with HHT (4). Because management of digestive angiodysplastic lesions is particularly difficult, bevacizumab should be considered as a therapeutic option or rescue therapy in patients with severe life-threatening bleeding, especially in the context of a severe hemostasis disorder such as GT. CONFLICT OF INTEREST The authors declare no conflict of interest. REFERENCES 1. Jackson CS, Gerson LB. Management of gastrointestinal angiodysplastic lesions (GIADs): a systematic review and meta-analysis. Am J Gastroenterol 2014;109:474–83. 2. Dabak V, Kuriakose P, Kamboj G et al. A pilot study of thalidomide in recurrent GI bleeding due to angiodysplasias. Dig Dis Sci 2008;53:1632–5. 3. Kamalaporn P, Saravanan R, Cirocco M et al. Thalidomide for the treatment of chronic gastrointestinal bleeding from angiodysplasias: a case series. Eur J Gastroenterol Hepatol 2009;21:1347–50. 4. Lupu A, Stefanescu C, Treton X et al. Bevacizumab as rescue treatment for severe recurrent gastrointestinal bleeding in hereditary hemorrhagic telangiectasia. J Clin Gastroenterol 2013;47:256–7. 5. Coppola A, De Stefano V, Tufano A et al. Longlasting intestinal bleeding in an old patient with multiple mucosal vascular abnormalities and Glanzmann’s thrombasthenia: 3-year pharmacological management. J Intern Med 2002;252:271–5. 6. Cavaletti G, Beronio A, Reni L et al. Thalidomide sensory neurotoxicity: a clinical and neurophysiologic study. Neurology 2004;62:2291–3. 7. Brinkerhoff BT, Poetker DM, Choong NW. Long-term therapy with bevacizumab in hereditary hemorrhagic telangiectasia. N Engl J Med 2011;364:688–9.

8. Dupuis-Girod S, Ginon I, Saurin J-C et al. Bevacizumab in patients with hereditary hemorrhagic telangiectasia and severe hepatic vascular malformations and high cardiac output. J Am Med Assoc 2012;307:948–55. 1

Hemostasis Unit, University Hospital, Grenoble, France; 2Gastroenterology Unit, University Hospital, Grenoble, France; 3Vascular Medical Unit, University Hospital, Grenoble, France. Correspondence: Raphael Marlu, MD, PhD, Haemostasis Unit, University Hospital, Boulevard Chantourne La Tronche, Grenoble 38700, France. E-mail: [email protected]

Response to Zoppini et al. Alice Fanin, MD1, Alberto Benetti, MD1, Ahmed Zakaria, PhD1, Valerio Ceriani, MD1 and Antonio E. Pontiroli, MD1 doi:10.1038/ajg.2014.420

To the Editor: We read with interest the original contribution by Zoppini et al. (1), because of the great number of subjects involved and the use of death certificates as a reliable source of information. Nevertheless, they claim some limitation, such as the follow-up duration (maximum 7 years) and the lack of data on diabetes type, treatment, and complications. We carried out a similar study, a prospective cohort recordlinked study, analyzing data of 969 morbidly obese (BMI >35 kg/m2) outpatients first visited in the period 1995–2001 (221 patients with diabetes mellitus type 2, 101 men and 120 women; 748 patients without diabetes, 222 men and 526 women); we collected clinical and pharmacological story, anthropometric data, and we completed a full panel of blood exams at baseline. Then, we evaluated the development of complications after a mean 15-year followup and, where applicable, mortality data. All these data were retrieved through the Lombardy Region Administrative Database, which lists death causes and exemptions; as described by Zoppini et al.(1), in Italy subjects with chronic diseases are entitled to free disease-specific care, and these patients are listed in a regional electronic database (2). In particular, we analyzed data regarding exemption for The American Journal of GASTROENTEROLOGY

