Respiration 37: 346-351 (1979)
Giant Fibrous Pleural Mesothelioma Associated with Myocardial Restriction and Hypoglycemia Daniel O. Kniznik, A quites J. Roncoroni, Moisés Rosenberg, Gloria Olmedo and Hector J. Cohen Centro Nacional de Rehabilitación Respiratoria ‘Maria Ferrer’ and ‘Ramos Mejia’ Hospital, Buenos Aires
Key Words. Fibrous mesothelioma • Pleural mesothelioma ■Giant mesothelioma • Myocardial restriction • Tumor hypoglycemia Abstract. A giant pleural fibrous mesothelioma was the cause of severe nonobstructive ventilatory incapacity, myocardial restriction with congestive failure and hypoglycemic episodes in a 58-year-old man. Surgical resection resulted in complete recovery of respira tory function and disappearance of hypoglycemic episodes.
Mesothelioma is the more common pri mary pleural tumor, it appears in the right or left hemithorax, more frequently in pa tients 40-60 years old, and it is sex indiffer ent [1], While the diffuse malignant variety originates usually in the parietal pleura the benign solitary version has an indifferent lo cation. According to Shabanah and Sayegh [1] fibrous tumors originate at the mesothe lioma surface. Small tumors are usually asymptomatic and they are observed in chest X-ray surveys or at necropsy. Extrathoracic symptoms: pain, rigidity, articular swelling and even the Bamberger-Marie syndrome have been described occasionally however [I]. The clinical syndrome of the
solitary tumors was reviewed by Claggett et al. [2]. Dyspnea was present in large tumors associated with compression atelectasis, su perior vena cava obstruction or hemody namic compromise.
Case Report A 58-year-old man was admitted, referred from another hospital, complaining of severe ef fort dyspnea appearing some months before, which increasingly incapacitated the patient to mi nor efforts. Simultaneously he noted bilateral an kle swelling and occasional palpitations. A few months later, episodes of profuse sweating and psychomotor excitation were noted, disappearing promptly after intravenous hypertonic glucose injection. Past history revealed hemoptysis 30 years before which was attributed to left lung le-
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Introduction
Giant Fibrous Mesothelioma
347
50
Fig. 2. From top to bottom: electrocardiogram; right ventricular pressure tracing, showing dip and high end-diastolic plateau. Calibration lines; 0-25 and 50 mm Hg.
Fig. 1. Chest roentgenogram on admission.
Time, min
F'ig. 3. Preoperalivc (▲) and postoperative ( • ) blood glucose and insulin levels before and after glucose administration.
tap was repeatedly negative. The electrocar diogram showed diffuse decrease in potential am plitude and first degree A-V block. The white blood cell count was 8,500 cells/mms with a nor mal differential. Electrolytes and urinalysis were normal. Hemoglobin was 12 g°/o. Arterial blood gas analysis revealed PCO,: 35 mm Hg. pH: 7.42, POa: 58 mm Hg. A-a POz: 48 mm Hg. Total plasma protein was 6.57 g%, albumin: 4.35 g%, «,-globulin: 0.21, 0.38, /J: 0.56, y\ 1.07 g%>
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sions of undetermined origin. On admission the patient looked severely ill, with dyspnea at small efforts which made speech difficult. Gross edema of both legs extended up to the thighs. Marked bi lateral jugular vein distention, with systolic col lapse, reached up to the level of the gonion. Forced inspiration did not provoke expansion of the left hemithorax. Dullness on percussion was found over it and along the dorsal spine. Breath sounds were abolished over the same side. Cardiac apical thrust could not be felt, while sounds were displaced to the right and normal except for the presence of an S4. Blood pressure was 120/80 mm Hg. there was no pulsus paradoxus. Under the left costal margin and over the same flank an ill-de fined mass wtih posterior contact under bimanual palpation was observed. A thorax roentgenogram (fig. 1) showed complete opacity on the left side with mediastinal displacement to the right. Pleural
