J Clin Gastroenterol
Letters to the Editor
however, it has biases and is mainly used in research studies.5 Magnetic resonance imaging (MRI) has been proven to be accurate in detecting fat in the liver.6,7 MRI-determined proton density fat fraction (MRI-PDFF) is a novel technique that reduces the biases seen with MRS and has been shown to be highly correlated with MRS.8,9 It has been demonstrated that MRI-PDFF is accurate in quantifying liver fat.8,10 We recently showed that MRI-PDFF correlates highly with MRS in quantifying liver fat in patients enrolled in a clinical trial for nonalcoholic steatohepatitis.8 In contrast to MRS, MRI-PDFF is easier to apply, requires less time, is cheaper compared with MRS, and is now commercially available.7 Although underutilized, the fat fraction quantification is available on MR machines. Thus, we propose the use of MRI and, in particular, MRI-PDFF, as an alternative to CT scans and US in NAFLD diagnosis. This will allow for accurate quantification of liver fat and will be a useful tool for longitudinal follow-up. The cost of MRI is traditionally known to be higher than US. However, MRI-PDFF does not require contrast and can be performed in a short time. Indeed, Medicare data show an insignificant difference in price of this limited MRI in comparison with US.7 We do not believe that it is useful to expose patients to additional radiation by performing a CT scan when US imaging has already been shown to be uninformative and a more accurate means of diagnosing NAFLD is readily available. Mazen Noureddin, MD Cyrus Khoyilar, BS Suzanne L. Palmer, MD Department of Medicine, Division of Gastrointestinal and Liver Diseases (for Noureddin and Khoyilar), Department of Radiology (for Palmer) USC Keck School of Medicine Los Angeles, CA
REFERENCES 1. Review Team, LaBrecque DR, Abbas Z, Anania F, et al. World Gastroenterology Organisation global guidelines: nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. J Clin Gastroenterol. 2014;48:467–473. 2. Bohte AE, van Werven JR, Bipat S, et al. The diagnostic accuracy of US, CT, MRI and 1 H-MRS for the evaluation of hepatic steatosis compared with liver biopsy: a meta-analysis. Eur Radiol. 2011;21:87–97. 3. Limanond P, Raman SS, Lassman C, et al. Macrovesicular hepatic steatosis
352 | www.jcge.com
4.
5.
6.
7.
8.
9.
10.
in living related liver donors: correlation between CT and histologic findings. Radiology. 2004;230:276–280. Mottin CC, Moretto M, Padoin AV, et al. The role of ultrasound in the diagnosis of hepatic steatosis in morbidly obese patients. Obes Surg. 2004; 14:635–637. Springer F, Machann J, Claussen CD, et al. Liver fat content determined by magnetic resonance imaging and spectroscopy. World J Gastroenterol. 2010;16:1560–1566. Rinella ME, Loomba R, Caldwell SH, et al. Controversies in the diagnosis and management of NAFLD and NASH. Gastroenterol Hepatol (N Y). 2014;10: 219–227. Reeder SB. Emerging quantitative magnetic resonance imaging biomarkers of hepatic steatosis. Hepatology. 2013;58: 1877–1880. Noureddin M, Lam J, Peterson MR, et al. Longitudinal comparison between MRI, MRS and histology-determined steatosis in NAFLD patients at two-time points in a randomized trial. Hepatology. 2013;58:1930–1940. Tang A, Tan J, Sun M, et al. Nonalcoholic fatty liver disease: MR imaging of liver proton density fat fraction to assess hepatic steatosis. Radiology. 2013;267:422–431. Reeder SB, Hu HH, Sirlin CB. Proton density fat-fraction: a standardized MRbased biomarker of tissue fat concentration. J Magn Reson Imaging. 2012; 36:1011–1014.
Evaluation of Metabolic Syndrome and Nonalcoholic Steatohepatitis To the Editor: We read with great interest the recently published article by Jung and colleagues in which the authors aimed to assess the relationship of metabolic syndrome (MetS)-associated nonalcoholic steatohepatitis (NASH) and insulin resistance (IR), and to define the correlation of chemicometabolic components with different degree of liver histology in NASH subjects. They concluded that patients with NASH showed increased IR with a significant association of MetS and the severity of hepatic fibrosis revealed a strong correlation with serum aspartate aminotransferase/alanine aminotransferase The authors declare that they have nothing to disclose.
