Letters to the Editor To the Editor:
We read with great interest the paper by Teitelbaum et al [I] concerning the monitoring of intestinal transplant rejection in rats by use of serial measurements of small bowel maltase, sucrase, and lactase activity. These authors found good correlation between the decline in intestinal disaccharidase activity and the occurrence of transplanted bowel rejeu tion. We evaluated the utility of serum maltase as a diagnostic and prognostic indicator in a rat model of partial, complete, and strangulated intestinal obstruction [2]. Our findings are similar to those of Teitelbaum et al: declining activities of maltase portend a poor prognosis, whereas increasing activities appear to be associated with regeneration of bowel mucosa and a favorable prognosis. A comparison of our work with that of these authors shows that the sequence of changes in serum maltase activity over time closely approximates the changes observed in bowel mucosa, suggesting a direct relationship between serum and bowel maltase activity. We believe that the analysis of serum maltase activity is the simplest and the least invasive diagnostic procedure permitting rapid and inexpensive serial determinations. Although measurement of disao charidase activities in bowel mucosa and serum appears to be useful for monitoring mucosal injury in rats, the applicability of these tests in human subjects is unknown. Disaccharidase measurements in humans are limited to bowel mucosa specimens, because the disaccharidases are usually unmeasurable in human plasma. The measurement of disaccharidase activities in human mucosa specimens, however, is hampered by the wide variations in activity between patients, making interpretation difticult [3]. Also, because the mucosal disaccharidase activity must be expressed in units of enzyme activity per wet tissue weight or units of enzyme activity per gram of protein present, any imprecision associated with measurement of tissue weights or protein concentrations will affect the accuracy of this test. Finally, the 90
extreme difference in disaccharidase activities between duodenum and jejunum further complicates the interpretation of results [4]. The advantages of an easily measured serum marker of mucosal integrity are obvious. One such candidate appears to be diamine oxidase. The localization of diamine oxidase in the cytosolic fraction of the enterocytes probably accounts for its presence in the blood. By contrast, the disaccharidases are found in the brush border cells and are eventually lost into the intestinal lumen when the cells are shed. Previous studies have demonstrated a significant positive correlation between disaccharidase and diamine oxidase activities in the intestinal mucosa [3,4]. Tissue diamine oxidase also shows less variation in activity in comparison to the disaccharidases [3]. The activity of serum diamine oxidase may be a more accurate reflection of functional mucosa than the measurement of mucosal disaccharidase activities. Previous studies in animals have shown diamine oxidase activity in serum to quantitate accurately the length of intestinal mucosal injury [5]. Measurement of diamine oxidase activity in serum may become an extremely useful diagnostic and prognostic indicator of injury to the intestinal mucosa. The analysis of disaccharidase activities in intestinal biopsy specimens should be interpreted with caution, because of the many variables that significantly affect the final results. Steven C. Kazmierczak, MD East Carolina University School of Medicine Greenville, NC John A. Lot& MD The Ohio State University Columbus, OH 1. Teitelbaum DH, Wise WE, Sonnino RE,
et al. Monitoring of intestinal transplant rejection. Am J Surg 1989; 157: 318-22. 2. Kazmierczak SC, Lott JA. Acute intestinal infarction or obstruction: search for better laboratory tests in an animal model. Clin Chem 1988; 34: 281-8. 3. Forget P, Grandfils C, Van Cutsem JL, Dandrifosse G. Diamine oxidase and disaccharidase activities in small intestinal biopsies of children. Ped Res 1984; 18: 647-9. 4. Bergoz R, Griessen M, Infante F, De Peyer R, Vallotton MC. Significance of duo-
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denal disaccharidases. Digestion 198 1; 22: 108. 5. Luk GD, Bayliss TM, Baylin SB. Diamine oxidase: a circulating marker for rat intestinal mucosal maturation and integrity. J Clin Invest 1980; 66: 66-70.