Kniznik/Roncoroni/Rosenberg/Olmedo/Cohen
348
Blood urea was 34 mg% and glucose: 60 mg%. Bilirubin was 0.78 mg%, cholesterol 177 mg% and alkaline phosphatase 43 mU/ml (normal values: 20 to 48 mU/ml). Forced vital capacity (FVC) was: 1.10 (34%), forced expiratory volume in 1 sec (FEV,): 0.90 liters (36“/o), FEV,/FVC: 0.82, maxi mal midexpiratory flow (MMEF): 0.89 liters/sec (30%). Right heart pressures in mm Hg were: atrium mean 13, ventricle: systolic 40, end-diastolic 15; pulmonary artery: systolic 40, diastolic 18, mean 26; pulmonary wedge 15. The ventricular pressure tracing showed a definite dip followed by a high end-diastolic plateau (fig. 2). On bronchos copy there was rightwards tracheal displacement and external compression of the left main bron chus. Percutaneous left thoracic biopsy with a trephine needle showed adult fibroblastic tissue without atypical cells or mitosis. An episode of mental confusion coincided with blood sugar levels of 16mg% and was quickly re
verted by hypertonic glucose infusion. A diabetic type blood sugar tolerance curve was accompanied (fig. 3) by low blood insulin levels (serum immunoreactive insulin). At surgery a massive well-delimitated extrapulmonary tumor was found occupying the left pleural space with vascularized adhesions to the chest wall. The left lung was collapsed but ex panded after removal of the mass, except the left lower lobe which was resected. The surgical speci men consisted of an encapsulated mass (fig. 4) of 28 X 16 X 23 cm weighing 4.9 kg. The external surface was glistening and smooth except in a small area which was the site of adherence to the parietal pleura. The cut surface was firm and ir regularly lobulated by bands of yellowish whitecolored tissue. These lobules were either hard and fibrotic or softer and gelatinous. Hemorrhage and necrosis was seen in others. Microscopy showed mature, closely packed, proliferating fibroblasts
Downloaded by: Nagoya University 133.6.82.173 - 1/15/2019 4:36:45 AM
Fig. 4. Surgically removed tumor.
Giant Fibrous Mesothelioma
__50
Fig. 5. Postoperative right ventricular pressure tracing. See details in figure 2.
sometimes arranged in whorls. In some areas fibril bundles predominated over cells. Dense collagen tissue was present in others. Some less mature cells with large, hyperchromatic nuclei and occa sional mitosis were also seen. The pathology diag nosis was benign pleural fibrous mesothelioma. The resected pulmonary lobe showed gross and microscopic changes of chronic atelectasis. The postoperative course required pleural drainage during a few weeks because of inade quate lung expansion. Glucose tolerance curve re covered normal values with adequate insulin levels (fig. 3). Since the abdominal mass disappeared after surgery it was attributed to tumor palpation through the left diaphragm. Ventilatory capacity recovered partially with FVC: 2.20 liters (60%) FEV,: 1.85 liters (74“/») FEV./FVC: 0.84. and MMEF: 1.60 liters/sec (53%). The right ventricular pressure tracing acquired a normal contour and end-diastolic level (fig. 5). Pressures in mm Hg were: ventricle: systolic 25, end-diastolic: 2; pul monary artery: systolic 25, diastolic 7, mean 13; pulmonary wedge 5. The patient left the hospital and remains in good health after 16 months.