Copyright
r
Volume 49, Number 4, April 2015
ratio and high-density lipoprotein cholesterol level.1 However, we think that there are some points that should be emphasized about this study. First, in the study by Jung and colleagues, excessive alcohol drinking is defined as average daily consumption of alcohol >20 g without any gender difference. However, according to guidelines, it is generally accepted as >30 g/d for men and >20 g/d for women.2 Therefore, improper use of this cutoff value could have led to patient selection bias in the original study. Second, there are several studies investigating serum/plasma and intracellular concentrations of water-soluble vitamins (vitamins B1, B3, B6, Cyetc.) and minerals (magnesium, seleniumyetc.) in MetS subjects.3–6 According to these studies, deficiencies of these vitamins and minerals were found to be associated with IR and increased risk for type-2 diabetes. These deficiencies may be secondary to decreased dietary intake or functional deficits resulting from coexisting diseases (conditions causing steatorrhea or severe chronic diarrhea such as Crohn’s disease, ulcerative colitis, celiac disease, short bowel syndromeyetc.). Moreover, an independent relationship between decreased serum magnesium levels and NASH was found in a study by Rodrı´ guez-Herna´ndez et al.7 Therefore, in such studies, evaluating NASH patients with coexisting MetS components, assessing plasma levels of certain vitamins and minerals involved in the development of NASH will provide more significant results and substantially improve the value of the article. Third, ordinal logistic regression analysis could be performed to determine the power of IR to predict the degree of fibrotic and inflammatory activity. In conclusion, using proper cutoff values would provide more reliable results. The assessment of certain vitamin and minerals, and performing ordinal logistic regression analysis for IR would improve the credibility of the whole article. Erdim Sertoglu, MD* Metin Uyanik, MDw Huseyin Kayadibi, MDz *Biochemistry Laboratory, Ankara Mevki Military Hospital, Anittepe Dispensary Ankara wBiochemistry Laboratory, Corlu Military Hospital, Tekirdag zBiochemistry Laboratory, Adana Military Hospital, Adana, Turkey
2014 Wolters Kluwer Health, Inc. All rights reserved.
J Clin Gastroenterol
Volume 49, Number 4, April 2015
REFERENCES 1. Jung KY, Cho SY, Kim HJ, et al. Nonalcoholic steatohepatitis associated with metabolic syndrome: relationship to insulin resistance and liver histology. J Clin Gastroenterol. 2014;48:883–888. 2. Chalasani N, Younossi Z, Lavine JE, et al. The diagnosis and management of non-alcoholic fatty liver disease: practice guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association. Hepatology. 2012;55:2005–2023. 3. Huerta MG, Roemmich JN, Kington ML, et al. Magnesium deficiency is associated with insulin resistance in obese children. Diabetes Care. 2005;28: 1175–1181. 4. Odum EP, Wakwe VC. Plasma concentrations of water-soluble vitamins in metabolic syndrome subjects. Niger J Clin Pract. 2012;15:442–447. 5. Brigelius-Flohe´ R. Introduction to serial reviews on selenium and diabetes type 2an unexpected link. Free Radic Biol Med. 2013;65:1536–1537. 6. Lima Mde L, Cruz T, Rodrigues LE, et al. Serum and intracellular magnesium deficiency in patients with metabolic syndrome—evidences for its relation to insulin resistance. Diabetes Res Clin Pract. 2009;83:257–262. 7. Rodrı´ guez-Herna´ndez H, Gonzalez JL, Rodrı´ guez-Mora´n M, et al. Hypomagnesemia, insulin resistance, and non-alcoholic steatohepatitis in obese subjects. Arch Med Res. 2005;36:362–366.
Carcinoid-associated Encephalopathy To the Editor: Here, we present an unusual case of acute encephalopathy which could have been potentially prevented by simple supplementation of tryptophan in a patient with large metastatic carcinoid tumor in the liver. An 80-year-old man presented to the Acute and Emergency Department with pyrexia (401C) and right upper abdominal pain radiating to back. Five days before he had undergone radiofrequency ablation (RFA) of an 8-cm liver lesion secondary to a P.E. has received funding from Medical Research Council, UK, Alzheimer’s Society, Alzheimer’s Drug Discovery foundation as research grants. He has also received funding from GE healthcare, Novo Nordisk, Piramal life science both for research and also received honoraria. The authors declare that they have nothing to disclose.