To the Editor:
We read with interest the lead article in the November 1989 issue [I 1. In our opinion, the study is flawed by numerous shortcomings: the small number of patients, the paucity of data regarding postoperative complications, the failure to discern whether the operative subgroups were comparable, and the inexactness of combining all tumor recurrences, whether they were located in the bed of the resected thyroid, within residual thyroid tissue, spread to lymph nodes, or distant metastases. In contrast to the initial premise that “the advantages of total thyroidectomy have been well documented,” we submit that their selection of the available material was biased. Total thyroidectomy has not been proven superior to near-total thyroidectomy for differentiated thyroid carcinoma with respect to cause-specific mortality, local recurrence, or distant metastases. In fact, we believe convincing data have been published that are in direct contradiction [2-41. Additionally, the fact that 6 of the authors’ 20 patients (30%) who underwent “total thyroidectomy” required I- 131 ablation implies significant residual uptake in the neck, and no scan data are provided on the remaining 14 patients. To use phrases such as “some other procedure” and “lesser procedure” seems inexact and fails to give specific information regarding the types of operations performed other than the attempted total thyroidectomies. With reference to the editorial comment [5], we would agree that reports which detail very good results involving techniques that cannot be matched by the “real world of surgical practice” are potentially detrimental. Total thyroidectomy may well be effectively and safely employed by a large segment of “non-thyroid surgeon experts.” However, in our opin-
ion, the study by Arnold and Edge does not provide meaningful support for the contention that total thyroidectomy is more efficacious or as safe as a near-total thyroidectomy in which a small amount of thyroid tissue is left to protect parathyroid blood supply or the recurrent laryngeal nerves. Clive S. Grant, MD Jon A. van Heerden, MB Ian D. Hay, FRCP Department of Surgery Mayo Clinic Rochester, MN 1. Arnold RE, Edge BK. A descriptive experience of total thyroidectomy as the initial operation for differentiated carcinoma of the thyroid. Am J Surg 1989; 158: 396-8. 2. Hay ID, Grant CS, Taylor WF, McConahey WM. Ipsilateral lobectomy versus bilateral lobar resection in papillary thyroid carcinoma: a retrospective analysis of surgical outcome using a novel prognostic scoring system. Surgery 1987; 102: 1088-95. 3. Grant CS, Hay ID, Cough IR, Bergstralh EJ, Goellner JR, McConahey WM. Local recurrence in papillary thyroid carcinoma: is extent of surgical resection important? Surgery 1988; 104: 954-62. 4. Cady B, Rossi R. An expanded view of risk-group definition in differentiated thyroid carcinoma. Surgery 1988; 104: 947-53.
In Reaponse:
The following are my responses to the questions raised by Drs. Grant, van Heerden, and Hay: 1. The number of patients may have been small, but it was all we had. All of the patients were included so there could not have been any bias. 2. There were no distant metastases and all patients were operated on for cure. The high-risk group consisted of patients who had one or more of the criteria considered adverse, i.e., age, tumor size, metastasis, local invasion, and previous irradiation. All other patients were considered low risk. Although a numerical value was not assigned to each factor and some patients had more than one adverse factor, the results indicate that the subgroups were truly high risk and low risk. 3. Regarding the inexactness of combining all tumor recurrences, I concede that the prognoses for these recurrences differ but my premise is
that all recurrences are undesirable, require treatment, and represent a failure of the original surgery to control the disease. The operation which results in the fewest recurrences or deaths is the best operation. 4. To support their contention that “6 of the authors’ 20 patients (30%) who underwent ‘total thyroidectomy’ required I- 131 ablation implies significant residual uptake in the neck, and no scan data are provided on the remaining 14 patients,” they have cited three articles, two of which were written by their own unit. One of these [I] represents 860 patients treated from 1946 to 1970 and states “only 3% of patients underwent postoperative radioiodine ablation.” The other paper [2] represents 1,039 patients treated from 1946 to 1975 and states “postoperative 113’ scans were rarely obtained during this period.” Neither article provided scan data on these or their remaining patients. I do not believe that six ab lations in this group is unusual or detracts from the premise that total thyroidectomy is a better procedure. 5. The operative reports were studied and the lesser procedures consisted of subtotal, near-total, or lobectomy plus contralateral thyroid tissue. As the thyroid gland has no anatomic subdivisions, one can only estimate the amount of tissue the op erating surgeon left behind. Exactness is impossible. In both of the references cited [1,2], which were written by them, near-total and subtotal thyroidectomies were placed in the same group for statistical purposes. 6. They state that “convincing data have been published which is in direct contradiction” [1-31 to the conclusion that total thyroidectomy is superior to near-total thyroidectomy with respect to cause-specific mortality, local recurrence, or distant metastases. The first article cited [I] was a comparison of total thyroidectomy versus bilateral subtotal or neartotal thyroidectomy for high-risk tumors. Although there was a lower percentage of survivors in the total thyroidectomy group, the article stated that the AGES score for the total thyroidectomy group was sig-