Comment The outstanding symptoms in our patient were those of congestive heart failure, non obstructive ventilatory incapacity and hy poglycemic episodes. Increase in right heart pressures, with nearly similar diastolic lev els plus the dip and plateau ventricular pressure curve tracing, suggested constric tive pericarditis or myocardial restriction. This last possibility was not supported by the right ventriculogram which showed nor mal contractility. During surgery a normal pericardium was visualized. Since hemody namic recovery was complete the preopera tive pattern may be attributed to compres sion by a rigid tumor of right heart cham bers. In 1930, Doege [3] and Poller [4] de scribed hypoglycemia associated with extrapancreatic tumors. This condition was pre sent in about 200 patients [5] with fibrosar comas, carcinoma, hepatoma or fibroma in cluding only 10 with pleural mesothelioma [6J. It is noteworthy that hypoglycemia was not mentioned, however, in the 150 cases reported by Shabanah and Sayegh [1]. Extrapancreatic intrathoracic tumors produc ing hypoglycemia are easily differentiated, by its size and localization, from insulin pro ducing pancreatic tumors. Hypoglycemia of extrapancreatic tumors has been attributed to several mechanisms [ 6 ]:
(I) Increased glucose consumption. It has been estimated that some parenchymal tumors may require 200-300 g/kg/day. This amount is not usually sufficient to account for the observed hypoglycemia (except with very big masses) since some patients needed up to 600 g of glucose infusion, plus usual diet, to maintain normal blood glucose [6J.
Downloaded by: Nagoya University 133.6.82.173 - 1/15/2019 4:36:45 AM
3
349
Increased sugar consumption could occur at the tumor itself by effect of insulin or insulin-like substances manufactured by the tu mor cells. It has also been suggested that these tumors are ATP depleted due to high protein synthesis. Lack of sufficient ATP inhibition of phosphofructokinase may fa vor glycolysis. It is also possible that these tumors may not need insulin for glucose uti lization. (2) Ectopic insulin secretion has been observed in a patient with fibrosarcoma [7] and in another with a hepatic metastasis of an undifferentiated bronchogenic carcinoma [8] but has not been found in the mesothe lioma [6J. Nonsuppressible insulin-like ac tivity in serum and tumor extract was pre sent in a patient with an abdominal leio myosarcoma [5]. (3) Inhibition of gluconeogenesis and lipolysis. It has been shown [9] that L-tryptophan is capable of inhibiting the enzyme phosphoenol-pyruvate carboxykinase and so depresses gluconeogenesis; also that a metabolite of L -tryptophan (nicotinic acid) inhibits lipolysis. Silverstein et al. [10] found an increase in tryptophan and nico tinic acid blood levels in 3 patients with extrapancreatic tumors associated with hypo glycemia. They also observed that indole ac ids induce hypoglycemia in alloxan-treated rats. Recently, Megyesi et al. [11] found, in 5 patients out of 7 with extrapancreatic tu mors and hypoglycemia, increased plasma levels of a purified peptide. NSILA-S (non suppressible insulin-like activity soluble in acid ethanol). Plasma insulin was decreased in this pa tient proportionately to glucose levels. On one occasion, during extreme hypoglycemia (8 mg%>), insulin was not present in plas ma. These are facts demonstrative of insulin-
Kniznik/Roncoroni Rosenberg/Olmcdo/( ohen
independent hypoglycemia and preserva tion of the homeostatic glucose-insulin ser vomechanism. A glucose tolerance curve showing late hyperglycemia may depend on a poor insulin response, similar to that pre sent in starving normal people. At the same time, when this type of curve is found, ex cessive insulin activity may be dismissed as the cause of the hypoglycemic episodes. The risks of major surgery in a patient in the se vere condition reported cannot be overem phasized. Surgical resection of the tumor re sulted, however, in complete recovery of normal life.
Acknowledgement The authors thank Dr. Juan Cresta for the in sulin radioimmune assays and Dr. //. Mogutlevsky and Dr. R. Rios for the hemodynamic studies.
