- Email: [email protected]
Chest pain and the oesophagus
119
tissues. In the
remaining
7 cases, tissues
were not
available for
testing. All cases lacking a definite diagnosis were analysed in detail. In 26 patient was classified as lost to follow-up by the responsible clinician. Of these, 5 women had returned to their country of origin for delivery, 2 failed to keep appointments, and 3 were subject to administrative errors. 1 mother had refused further medical care and 1 child had been discharged, erroneously, on the basis of a normal clinical appearance. Details of the other 14 cases were not stated. The clinicians responsible for the other 36 cases without a definite diagnosis but with continued medical contact were sent further literature describing the recommended investigation of toxoplasmosis in pregnancy and asked to provide information about outcome of the patient. 25 recipients did not reply; 5 children were subsequently shown to be free of infection; 3 cases failed to keep further appointments; and in 2 cases the clinician decided further investigation of the child would result in unacceptable parental anxiety.1 child was mistakenly discharged after the parasite had not cases the
been isolated at cordocentesis before delivery. Our intervention resulted in 61 of 130 cases (47%) achieving a substantiated final diagnosis compared with 30% of cases before instigation of the programmed The resolution of additional cases involved an average of 2-7 h administrative work per patient. These findings illustrate the influence of patient’s and physician’s compliance on the optimal investigation of toxoplasmosis in pregnancy. These limitations should be included in any cost-benefit analysis of antenatal screening for toxoplasmosis. This work was
supported by
a
grant from Birthright.
Toxoplasma Reference Laboratory, Public Health Laboratory Service, St George’s Hospital, London SW170QT, UK 1. Hartup C, Johnson JD, Holliman RE. 317-18.
C. HARTUP J. D. JOHNSON R. E. HOLLIMAN Toxoplasma and pregnancy. Lancet 1991; 338:
Aflatoxin biomarkers SIR,-Dr Hall and C. P. Wild (June 6, p 1413) in their comments about our report (April 18, p 943) provide a thoughtful assessment of several important issues related to the interaction between chronic hepatitis B virus infection and urinary biomarkers of aflatoxin exposure and liver cancer risk. We, too, were initially surprised at the strength of this relation and have considered several points they raise. As Hall and Wild suggest, it is feasible that aflatoxin exposure is fairly constant among individuals in Shanghai over time, but only repeated sampling in the same individuals can fully assess this possibility. After additional analysis of our data, we have found further evidence that aflatoxin-guanine adduct concentrations in urine, and not those of the parent compound or other metabolites, are the critical biomarker of risk. This not only lends further biological credibility to our findings but also supports the idea that individual metabolism of aflatoxins might be as critical, if not more so, than exposure itself in determining risk. We have also considered the possibility that aflatoxin-guanine adducts in urine might be a better measure of long-term exposure than other urinary biomarkers. Still, one is left with the strong possibility that misclassification may have occurred and that the true association and interaction might be substantially larger than observed. We chose to report our findings after a short follow-up because of the widespread interest in this topic. To assess the possibility of the tumour affecting diet and/or hepatic metabolism, we examined the aflatoxin and liver cancer association among cases diagnosed within 24 months offollow-up separately from those diagnosed after longer follow-up. Stronger associations between aflatoxin biomarkers and liver cancer risk were actually seen for the longer than for the shorter follow-up interval (for the parent compound, aflatoxin B1 for example, 6 of 7 cases identified after 24 months of follow-up vs 15 of 35 controls were positive, yielding a relative risk of 7-4). Moreover, as we note in our paper, associations were observed for three separate metabolic endpoints of aflatoxin Bp suggesting a strong relation between urinary markers and liver cancer risk that is independent of latent disease effects.