Copyright
r
neuroendocrine carcinoid; however, multiple smaller liver lesions were also present. On admission, he reported pain over the access site for RFA as the procedure and was associated with nausea and general malaise. However, there was an improvement in symptoms of diarrhea since RFA. Clinical examination demonstrated that the patient was hypotensive, tachycardic, and tachypnoic, with a normal abdominal examination. His initial blood results showed elevated C reactive protein levels, leucopoenia, and anemia. To rule out a post-RFA intrahepatic collection, an abdominal computed tomographic scan was performed showing normal post-RFA changes, and the patient was started on antibiotics, due to the initial impression of postprocedural sepsis. The blood cultures were positive for Escherichia coli and the patient was started on ertapenem and metronidazole. He improved after 5 days and was afebrile, with reduced C reactive protein levels. After 10 days, the patient started becoming confused and drowsy with clinical features of encephalopathy. However, there was no evidence of ongoing sepsis and blood cultures were negative, thus a brain magnetic resonance imaging (MRI) scan and an electroencephalogram (EEG) were performed. The EEG showed a diffuse mixture of y and d activities at 1.75 to 6.5 Hz with absent a-rhythm compatible with metabolic encephalopathy, whereas the MRI findings were essentially normal. Because of increased confusion and reduced Glasgow Coma Scale (Glasgow Coma Scale = 9/15), a lumbar puncture was performed, showing no signs of encephalitis. Initially, a diagnosis of paraneoplastic neurological syndrome was considered, which is described in patients with carcinoid. However, anti-Yo, antiHu, anti-Ri, anti-voltage gated K channel, antiglutamic acid decarboxylase, and anti-NMDA receptor antibodies were negative. Because of ongoing confusion and without any evidence of sepsis, a diagnosis of metabolic encephalopathy was made, based on clinical evidence of persistent encephalopathy, MRI findings (essentially normal), EEG features suggestive of metabolic encephalopathy and negative antineuronal antibodies. At this point, a diagnosis of encephalopathy secondary to low tryptophan was considered, and planned to replace tryptophan while waiting for laboratory results. Blood tryptophan level was low at 24 mmol\L suggesting possible encephalopathy secondary to tryptophan deficiency. After 10 days of oral
2014 Wolters Kluwer Health, Inc. All rights reserved.
Letters to the Editor
supplementation, levels reached normal range. The delay from the RFA to diagnosis of encephalopathy secondary to tryptophan was 7 weeks. Patients made initial improvement for few weeks, however, eventually succumbed to death in the hospital due to pneumonia. Even though paraneoplastic manifestations of malignant tumour and brain metastatic manifestations can occur in carcinoid patients,1,2 encephalopathy due to tryptophan deficiency is extremely rare, thus diagnosis of tryptophan deficiency encephalopathy could be easily missed. In carcinoid syndrome with large tumor, there is a 70-fold increase in the utilization of tryptophan, which can cause deficiency over a period of time. Due to the insidious onset of symptoms, the levels of tryptophan are not routinely measured even in metastatic carcinoid disease with large tumors. If these patients are suffering from concurrent infection, usually a diagnosis of delirium secondary to infection is made. However, in this case, patient demonstrated the features of metabolic encepahalopathy both clinically and in EEG without any evidence of derangement of usual metabolic parameters. This persistent metabolic encephalopathy prompted further investigation. Moreover, in our patient there was no evidence of metastatic tumor or paraneoplastic neurological syndrome. Previous case report has demonstrated that metabolic encephalopathy associated with carcinoid syndrome had responded to tryptophan replacement therapy.3 Following tryptophan administration, the patient’s cognitive state improved significantly. Our patient could have been tryptophan deficient for several weeks before the definite diagnosis of the deficiency was made and the deficiency could have begun immediately after the RFA or might have been precipitated by the RFA. The long-term effect of tryptophan on neuronal function, and whether these effects are reversible needs further investigation. To date, none of the studies on the long-term results of laparoscopic RFA for treating unresectable liver metastases from neuroendocrine tumors has reported tryptophan-related encephalopathy among the possible contributing factor or complication.4,5 Tryptophan is a branch chained amino acid that serves as the rate-limiting substrate for the production of serotonin6; acute tryptophan depletion in healthy volunteers specifically impairs long-term memory performance,7 whereas long-lasting tryptophan www.jcge.com |