References 1 Shabanah. F. M. and Sayegh, S. F.: Solitary (localized) pleural mesothelioma. Chest 60: 558 (1971). 2 Claggett, O. T.; McDonald, J. R., and Schmidt, H. VV.: Localized fibrous mesothelioma of the pleura. J. thorac. Surg. 24: 213 (1952). 3 Doege. K. W.: Fibrosarcoma of the mediastin um. Ann. Surg. 92: 955 (1930). 4 Potter, R. P.: Intrathoracic tumors: case re port. Radiology 14: 60 (1930). 5 Chandalia. H. B. and Boshcll. B. R.: Hypogly cemia associated with extrapancreatic tumors. Archs intern. Med. 129: 447 (1972). 6 Nelson, R.: Burman, S. O.; Kiani, R.; Chertow, B. S.: Shah. J.. and Cantave. I.: Hypoglycemic coma associated with benign pleural mesothe lioma. J. thorac. cardiovasc. Surg. 69: 306 (1975). 7 August, J. T. and Hyatt. H.: Severe hypogly cemia secondary to a non-pancreatic fibrosar coma with insulin activity. New Engl. J. Med. 258: 17 (1958).
Downloaded by: Nagoya University 133.6.82.173 - 1/15/2019 4:36:45 AM
350
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Giant Fibrous Mesothelioma
pressible insulin-like activity soluble in acidethanol (NSILA-s) in patients with hypoglyce mia and extrapancreatic tumors: application of a new radioreceptor assay. Abstract. 197. 66th Annu. Meet. Arner. Soc. Clin. Invest., 1974, p. 52A.
Received: June 21, 1978 Accepted: September 18, 1978 A. Roncoroni, MD, Centro Nacional de Rehabilitación Respiratoria ‘María Ferrcr’, E. Finochietto 849, Buenos Aires, 1272 (Argentina)
Downloaded by: Nagoya University 133.6.82.173 - 1/15/2019 4:36:45 AM
8 Unger, R. H.; Lochner, J. D., and Eisentraut. A. M.: Identification of insulin and glucagon in a bronchogenic metastasis. J. clin. Endocr. 24: 823 (1964). 9 Ray, P. D.; Foster, D. O., and Lardy, H. A.: Paths of carbon in gluconeogenesis and lipogcnesis. IV. Inhibition by /-tryptophan of hepatic gluconeogenesis at the level of phosphoenol pyruvate formation. J. biol. Chem. 241: 3904 (1966). 10 Silverstcin, M. N.; Wakim. K. G.. and Bahn, R. C.: Tryptophan metabolites in hypoglyce mia associated with neoplasia. Cancer 19: 2024 (1966). 11 Megyesi, K.; Kahn. C. R.; Roth, J.; Gorden, P., and Neville, D. M., jr.: Elevated nonsup-
Giant Fibrous Pleural Mesothelioma Associated with Myocardial Restriction and Hypoglycemia Daniel O. Kniznik, A quites J. Roncoroni, Moisés Rosenberg, Gloria Olmedo and Hector J. Cohen Centro Nacional de Rehabilitación Respiratoria ‘Maria Ferrer’ and ‘Ramos Mejia’ Hospital, Buenos Aires
Key Words. Fibrous mesothelioma • Pleural mesothelioma ■Giant mesothelioma • Myocardial restriction • Tumor hypoglycemia Abstract. A giant pleural fibrous mesothelioma was the cause of severe nonobstructive ventilatory incapacity, myocardial restriction with congestive failure and hypoglycemic episodes in a 58-year-old man. Surgical resection resulted in complete recovery of respira tory function and disappearance of hypoglycemic episodes.
Mesothelioma is the more common pri mary pleural tumor, it appears in the right or left hemithorax, more frequently in pa tients 40-60 years old, and it is sex indiffer ent [1], While the diffuse malignant variety originates usually in the parietal pleura the benign solitary version has an indifferent lo cation. According to Shabanah and Sayegh [1] fibrous tumors originate at the mesothe lioma surface. Small tumors are usually asymptomatic and they are observed in chest X-ray surveys or at necropsy. Extrathoracic symptoms: pain, rigidity, articular swelling and even the Bamberger-Marie syndrome have been described occasionally however [I]. The clinical syndrome of the
solitary tumors was reviewed by Claggett et al. [2]. Dyspnea was present in large tumors associated with compression atelectasis, su perior vena cava obstruction or hemody namic compromise.
