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is on ADV. Technological advances in ultrasonography such as high-frequency transvaginal scanning and three/four dimensional imaging have made first-trimester screening feasible [5]. We thus suggest early careful prenatal ultrasound screening after either maternal or paternal exposure to NUCs. Conflict of interest None declared. References [1] Marec F, Gelbic I. High recombinagenic activities of three antiviral agents, adenine derivatives, in the Drosophila wing spot test. Mutation Research 1994;311:305–17. [2] Lee JS, Mullaney S, Bronson R, et al. Transplacental antiretroviral therapy with 9-(2-phosphonylmethoxyethyl)adenine is embryotoxic in transgenic mice. Journal of Acquired Immune Deficiency Syndromes 1991;4:833–8. [3] Gilead Sciences. Hepsera package literature; 2009. http://www.accessdata. fda.gov/drugsatfda docs/label/2009/021449s016lbl.pdf [last accessed 26.12.13]. [4] Shapiro RL, Hughes MD, Ogwu A, et al. Antiretroviral regimens in pregnancy and breast-feeding in Botswana. New England Journal of Medicine 2010;362:2282–94. [5] Salomon LJ, Alfirevic Z, Bilardo CM, et al. Ultrasound in Obstetrics and Gynecology 2013;41:102–13.

Yuanyuan Gu Tong Ru Department of Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Nanjing University Medical School, Jiangsu, China Yi-Hua Zhou a,b Departments of Experimental Medicine and Infectious Diseases, Nanjing Drum Tower Hospital, Nanjing University Medical School, Jiangsu, China b Jiangsu Key Laboratory for Molecular Medicine, Nanjing University Medical School, Jiangsu, China a

a

Yali Hu a,b,∗ Department of Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Nanjing University Medical School, Jiangsu, China b Jiangsu Key Laboratory for Molecular Medicine, Nanjing University Medical School, Jiangsu, China ∗ Corresponding

author at: 321 Zhongshan Road, Nanjing 210008, China. Tel.: +86 25 8330 4616x66808; fax: +86 25 8310 5998. E-mail address: [email protected] (Y. Hu)

http://dx.doi.org/10.1016/j.dld.2014.08.035

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Adjuvant chemotherapy by FOLFOX for gastric hepatoid adenocarcinoma Dear Editor, A 63-year-old man was referred for epigastric pain and weight loss in March 2010. A gastroscopy was performed to investigate anaemia and revealed a large ulcerated antral tumour (Fig. 1A), and tumour biopsy samples established the diagnosis of a gastric hepatoid adenocarcinoma (HAC) (Fig. 1B). Both CEA and CA 19-9 were normal but the alpha fetoprotein (AFP) level was 2050 ng/ml. The patient underwent a subtotal gastrectomy. Histological analysis confirmed HAC diagnosis, pT2N1 (2N+/34N) M0. The patient received 9 cycles of adjuvant chemotherapy by simplified FOLFOX (oxaliplatin 85 mg/m2 , 5FU bolus 400 mg/m2 , 5FU 48 h infusion 2400 mg/m2 , D1 = D14) from May to October 2010. AFP decreased rapidly (from 2050 ng/ml in March 2010 before surgery to 48 ng/ml one month after surgery and has remained normal since June 2010). Repeat bi-annual computed tomography scans have shown no evidence of recurrence (last observation October 2013). Gastroscopy and upper endoscopic ultrasonography performed at 1-year followup were normal. In this case we observed curative treatment of gastric HAC with surgery and adjuvant FOLFOX chemotherapy. HAC is a rare variant of adenocarcinoma producing AFP and arising in extra-hepatic organs, with morphological similarity to hepatocellular carcinoma [1]. The prognosis is often poor and the best chemotherapy regimen is not established in this rare disease. In most cases, HACs are located in the stomach. The incidence of gastric HAC among gastric adenocarcinomas was reported to be 0.3–1%. The prognosis of HAC seems poorer than gastric adenocarcinoma without alpha fetoprotein elevation [2]. Treatment is mainly curative surgery when feasible for non-metastatic cancer. Currently there are no validated chemotherapy regimens for treatment of gastric HAC due to the low incidence of this tumour. For gastric adenocarcinoma FOLFOX chemotherapy showed a good efficacy in metastatic disease [3]. A recent case report showed no recurrence 3 years after surgical resection in peritoneal HAC and adjuvant FOLFOX chemotherapy [4]. In a series of three cases, one patient had a recurrence 5 months after resection of a pT2N0 gastric tumour and adjuvant oxaliplatin-based chemotherapy [5]. In the same study, two other patients with metastatic tumours were treated with oxaliplatinbased chemotherapy with contrasting outcomes. Nevertheless, our case suggests that chemotherapy with FOLFOX could be an option for this type of tumour as an adjuvant treatment. A larger series is needed to establish oxaliplatin efficacy in the adjuvant setting.