A self-reported history of cirrhosis of the liver was a strong risk factor for liver cancer in our study (3 of 22 cases vs 2 of 140 controls, relative risk 75), as was a history of any chronic liver disease (8 of 22 cases vs 19 of 140 controls, relative risk 3-3). The association with aflatoxin biomarkers was similarly strong when we excluded all subjects with a history of self-reported chronic liver disease from the
analysis. We agree strongly with Hall and Wild about the importance of understanding the precise nature of the interaction between
hepatitis B virus infection and aflatoxin exposure in hepatocellular carcinogenesis, especially the relative timing of these two exposures. In Chongming Island, a high-risk region for liver cancer near Shanghai, there has been a substantial reduction in consumption of maize, the principal source of dietary aflatoxins, since the 1960s. A subsequent gradual reduction in liver cancer mortality seems to have occurred.2 Although very indirect, these observations support the possibility that liver cancer rates might be reduced reasonably quickly by systematic removal of major sources of aflatoxin from the diet. Kenneth Norns Jr Comprehensive Cancer Center, University of Southern California School of Medicine, Los Angeles, 90033 California, USA
RONALD K. Ross MIMI C. YU BRIAN E. HENDERSON
JIAN-MIN YUAN GENG-SUN QIAN
JI-TAO Tu
Shanghai Cancer Institute, Shanghai, People’s Republic of China
YU-TANG GAO
Division of Toxicology, Massachusetts Institute of Technology, Boston
Division of Environmental Chemistry and Johns Hopkins University, Baltimore
GERALD N. WOGAN Biology,
JOHN D. GROOPMAN
Qian G-S, Yu MC, Ross RK, et al. Aflatoxin exposure and hepatocellular carcinoma in Shanghai, People’s Republic of China. Cancer Epidemiol Biomarkers Prev (in press). 2. Tu J-T, Gao R-N, Zhang D-H, Gu B-C. Hepatitis B virus and primary liver cancer on Chongming Island, People’s Republic of China. Natl Cancer Inst Monograph 1985; 1.
69: 213-15.
Chest
pain and the oesophagus
SIR,-In response to your March 7 editorial (p 583), Professor Cheng writes (April 25, p 1049) that mitral valve prolapse (MVP) with its associated cryptic chest pain should be considered in such patients. As Cheng notes, oesophageal dysmotility has been amply demonstrated in patients with MVP. However, I do not believe that this should be regarded as an isolated gut disorder in these patients. In 1985 I reported an increased frequency of irritable bowel syndrome (IBS) in patients with MVP.1 I suggested that the disordered oesophageal motility that is seen in such patients1 might also account for the cryptic chest pain of MVP. Both MVP and IBS symptoms arise more frequently in women. Because neurohorinonal3 ’ and associated psychiatric abnonnalitiess,6 have been described in both disorders, perhaps there is a common pathogenesis for the two entities. In addition to oesophageal dysmotility, patients with MVP commonly have other gut complaints that should not be overlooked. As a practising community gastroenterologist I believe that IBS would best explain the gut symptoms of patients with MVP. 366 South Main Steet, Connecticut 06410, USA 1. Sataline L. Irritable bowel
LEE SATALINE
syndrome and mitral valve prolapse syndrome. JAMA 1985; 253: 41. 2 Whorwell FJ, Clouter C, Smith CL. Oesophageal motility in irritable bowel syndrome. BMJ 1981; 282: 1101-02. 3. Kellow JE, Phillips SF. Altered small bowel motility in irritable bowel syndrome is correlated with symptoms. Gastroenterology 1987; 92: 1885-93. 4. Abrahamsson H. Gastrointestinal motility in patients with the irritable bowel syndrome. Scand J Gastroenterol 1987; 130 (suppl): 21-26. 5. Devereux RB, Kramer-Fox R, Kligfield P. Mitral valve prolapse: causes, clinical manifestations and management. Ann Intern Med 1989; 111: 305-17. 6. Drossman DA, McKee DC, Sandler RS, et al. Psychological factors in the irritable bowel syndrome: a multivariate study of patients and non-patients with irritable bowel syndrome. Gastroenterology 1988; 95: 701-08.