Case Report A 58-year-old man was admitted, referred from another hospital, complaining of severe ef fort dyspnea appearing some months before, which increasingly incapacitated the patient to mi nor efforts. Simultaneously he noted bilateral an kle swelling and occasional palpitations. A few months later, episodes of profuse sweating and psychomotor excitation were noted, disappearing promptly after intravenous hypertonic glucose injection. Past history revealed hemoptysis 30 years before which was attributed to left lung le-
Downloaded by: Nagoya University 133.6.82.173 - 1/15/2019 4:36:45 AM
Introduction
Giant Fibrous Mesothelioma
347
50
Fig. 2. From top to bottom: electrocardiogram; right ventricular pressure tracing, showing dip and high end-diastolic plateau. Calibration lines; 0-25 and 50 mm Hg.
Fig. 1. Chest roentgenogram on admission.
Time, min
F'ig. 3. Preoperalivc (▲) and postoperative ( • ) blood glucose and insulin levels before and after glucose administration.
tap was repeatedly negative. The electrocar diogram showed diffuse decrease in potential am plitude and first degree A-V block. The white blood cell count was 8,500 cells/mms with a nor mal differential. Electrolytes and urinalysis were normal. Hemoglobin was 12 g°/o. Arterial blood gas analysis revealed PCO,: 35 mm Hg. pH: 7.42, POa: 58 mm Hg. A-a POz: 48 mm Hg. Total plasma protein was 6.57 g%, albumin: 4.35 g%, «,-globulin: 0.21, 0.38, /J: 0.56, y\ 1.07 g%>
Downloaded by: Nagoya University 133.6.82.173 - 1/15/2019 4:36:45 AM
sions of undetermined origin. On admission the patient looked severely ill, with dyspnea at small efforts which made speech difficult. Gross edema of both legs extended up to the thighs. Marked bi lateral jugular vein distention, with systolic col lapse, reached up to the level of the gonion. Forced inspiration did not provoke expansion of the left hemithorax. Dullness on percussion was found over it and along the dorsal spine. Breath sounds were abolished over the same side. Cardiac apical thrust could not be felt, while sounds were displaced to the right and normal except for the presence of an S4. Blood pressure was 120/80 mm Hg. there was no pulsus paradoxus. Under the left costal margin and over the same flank an ill-de fined mass wtih posterior contact under bimanual palpation was observed. A thorax roentgenogram (fig. 1) showed complete opacity on the left side with mediastinal displacement to the right. Pleural
Kniznik/Roncoroni/Rosenberg/Olmedo/Cohen
348
Blood urea was 34 mg% and glucose: 60 mg%. Bilirubin was 0.78 mg%, cholesterol 177 mg% and alkaline phosphatase 43 mU/ml (normal values: 20 to 48 mU/ml). Forced vital capacity (FVC) was: 1.10 (34%), forced expiratory volume in 1 sec (FEV,): 0.90 liters (36“/o), FEV,/FVC: 0.82, maxi mal midexpiratory flow (MMEF): 0.89 liters/sec (30%). Right heart pressures in mm Hg were: atrium mean 13, ventricle: systolic 40, end-diastolic 15; pulmonary artery: systolic 40, diastolic 18, mean 26; pulmonary wedge 15. The ventricular pressure tracing showed a definite dip followed by a high end-diastolic plateau (fig. 2). On bronchos copy there was rightwards tracheal displacement and external compression of the left main bron chus. Percutaneous left thoracic biopsy with a trephine needle showed adult fibroblastic tissue without atypical cells or mitosis. An episode of mental confusion coincided with blood sugar levels of 16mg% and was quickly re
verted by hypertonic glucose infusion. A diabetic type blood sugar tolerance curve was accompanied (fig. 3) by low blood insulin levels (serum immunoreactive insulin). At surgery a massive well-delimitated extrapulmonary tumor was found occupying the left pleural space with vascularized adhesions to the chest wall. The left lung was collapsed but ex panded after removal of the mass, except the left lower lobe which was resected. The surgical speci men consisted of an encapsulated mass (fig. 4) of 28 X 16 X 23 cm weighing 4.9 kg. The external surface was glistening and smooth except in a small area which was the site of adherence to the parietal pleura. The cut surface was firm and ir regularly lobulated by bands of yellowish whitecolored tissue. These lobules were either hard and fibrotic or softer and gelatinous. Hemorrhage and necrosis was seen in others. Microscopy showed mature, closely packed, proliferating fibroblasts
Downloaded by: Nagoya University 133.6.82.173 - 1/15/2019 4:36:45 AM
Fig. 4. Surgically removed tumor.