Fig. 1. (Panel A) Ulcerated antral tumour on upper endoscopy. (Panel B) Tumour was composed of solid hepatoid cells nests with abundant eosinophilic cytoplasm with centrally located large nuclei and obvious nucleoli.

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Conflict of interest None declared. References [1] Bourreille J, Metayer P, Sauger F, et al. Existence of alpha feto protein during gastric-origin secondary cancer of the liver. Presse Medicale 1970;78: 1277–8. [2] Su JS, Chen YT, Wang RC, et al. Clinicopathological characteristics in the differential diagnosis of hepatoid adenocarcinoma: a literature review. World Journal of Gastroenterology 2013;19:321–7. [3] Al Batran SE, Hartmann JT, Probst S, et al. Phase III trial in metastatic adenocarcinoma with fluorouracil, leucovorin gastroesophageal plus either oxaliplatin or cisplatin: a study of the Arbeitsgemeinschaft Internistische Onkologie. Journal of Clinical Oncology 2008;26: 1435–42. [4] Lucas ZD, Shah M, Trivedi A, et al. Hepatoid adenocarcinoma of the peritoneal cavity: Prolonged survival after debulking surgery and 5-fluorouracil, leucovorin and oxaliplatin (FOLFOX) therapy. Journal of Gastrointestinal Oncology 2012;3:139–42. [5] Ye MF, Tao F, Liu F, et al. Hepatoid adenocarcinoma of the stomach: a report of three cases. World Journal of Gastroenterology 2013;19: 4437–42.

Guillaume Velut Florence Mary Gastroenterology, Avicenne Hospital, HUPSSD, APHP, University Paris 13, Sorbonne Paris Cité, Bobigny, France Philippe Wind Surgery, Avicenne hospital, APHP, Université Paris 13, Sorbonne Paris Cité, Bobigny, France Thomas Aparicio ∗ Gastroenterology, Avicenne Hospital, HUPSSD, APHP, University Paris 13, Sorbonne Paris Cité, Bobigny, France ∗ Corresponding

author at: Gastroenterology and Digestive Oncology Avicenne Hospital, APHP, University Paris 13, Sorbonne Paris Cité 125 rue de Stalingrad, 93000 Bobigny, France. Tel.: +33 1 48 95 54 31; fax: +33 1 48 95 54 39. E-mail address: [email protected] (T. Aparicio)

http://dx.doi.org/10.1016/j.dld.2014.08.036

Weight loss outcomes after liver biopsy in patients with nonalcoholic fatty liver disease夽 Dear Editor, Nonalcoholic fatty liver disease (NAFLD) encompasses the entire spectrum of fatty liver disease in patients without significant alcohol intake, ranging from fatty liver to steatohepatitis and cirrhosis with prevalence estimates at 33% of the adult population affected [1]. In contrast to nonalcoholic fatty liver (NAFL) where no evidence of hepatocellular injury is seen on liver biopsy, the diagnosis of non-alcoholic steatohepatitis (NASH) is determined by hepatocyte ballooning, mixed acute and chronic inflammation, and collagen deposition on liver biopsy. NASH can develop into cirrhosis with eventual complications including liver failure and hepatocellular