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chronic liver disease (CLD) and for diabetes mellitus (DM). The same method was used to collect mortality data, according to ICD 10 classification. Our data showed at baseline that diabetic obese patients had hypertransaminasemia in a higher percentage of cases compared with nondiabetic obese patients (17.9% vs. 4.06%, P=0.0001 for aspartate aminotransferase and 55.5% vs. 34.1%, P=0.0001 for alanine aminotransferase); moreover, after a 15-year follow-up, diabetic subjects were more prone to develop an exemption for CLD than nondiabetic subjects (4.52% vs. 1.47%), regardless of aspartate aminotransferase and alanine aminotransferase levels at baseline. Mortality data were similar to those collected by Zoppini et al., with a higher mortality rate among diabetic patients, especially for neoplasia (11.3% vs. 2.6% P=0.001), followed by cardiovascular diseases (6.7% vs. 2.1%, P=0.0001), liver disease (2.7% vs. 0% P=0.0001), and renal (0.9% vs. 0%, P=0.05) and lung diseases (0.9% vs. 0.1%, P=NS). Although minding some limitations, our study’s strengths are the long follow-up period and the collection of patients’ complete information at baseline, which helps define patients at increased risk of comorbidities and mortality on the basis of anthropometric and blood examinations. Limitations are represented by the fact that in the exemption category for CLD, diseases different from NAFLD are also accounted for, and by the fact that we only examined obese patients. In conclusion, data of both studies confirm the idea of CLD as a long-term complication of diabetes mellitus, which cannot be predicted by physicians on the basis of blood exams. Therefore, liver diseases need to be directly investigated in all DM patients, in order to prevent evolution into cirrhosis, with a consequent greater mortality risk.

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population-based cohort study. Diabetes Care 2014;37:2225–32. 1

via A. Di Rudinì 9, Milano, Italy. Correspondence: Alice Fanin, MD, via A. Di Rudinì 9, Milano 20142, Italy. E-mail: [email protected]

Massive Hemorrhage from Unsuspected Pseudoaneurysm Within an Ulcer following “Roux-en-Y” Gastric Bypass Ankush Sharma, MD, MPH1, Roozbeh Houshyar, MD2, Rajesh Gulati, MD1 and Chandana Lall, MD2 doi:10.1038/ajg.2014.389

To the Editor: Obesity continues to be an epidemic in the United States (US), affecting over a third of the population. To date, Roux-en-Y gastric bypass (RYGB) has been proven to be the most effective interventional strategy for morbid obesity, and, depending upon the institution, is responsible for 62–80% of all bariatric surgeries in the US (1,2). While current guidelines recommend considering RYGB in patients with a body mass index (BMI) ≥40 kg/m2 or BMI ≥35 kg/m2 with one comorbid condition, newer studies suggest benefit

in patients with a BMI≥30 kg/m2 (2). Postoperative upper gastrointestinal bleeding (GI) after bariatric surgery is rare, but can be a fatal complication (1). To our knowledge, there have been no reported cases of pseudo-aneurysm formation in the gastric remnant leading to severe bleeding complications after Roux-en-Y gastrectomy. Here, we report this exact case. A 65 year female with a history of “Roux-en-Y” bypass 6 years earlier presented to the Emergency Department with severe abdominal pain, melena, and syncope. On physical examination, the patient was normotensive but tachycardic, with lethargy and mild abdominal distention. Lab workup was notable for a hemoglobin level of 5.9 g/dl and hematocrit of 19%, and iron studies were consistent with iron-deficiency anemia. The patient was thought to have a possible anastomotic ulcer, but both upper endoscopy and colonoscopy were unremarkable. Urgent double-balloon enteroscopy showed a 2-cm ulcer at the lesser curvature of the gastric remnant with a large adherent clot. This ulcer was not actively bleeding, but had a visible vessel, which was cauterized prophylactically. Despite enteroscopy, the patient continued to decompensate with signs of hypovolemic shock. Subsequent bleeding scans were negative, but computed tomography angiogram revealed a very large pseudoaneurysm within a deep ulcer crater at the remnant stomach near the previous surgical site, resulting in a large intraluminal hematoma (Figure 1).

CONFLICT OF INTEREST The authors declare no conflict of interest. REFERENCES 1. Zoppini G, Fedelli U, Gennario N et al. Mortality from chronic liver diseases in diabetes. Am J Gastroenterol 2014;109:1020–5. 2. Corrao G, Ibrahim B, Nicotra F et al. Statins and the risk of diabetes: evidence from a large

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Figure 1. Axial contrast-enhanced arterial-phase CT image through the upper abdomen demonstrates an area of active extravasation along the medial wall of the stomach (white arrow), and large intraluminal hematoma within the remnant stomach (black arrow).

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Response to Zoppini et al.

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