tissues. In the
remaining
7 cases, tissues
were not
available for
testing. All cases lacking a definite diagnosis were analysed in detail. In 26 patient was classified as lost to follow-up by the responsible clinician. Of these, 5 women had returned to their country of origin for delivery, 2 failed to keep appointments, and 3 were subject to administrative errors. 1 mother had refused further medical care and 1 child had been discharged, erroneously, on the basis of a normal clinical appearance. Details of the other 14 cases were not stated. The clinicians responsible for the other 36 cases without a definite diagnosis but with continued medical contact were sent further literature describing the recommended investigation of toxoplasmosis in pregnancy and asked to provide information about outcome of the patient. 25 recipients did not reply; 5 children were subsequently shown to be free of infection; 3 cases failed to keep further appointments; and in 2 cases the clinician decided further investigation of the child would result in unacceptable parental anxiety.1 child was mistakenly discharged after the parasite had not cases the
been isolated at cordocentesis before delivery. Our intervention resulted in 61 of 130 cases (47%) achieving a substantiated final diagnosis compared with 30% of cases before instigation of the programmed The resolution of additional cases involved an average of 2-7 h administrative work per patient. These findings illustrate the influence of patient’s and physician’s compliance on the optimal investigation of toxoplasmosis in pregnancy. These limitations should be included in any cost-benefit analysis of antenatal screening for toxoplasmosis. This work was
supported by
a
grant from Birthright.
Toxoplasma Reference Laboratory, Public Health Laboratory Service, St George’s Hospital, London SW170QT, UK 1. Hartup C, Johnson JD, Holliman RE. 317-18.
C. HARTUP J. D. JOHNSON R. E. HOLLIMAN Toxoplasma and pregnancy. Lancet 1991; 338:
Aflatoxin biomarkers SIR,-Dr Hall and C. P. Wild (June 6, p 1413) in their comments about our report (April 18, p 943) provide a thoughtful assessment of several important issues related to the interaction between chronic hepatitis B virus infection and urinary biomarkers of aflatoxin exposure and liver cancer risk. We, too, were initially surprised at the strength of this relation and have considered several points they raise. As Hall and Wild suggest, it is feasible that aflatoxin exposure is fairly constant among individuals in Shanghai over time, but only repeated sampling in the same individuals can fully assess this possibility. After additional analysis of our data, we have found further evidence that aflatoxin-guanine adduct concentrations in urine, and not those of the parent compound or other metabolites, are the critical biomarker of risk. This not only lends further biological credibility to our findings but also supports the idea that individual metabolism of aflatoxins might be as critical, if not more so, than exposure itself in determining risk. We have also considered the possibility that aflatoxin-guanine adducts in urine might be a better measure of long-term exposure than other urinary biomarkers. Still, one is left with the strong possibility that misclassification may have occurred and that the true association and interaction might be substantially larger than observed. We chose to report our findings after a short follow-up because of the widespread interest in this topic. To assess the possibility of the tumour affecting diet and/or hepatic metabolism, we examined the aflatoxin and liver cancer association among cases diagnosed within 24 months offollow-up separately from those diagnosed after longer follow-up. Stronger associations between aflatoxin biomarkers and liver cancer risk were actually seen for the longer than for the shorter follow-up interval (for the parent compound, aflatoxin B1 for example, 6 of 7 cases identified after 24 months of follow-up vs 15 of 35 controls were positive, yielding a relative risk of 7-4). Moreover, as we note in our paper, associations were observed for three separate metabolic endpoints of aflatoxin Bp suggesting a strong relation between urinary markers and liver cancer risk that is independent of latent disease effects.