nificantly higher and therefore this group had more aggressive disease. The second reference cited [2] was a comparison of recurrence rates in high- and low-risk patients. In the low-risk group, less than 2% of 131 total thyroidectomy patients had recurrences after 30 years, while over 5% of 610 bilateral subtotal or neartotal thyroidectomy patients had recurrences. Of the high-risk group, 52 patients had a near-total or subtotal thyroidectomy with a recurrence rate slightly over 20% after 30 years. There were 25 total thyroidectomy patients in the high-risk group with a recurrence rate slightly over 10% after 30 years. The total reference cited [3] did not present any data comparing total thyroidectomy patients with subtotal or near-total patients. I do not believe the data in these references merit the conclusion that “convincing data have been published that are in direct contradiction” to the statement that the advantages of total thyroidectomy have been well documented. 7. Other than one patient who was discussed in the original article, there were no postoperative complications. This “paucity of data” was the reason for writing the article. Grant et al [2] have stated that “resistance to routinely performing total thyroidectomy stems principally from its risks.” I disagree with their statement. I believe the conclusion that the average properly trained surgeon possesses the necessary skill to perform a total thyroidectomy without significant complications is valid. Capt. Robert E. Arnold, MD, FACS Naval Amphibious Base Little Creek, VA 1. Hay ID, Grant CS, Taylor WF, McConahey WM. Ipsilateral lobectomy versus bilateral lobar resection in papillary thyroid carcinoma: a retrospective analysis of surgical outcome using a novel prognostic scoring system. Surgery 1987; 102: 1088-95. 2. Grant CS, Hay ID, Cough IR, Bergstralh EJ, Goellner JR, McConahey WM. Local recurrence in papillary thyroid carcinoma: is extent of surgical resection important? Surgery 1988; 104: 954-62. 3. Cady B, Rossi R. An expanded view of risk-group definition in differentiated thyroid carcinoma. Surgery 1988; 104: 947-53.
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We read with great interest the paper by Teitelbaum et al [I] concerning the monitoring of intestinal transplant rejection in rats by use of serial measurements of small bowel maltase, sucrase, and lactase activity. These authors found good correlation between the decline in intestinal disaccharidase activity and the occurrence of transplanted bowel rejeu tion. We evaluated the utility of serum maltase as a diagnostic and prognostic indicator in a rat model of partial, complete, and strangulated intestinal obstruction [2]. Our findings are similar to those of Teitelbaum et al: declining activities of maltase portend a poor prognosis, whereas increasing activities appear to be associated with regeneration of bowel mucosa and a favorable prognosis. A comparison of our work with that of these authors shows that the sequence of changes in serum maltase activity over time closely approximates the changes observed in bowel mucosa, suggesting a direct relationship between serum and bowel maltase activity. We believe that the analysis of serum maltase activity is the simplest and the least invasive diagnostic procedure permitting rapid and inexpensive serial determinations. Although measurement of disao charidase activities in bowel mucosa and serum appears to be useful for monitoring mucosal injury in rats, the applicability of these tests in human subjects is unknown. Disaccharidase measurements in humans are limited to bowel mucosa specimens, because the disaccharidases are usually unmeasurable in human plasma. The measurement of disaccharidase activities in human mucosa specimens, however, is hampered by the wide variations in activity between patients, making interpretation difticult [3]. Also, because the mucosal disaccharidase activity must be expressed in units of enzyme activity per wet tissue weight or units of enzyme activity per gram of protein present, any imprecision associated with measurement of tissue weights or protein concentrations will affect the accuracy of this test. Finally, the 90