夽 Disclaimer: The views expressed herein are those of the authors’ and do not necessarily reflect the official policy or position of the Department of the Navy, Department of Defense, or the U.S. Government.

carcinoma. Weight loss has been consistently shown to alter the natural history of NASH [2,3]. A weight loss of 5% is recommended to decrease steatosis and a 10% weight reduction is needed to improve hepatic necroinflammation. According to practice guidelines on the diagnosis and management of nonalcoholic fatty liver disease, a liver biopsy should be considered in patients with NAFLD who are at increased risk to have steatohepatitis and advanced fibrosis [4]. The clinician may pursue obtaining a liver biopsy to diagnose a patient with NASH given the potential clinical implications of this diagnosis. We sought to evaluate whether this practice of diagnosing NASH by liver biopsy leads to recommended weight loss outcomes in a “real world” clinical setting. We retrospectively evaluated patients older than age 18 referred to our medical centre for NAFLD between January 2008 and December 2010. This study was approved by our Institutional Review Board. Out of 255 patients, 64 individuals underwent a liver biopsy. NASH was diagnosed in the majority of patients who had a liver biopsy (84%). Twelve patients with NASH had advanced fibrosis on liver biopsy including one patient with cirrhosis. All patients diagnosed with NASH were counselled on the clinical implications of this diagnosis and on the importance of weight loss through proper nutrition and exercise. Despite this, only 50% lost any weight after 12 months. Patients with NAFL had a median net change in BMI of 1.24% (95% CI, −2.48 to 2.57) 12 months after their liver biopsy compared to a change in BMI of −0.64% (95% CI, −2.29 to 4.90) for those diagnosed with NASH (p = 0.512). After 12 months, the patients with NAFL had a median net change in BMI of 0.37 kg/m2 compared to a change in BMI of −0.175 kg/m2 for those diagnosed with NASH (p = 0.300). Only 1 patient diagnosed with NASH lost at least 10% of body weight 12 months after his liver biopsy which was after he underwent bariatric surgery. After being notified of biopsy results, patients with NASH who followed up with their gastroenterologist at least once in the office 12 months after biopsy had a median net decrease in BMI of −0.52 kg/m2 , compared to a net increase in BMI of 1.31 kg/m2 for those who did not follow up (p = 0.026). Diagnosing NASH by liver biopsy did not appear to significantly affect subsequent weight loss. Only one patient with NASH had reached the target weight loss of 10% and only half of patients diagnosed with NASH lost any weight in 12 months. There was no significant difference in weight loss between patients diagnosed with NAFL and those with NASH. To our knowledge, this is the first study to determine in a “real world” clinical setting if distinguishing NASH from NAFL by liver biopsy affects patient outcome and results in significant weight loss. While a liver biopsy may be obtained to diagnose NASH, this is not enough for patients to lose the recommended weight to affect clinical outcomes. After NASH is diagnosed, adequate follow up after diagnosing NASH may help increase weight loss compliance.

Conflict of interest None declared.

References [1] Browning JD, Sxczepaniak LS, Dobbins R, et al. Prevalence of hepatic steatosis in an urban population in the United States: impact of ethnicity. Hepatology 2004;40:1387–95. [2] Promrat K, Kleiner DE, Niemeier HM, et al. Randomized controlled trial testing the effects of weight loss on nonalcoholic steatohepatitis. Hepatology 2010;51:121–9. [3] Furuya Jr CK, de Oliveira CP, de Mello ES, et al. Effects of bariatric surgery on nonalcoholic fatty liver disease: preliminary findings after 2 years. Journal of Gastroenterology and Hepatology 2007;22:510–4. [4] Chalasani N, Younossiz Z, Lavine J, et al. The diagnosis and management of non-alcoholic fatty liver disease: practice guideline by the American