A self-reported history of cirrhosis of the liver was a strong risk factor for liver cancer in our study (3 of 22 cases vs 2 of 140 controls, relative risk 75), as was a history of any chronic liver disease (8 of 22 cases vs 19 of 140 controls, relative risk 3-3). The association with aflatoxin biomarkers was similarly strong when we excluded all subjects with a history of self-reported chronic liver disease from the
analysis. We agree strongly with Hall and Wild about the importance of understanding the precise nature of the interaction between
hepatitis B virus infection and aflatoxin exposure in hepatocellular carcinogenesis, especially the relative timing of these two exposures. In Chongming Island, a high-risk region for liver cancer near Shanghai, there has been a substantial reduction in consumption of maize, the principal source of dietary aflatoxins, since the 1960s. A subsequent gradual reduction in liver cancer mortality seems to have occurred.2 Although very indirect, these observations support the possibility that liver cancer rates might be reduced reasonably quickly by systematic removal of major sources of aflatoxin from the diet. Kenneth Norns Jr Comprehensive Cancer Center, University of Southern California School of Medicine, Los Angeles, 90033 California, USA
RONALD K. Ross MIMI C. YU BRIAN E. HENDERSON
JIAN-MIN YUAN GENG-SUN QIAN
JI-TAO Tu
Shanghai Cancer Institute, Shanghai, People’s Republic of China
YU-TANG GAO
Division of Toxicology, Massachusetts Institute of Technology, Boston
Division of Environmental Chemistry and Johns Hopkins University, Baltimore
GERALD N. WOGAN Biology,
JOHN D. GROOPMAN
Qian G-S, Yu MC, Ross RK, et al. Aflatoxin exposure and hepatocellular carcinoma in Shanghai, People’s Republic of China. Cancer Epidemiol Biomarkers Prev (in press). 2. Tu J-T, Gao R-N, Zhang D-H, Gu B-C. Hepatitis B virus and primary liver cancer on Chongming Island, People’s Republic of China. Natl Cancer Inst Monograph 1985; 1.
69: 213-15.
Chest
pain and the oesophagus
SIR,-In response to your March 7 editorial (p 583), Professor Cheng writes (April 25, p 1049) that mitral valve prolapse (MVP) with its associated cryptic chest pain should be considered in such patients. As Cheng notes, oesophageal dysmotility has been amply demonstrated in patients with MVP. However, I do not believe that this should be regarded as an isolated gut disorder in these patients. In 1985 I reported an increased frequency of irritable bowel syndrome (IBS) in patients with MVP.1 I suggested that the disordered oesophageal motility that is seen in such patients1 might also account for the cryptic chest pain of MVP. Both MVP and IBS symptoms arise more frequently in women. Because neurohorinonal3 ’ and associated psychiatric abnonnalitiess,6 have been described in both disorders, perhaps there is a common pathogenesis for the two entities. In addition to oesophageal dysmotility, patients with MVP commonly have other gut complaints that should not be overlooked. As a practising community gastroenterologist I believe that IBS would best explain the gut symptoms of patients with MVP. 366 South Main Steet, Connecticut 06410, USA 1. Sataline L. Irritable bowel
LEE SATALINE
syndrome and mitral valve prolapse syndrome. JAMA 1985; 253: 41. 2 Whorwell FJ, Clouter C, Smith CL. Oesophageal motility in irritable bowel syndrome. BMJ 1981; 282: 1101-02. 3. Kellow JE, Phillips SF. Altered small bowel motility in irritable bowel syndrome is correlated with symptoms. Gastroenterology 1987; 92: 1885-93. 4. Abrahamsson H. Gastrointestinal motility in patients with the irritable bowel syndrome. Scand J Gastroenterol 1987; 130 (suppl): 21-26. 5. Devereux RB, Kramer-Fox R, Kligfield P. Mitral valve prolapse: causes, clinical manifestations and management. Ann Intern Med 1989; 111: 305-17. 6. Drossman DA, McKee DC, Sandler RS, et al. Psychological factors in the irritable bowel syndrome: a multivariate study of patients and non-patients with irritable bowel syndrome. Gastroenterology 1988; 95: 701-08.