353
Letters to the Editor
however, it has biases and is mainly used in research studies.5 Magnetic resonance imaging (MRI) has been proven to be accurate in detecting fat in the liver.6,7 MRI-determined proton density fat fraction (MRI-PDFF) is a novel technique that reduces the biases seen with MRS and has been shown to be highly correlated with MRS.8,9 It has been demonstrated that MRI-PDFF is accurate in quantifying liver fat.8,10 We recently showed that MRI-PDFF correlates highly with MRS in quantifying liver fat in patients enrolled in a clinical trial for nonalcoholic steatohepatitis.8 In contrast to MRS, MRI-PDFF is easier to apply, requires less time, is cheaper compared with MRS, and is now commercially available.7 Although underutilized, the fat fraction quantification is available on MR machines. Thus, we propose the use of MRI and, in particular, MRI-PDFF, as an alternative to CT scans and US in NAFLD diagnosis. This will allow for accurate quantification of liver fat and will be a useful tool for longitudinal follow-up. The cost of MRI is traditionally known to be higher than US. However, MRI-PDFF does not require contrast and can be performed in a short time. Indeed, Medicare data show an insignificant difference in price of this limited MRI in comparison with US.7 We do not believe that it is useful to expose patients to additional radiation by performing a CT scan when US imaging has already been shown to be uninformative and a more accurate means of diagnosing NAFLD is readily available. Mazen Noureddin, MD Cyrus Khoyilar, BS Suzanne L. Palmer, MD Department of Medicine, Division of Gastrointestinal and Liver Diseases (for Noureddin and Khoyilar), Department of Radiology (for Palmer) USC Keck School of Medicine Los Angeles, CA
REFERENCES 1. Review Team, LaBrecque DR, Abbas Z, Anania F, et al. World Gastroenterology Organisation global guidelines: nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. J Clin Gastroenterol. 2014;48:467–473. 2. Bohte AE, van Werven JR, Bipat S, et al. The diagnostic accuracy of US, CT, MRI and 1 H-MRS for the evaluation of hepatic steatosis compared with liver biopsy: a meta-analysis. Eur Radiol. 2011;21:87–97. 3. Limanond P, Raman SS, Lassman C, et al. Macrovesicular hepatic steatosis
352 | www.jcge.com
4.
5.
6.
7.
8.
9.
10.
in living related liver donors: correlation between CT and histologic findings. Radiology. 2004;230:276–280. Mottin CC, Moretto M, Padoin AV, et al. The role of ultrasound in the diagnosis of hepatic steatosis in morbidly obese patients. Obes Surg. 2004; 14:635–637. Springer F, Machann J, Claussen CD, et al. Liver fat content determined by magnetic resonance imaging and spectroscopy. World J Gastroenterol. 2010;16:1560–1566. Rinella ME, Loomba R, Caldwell SH, et al. Controversies in the diagnosis and management of NAFLD and NASH. Gastroenterol Hepatol (N Y). 2014;10: 219–227. Reeder SB. Emerging quantitative magnetic resonance imaging biomarkers of hepatic steatosis. Hepatology. 2013;58: 1877–1880. Noureddin M, Lam J, Peterson MR, et al. Longitudinal comparison between MRI, MRS and histology-determined steatosis in NAFLD patients at two-time points in a randomized trial. Hepatology. 2013;58:1930–1940. Tang A, Tan J, Sun M, et al. Nonalcoholic fatty liver disease: MR imaging of liver proton density fat fraction to assess hepatic steatosis. Radiology. 2013;267:422–431. Reeder SB, Hu HH, Sirlin CB. Proton density fat-fraction: a standardized MRbased biomarker of tissue fat concentration. J Magn Reson Imaging. 2012; 36:1011–1014.
Evaluation of Metabolic Syndrome and Nonalcoholic Steatohepatitis To the Editor: We read with great interest the recently published article by Jung and colleagues in which the authors aimed to assess the relationship of metabolic syndrome (MetS)-associated nonalcoholic steatohepatitis (NASH) and insulin resistance (IR), and to define the correlation of chemicometabolic components with different degree of liver histology in NASH subjects. They concluded that patients with NASH showed increased IR with a significant association of MetS and the severity of hepatic fibrosis revealed a strong correlation with serum aspartate aminotransferase/alanine aminotransferase The authors declare that they have nothing to disclose.