extreme difference in disaccharidase activities between duodenum and jejunum further complicates the interpretation of results [4]. The advantages of an easily measured serum marker of mucosal integrity are obvious. One such candidate appears to be diamine oxidase. The localization of diamine oxidase in the cytosolic fraction of the enterocytes probably accounts for its presence in the blood. By contrast, the disaccharidases are found in the brush border cells and are eventually lost into the intestinal lumen when the cells are shed. Previous studies have demonstrated a significant positive correlation between disaccharidase and diamine oxidase activities in the intestinal mucosa [3,4]. Tissue diamine oxidase also shows less variation in activity in comparison to the disaccharidases [3]. The activity of serum diamine oxidase may be a more accurate reflection of functional mucosa than the measurement of mucosal disaccharidase activities. Previous studies in animals have shown diamine oxidase activity in serum to quantitate accurately the length of intestinal mucosal injury [5]. Measurement of diamine oxidase activity in serum may become an extremely useful diagnostic and prognostic indicator of injury to the intestinal mucosa. The analysis of disaccharidase activities in intestinal biopsy specimens should be interpreted with caution, because of the many variables that significantly affect the final results. Steven C. Kazmierczak, MD East Carolina University School of Medicine Greenville, NC John A. Lot& MD The Ohio State University Columbus, OH 1. Teitelbaum DH, Wise WE, Sonnino RE,
et al. Monitoring of intestinal transplant rejection. Am J Surg 1989; 157: 318-22. 2. Kazmierczak SC, Lott JA. Acute intestinal infarction or obstruction: search for better laboratory tests in an animal model. Clin Chem 1988; 34: 281-8. 3. Forget P, Grandfils C, Van Cutsem JL, Dandrifosse G. Diamine oxidase and disaccharidase activities in small intestinal biopsies of children. Ped Res 1984; 18: 647-9. 4. Bergoz R, Griessen M, Infante F, De Peyer R, Vallotton MC. Significance of duo-
THE AMERICAN JOURNAL OF SURGERY
VOLUME 162 JULY 199 1
denal disaccharidases. Digestion 198 1; 22: 108. 5. Luk GD, Bayliss TM, Baylin SB. Diamine oxidase: a circulating marker for rat intestinal mucosal maturation and integrity. J Clin Invest 1980; 66: 66-70.
To the Editor:
We read with interest the lead article in the November 1989 issue [I 1. In our opinion, the study is flawed by numerous shortcomings: the small number of patients, the paucity of data regarding postoperative complications, the failure to discern whether the operative subgroups were comparable, and the inexactness of combining all tumor recurrences, whether they were located in the bed of the resected thyroid, within residual thyroid tissue, spread to lymph nodes, or distant metastases. In contrast to the initial premise that “the advantages of total thyroidectomy have been well documented,” we submit that their selection of the available material was biased. Total thyroidectomy has not been proven superior to near-total thyroidectomy for differentiated thyroid carcinoma with respect to cause-specific mortality, local recurrence, or distant metastases. In fact, we believe convincing data have been published that are in direct contradiction [2-41. Additionally, the fact that 6 of the authors’ 20 patients (30%) who underwent “total thyroidectomy” required I- 131 ablation implies significant residual uptake in the neck, and no scan data are provided on the remaining 14 patients. To use phrases such as “some other procedure” and “lesser procedure” seems inexact and fails to give specific information regarding the types of operations performed other than the attempted total thyroidectomies. With reference to the editorial comment [5], we would agree that reports which detail very good results involving techniques that cannot be matched by the “real world of surgical practice” are potentially detrimental. Total thyroidectomy may well be effectively and safely employed by a large segment of “non-thyroid surgeon experts.” However, in our opin-
ion, the study by Arnold and Edge does not provide meaningful support for the contention that total thyroidectomy is more efficacious or as safe as a near-total thyroidectomy in which a small amount of thyroid tissue is left to protect parathyroid blood supply or the recurrent laryngeal nerves. Clive S. Grant, MD Jon A. van Heerden, MB Ian D. Hay, FRCP Department of Surgery Mayo Clinic Rochester, MN 1. Arnold RE, Edge BK. A descriptive experience of total thyroidectomy as the initial operation for differentiated carcinoma of the thyroid. Am J Surg 1989; 158: 396-8. 2. Hay ID, Grant CS, Taylor WF, McConahey WM. Ipsilateral lobectomy versus bilateral lobar resection in papillary thyroid carcinoma: a retrospective analysis of surgical outcome using a novel prognostic scoring system. Surgery 1987; 102: 1088-95. 3. Grant CS, Hay ID, Cough IR, Bergstralh EJ, Goellner JR, McConahey WM. Local recurrence in papillary thyroid carcinoma: is extent of surgical resection important? Surgery 1988; 104: 954-62. 4. Cady B, Rossi R. An expanded view of risk-group definition in differentiated thyroid carcinoma. Surgery 1988; 104: 947-53.