Copyright
r
Volume 49, Number 4, April 2015
ratio and high-density lipoprotein cholesterol level.1 However, we think that there are some points that should be emphasized about this study. First, in the study by Jung and colleagues, excessive alcohol drinking is defined as average daily consumption of alcohol >20 g without any gender difference. However, according to guidelines, it is generally accepted as >30 g/d for men and >20 g/d for women.2 Therefore, improper use of this cutoff value could have led to patient selection bias in the original study. Second, there are several studies investigating serum/plasma and intracellular concentrations of water-soluble vitamins (vitamins B1, B3, B6, Cyetc.) and minerals (magnesium, seleniumyetc.) in MetS subjects.3–6 According to these studies, deficiencies of these vitamins and minerals were found to be associated with IR and increased risk for type-2 diabetes. These deficiencies may be secondary to decreased dietary intake or functional deficits resulting from coexisting diseases (conditions causing steatorrhea or severe chronic diarrhea such as Crohn’s disease, ulcerative colitis, celiac disease, short bowel syndromeyetc.). Moreover, an independent relationship between decreased serum magnesium levels and NASH was found in a study by Rodrı´ guez-Herna´ndez et al.7 Therefore, in such studies, evaluating NASH patients with coexisting MetS components, assessing plasma levels of certain vitamins and minerals involved in the development of NASH will provide more significant results and substantially improve the value of the article. Third, ordinal logistic regression analysis could be performed to determine the power of IR to predict the degree of fibrotic and inflammatory activity. In conclusion, using proper cutoff values would provide more reliable results. The assessment of certain vitamin and minerals, and performing ordinal logistic regression analysis for IR would improve the credibility of the whole article. Erdim Sertoglu, MD* Metin Uyanik, MDw Huseyin Kayadibi, MDz *Biochemistry Laboratory, Ankara Mevki Military Hospital, Anittepe Dispensary Ankara wBiochemistry Laboratory, Corlu Military Hospital, Tekirdag zBiochemistry Laboratory, Adana Military Hospital, Adana, Turkey
2014 Wolters Kluwer Health, Inc. All rights reserved.
J Clin Gastroenterol
Volume 49, Number 4, April 2015
REFERENCES 1. Jung KY, Cho SY, Kim HJ, et al. Nonalcoholic steatohepatitis associated with metabolic syndrome: relationship to insulin resistance and liver histology. J Clin Gastroenterol. 2014;48:883–888. 2. Chalasani N, Younossi Z, Lavine JE, et al. The diagnosis and management of non-alcoholic fatty liver disease: practice guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association. Hepatology. 2012;55:2005–2023. 3. Huerta MG, Roemmich JN, Kington ML, et al. Magnesium deficiency is associated with insulin resistance in obese children. Diabetes Care. 2005;28: 1175–1181. 4. Odum EP, Wakwe VC. Plasma concentrations of water-soluble vitamins in metabolic syndrome subjects. Niger J Clin Pract. 2012;15:442–447. 5. Brigelius-Flohe´ R. Introduction to serial reviews on selenium and diabetes type 2an unexpected link. Free Radic Biol Med. 2013;65:1536–1537. 6. Lima Mde L, Cruz T, Rodrigues LE, et al. Serum and intracellular magnesium deficiency in patients with metabolic syndrome—evidences for its relation to insulin resistance. Diabetes Res Clin Pract. 2009;83:257–262. 7. Rodrı´ guez-Herna´ndez H, Gonzalez JL, Rodrı´ guez-Mora´n M, et al. Hypomagnesemia, insulin resistance, and non-alcoholic steatohepatitis in obese subjects. Arch Med Res. 2005;36:362–366.
Carcinoid-associated Encephalopathy To the Editor: Here, we present an unusual case of acute encephalopathy which could have been potentially prevented by simple supplementation of tryptophan in a patient with large metastatic carcinoid tumor in the liver. An 80-year-old man presented to the Acute and Emergency Department with pyrexia (401C) and right upper abdominal pain radiating to back. Five days before he had undergone radiofrequency ablation (RFA) of an 8-cm liver lesion secondary to a P.E. has received funding from Medical Research Council, UK, Alzheimer’s Society, Alzheimer’s Drug Discovery foundation as research grants. He has also received funding from GE healthcare, Novo Nordisk, Piramal life science both for research and also received honoraria. The authors declare that they have nothing to disclose.