In Reaponse:
The following are my responses to the questions raised by Drs. Grant, van Heerden, and Hay: 1. The number of patients may have been small, but it was all we had. All of the patients were included so there could not have been any bias. 2. There were no distant metastases and all patients were operated on for cure. The high-risk group consisted of patients who had one or more of the criteria considered adverse, i.e., age, tumor size, metastasis, local invasion, and previous irradiation. All other patients were considered low risk. Although a numerical value was not assigned to each factor and some patients had more than one adverse factor, the results indicate that the subgroups were truly high risk and low risk. 3. Regarding the inexactness of combining all tumor recurrences, I concede that the prognoses for these recurrences differ but my premise is
that all recurrences are undesirable, require treatment, and represent a failure of the original surgery to control the disease. The operation which results in the fewest recurrences or deaths is the best operation. 4. To support their contention that “6 of the authors’ 20 patients (30%) who underwent ‘total thyroidectomy’ required I- 131 ablation implies significant residual uptake in the neck, and no scan data are provided on the remaining 14 patients,” they have cited three articles, two of which were written by their own unit. One of these [I] represents 860 patients treated from 1946 to 1970 and states “only 3% of patients underwent postoperative radioiodine ablation.” The other paper [2] represents 1,039 patients treated from 1946 to 1975 and states “postoperative 113’ scans were rarely obtained during this period.” Neither article provided scan data on these or their remaining patients. I do not believe that six ab lations in this group is unusual or detracts from the premise that total thyroidectomy is a better procedure. 5. The operative reports were studied and the lesser procedures consisted of subtotal, near-total, or lobectomy plus contralateral thyroid tissue. As the thyroid gland has no anatomic subdivisions, one can only estimate the amount of tissue the op erating surgeon left behind. Exactness is impossible. In both of the references cited [1,2], which were written by them, near-total and subtotal thyroidectomies were placed in the same group for statistical purposes. 6. They state that “convincing data have been published which is in direct contradiction” [1-31 to the conclusion that total thyroidectomy is superior to near-total thyroidectomy with respect to cause-specific mortality, local recurrence, or distant metastases. The first article cited [I] was a comparison of total thyroidectomy versus bilateral subtotal or neartotal thyroidectomy for high-risk tumors. Although there was a lower percentage of survivors in the total thyroidectomy group, the article stated that the AGES score for the total thyroidectomy group was sig-
nificantly higher and therefore this group had more aggressive disease. The second reference cited [2] was a comparison of recurrence rates in high- and low-risk patients. In the low-risk group, less than 2% of 131 total thyroidectomy patients had recurrences after 30 years, while over 5% of 610 bilateral subtotal or neartotal thyroidectomy patients had recurrences. Of the high-risk group, 52 patients had a near-total or subtotal thyroidectomy with a recurrence rate slightly over 20% after 30 years. There were 25 total thyroidectomy patients in the high-risk group with a recurrence rate slightly over 10% after 30 years. The total reference cited [3] did not present any data comparing total thyroidectomy patients with subtotal or near-total patients. I do not believe the data in these references merit the conclusion that “convincing data have been published that are in direct contradiction” to the statement that the advantages of total thyroidectomy have been well documented. 7. Other than one patient who was discussed in the original article, there were no postoperative complications. This “paucity of data” was the reason for writing the article. Grant et al [2] have stated that “resistance to routinely performing total thyroidectomy stems principally from its risks.” I disagree with their statement. I believe the conclusion that the average properly trained surgeon possesses the necessary skill to perform a total thyroidectomy without significant complications is valid. Capt. Robert E. Arnold, MD, FACS Naval Amphibious Base Little Creek, VA 1. Hay ID, Grant CS, Taylor WF, McConahey WM. Ipsilateral lobectomy versus bilateral lobar resection in papillary thyroid carcinoma: a retrospective analysis of surgical outcome using a novel prognostic scoring system. Surgery 1987; 102: 1088-95. 2. Grant CS, Hay ID, Cough IR, Bergstralh EJ, Goellner JR, McConahey WM. Local recurrence in papillary thyroid carcinoma: is extent of surgical resection important? Surgery 1988; 104: 954-62. 3. Cady B, Rossi R. An expanded view of risk-group definition in differentiated thyroid carcinoma. Surgery 1988; 104: 947-53.
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