Copyright
r
neuroendocrine carcinoid; however, multiple smaller liver lesions were also present. On admission, he reported pain over the access site for RFA as the procedure and was associated with nausea and general malaise. However, there was an improvement in symptoms of diarrhea since RFA. Clinical examination demonstrated that the patient was hypotensive, tachycardic, and tachypnoic, with a normal abdominal examination. His initial blood results showed elevated C reactive protein levels, leucopoenia, and anemia. To rule out a post-RFA intrahepatic collection, an abdominal computed tomographic scan was performed showing normal post-RFA changes, and the patient was started on antibiotics, due to the initial impression of postprocedural sepsis. The blood cultures were positive for Escherichia coli and the patient was started on ertapenem and metronidazole. He improved after 5 days and was afebrile, with reduced C reactive protein levels. After 10 days, the patient started becoming confused and drowsy with clinical features of encephalopathy. However, there was no evidence of ongoing sepsis and blood cultures were negative, thus a brain magnetic resonance imaging (MRI) scan and an electroencephalogram (EEG) were performed. The EEG showed a diffuse mixture of y and d activities at 1.75 to 6.5 Hz with absent a-rhythm compatible with metabolic encephalopathy, whereas the MRI findings were essentially normal. Because of increased confusion and reduced Glasgow Coma Scale (Glasgow Coma Scale = 9/15), a lumbar puncture was performed, showing no signs of encephalitis. Initially, a diagnosis of paraneoplastic neurological syndrome was considered, which is described in patients with carcinoid. However, anti-Yo, antiHu, anti-Ri, anti-voltage gated K channel, antiglutamic acid decarboxylase, and anti-NMDA receptor antibodies were negative. Because of ongoing confusion and without any evidence of sepsis, a diagnosis of metabolic encephalopathy was made, based on clinical evidence of persistent encephalopathy, MRI findings (essentially normal), EEG features suggestive of metabolic encephalopathy and negative antineuronal antibodies. At this point, a diagnosis of encephalopathy secondary to low tryptophan was considered, and planned to replace tryptophan while waiting for laboratory results. Blood tryptophan level was low at 24 mmol\L suggesting possible encephalopathy secondary to tryptophan deficiency. After 10 days of oral
2014 Wolters Kluwer Health, Inc. All rights reserved.
Letters to the Editor
supplementation, levels reached normal range. The delay from the RFA to diagnosis of encephalopathy secondary to tryptophan was 7 weeks. Patients made initial improvement for few weeks, however, eventually succumbed to death in the hospital due to pneumonia. Even though paraneoplastic manifestations of malignant tumour and brain metastatic manifestations can occur in carcinoid patients,1,2 encephalopathy due to tryptophan deficiency is extremely rare, thus diagnosis of tryptophan deficiency encephalopathy could be easily missed. In carcinoid syndrome with large tumor, there is a 70-fold increase in the utilization of tryptophan, which can cause deficiency over a period of time. Due to the insidious onset of symptoms, the levels of tryptophan are not routinely measured even in metastatic carcinoid disease with large tumors. If these patients are suffering from concurrent infection, usually a diagnosis of delirium secondary to infection is made. However, in this case, patient demonstrated the features of metabolic encepahalopathy both clinically and in EEG without any evidence of derangement of usual metabolic parameters. This persistent metabolic encephalopathy prompted further investigation. Moreover, in our patient there was no evidence of metastatic tumor or paraneoplastic neurological syndrome. Previous case report has demonstrated that metabolic encephalopathy associated with carcinoid syndrome had responded to tryptophan replacement therapy.3 Following tryptophan administration, the patient’s cognitive state improved significantly. Our patient could have been tryptophan deficient for several weeks before the definite diagnosis of the deficiency was made and the deficiency could have begun immediately after the RFA or might have been precipitated by the RFA. The long-term effect of tryptophan on neuronal function, and whether these effects are reversible needs further investigation. To date, none of the studies on the long-term results of laparoscopic RFA for treating unresectable liver metastases from neuroendocrine tumors has reported tryptophan-related encephalopathy among the possible contributing factor or complication.4,5 Tryptophan is a branch chained amino acid that serves as the rate-limiting substrate for the production of serotonin6; acute tryptophan depletion in healthy volunteers specifically impairs long-term memory performance,7 whereas long-lasting tryptophan www.jcge.com |
353