Giant Fibrous Mesothelioma
__50
Fig. 5. Postoperative right ventricular pressure tracing. See details in figure 2.
sometimes arranged in whorls. In some areas fibril bundles predominated over cells. Dense collagen tissue was present in others. Some less mature cells with large, hyperchromatic nuclei and occa sional mitosis were also seen. The pathology diag nosis was benign pleural fibrous mesothelioma. The resected pulmonary lobe showed gross and microscopic changes of chronic atelectasis. The postoperative course required pleural drainage during a few weeks because of inade quate lung expansion. Glucose tolerance curve re covered normal values with adequate insulin levels (fig. 3). Since the abdominal mass disappeared after surgery it was attributed to tumor palpation through the left diaphragm. Ventilatory capacity recovered partially with FVC: 2.20 liters (60%) FEV,: 1.85 liters (74“/») FEV./FVC: 0.84. and MMEF: 1.60 liters/sec (53%). The right ventricular pressure tracing acquired a normal contour and end-diastolic level (fig. 5). Pressures in mm Hg were: ventricle: systolic 25, end-diastolic: 2; pul monary artery: systolic 25, diastolic 7, mean 13; pulmonary wedge 5. The patient left the hospital and remains in good health after 16 months.
Comment The outstanding symptoms in our patient were those of congestive heart failure, non obstructive ventilatory incapacity and hy poglycemic episodes. Increase in right heart pressures, with nearly similar diastolic lev els plus the dip and plateau ventricular pressure curve tracing, suggested constric tive pericarditis or myocardial restriction. This last possibility was not supported by the right ventriculogram which showed nor mal contractility. During surgery a normal pericardium was visualized. Since hemody namic recovery was complete the preopera tive pattern may be attributed to compres sion by a rigid tumor of right heart cham bers. In 1930, Doege [3] and Poller [4] de scribed hypoglycemia associated with extrapancreatic tumors. This condition was pre sent in about 200 patients [5] with fibrosar comas, carcinoma, hepatoma or fibroma in cluding only 10 with pleural mesothelioma [6J. It is noteworthy that hypoglycemia was not mentioned, however, in the 150 cases reported by Shabanah and Sayegh [1]. Extrapancreatic intrathoracic tumors produc ing hypoglycemia are easily differentiated, by its size and localization, from insulin pro ducing pancreatic tumors. Hypoglycemia of extrapancreatic tumors has been attributed to several mechanisms [ 6 ]:
(I) Increased glucose consumption. It has been estimated that some parenchymal tumors may require 200-300 g/kg/day. This amount is not usually sufficient to account for the observed hypoglycemia (except with very big masses) since some patients needed up to 600 g of glucose infusion, plus usual diet, to maintain normal blood glucose [6J.
Downloaded by: Nagoya University 133.6.82.173 - 1/15/2019 4:36:45 AM
3
349
Increased sugar consumption could occur at the tumor itself by effect of insulin or insulin-like substances manufactured by the tu mor cells. It has also been suggested that these tumors are ATP depleted due to high protein synthesis. Lack of sufficient ATP inhibition of phosphofructokinase may fa vor glycolysis. It is also possible that these tumors may not need insulin for glucose uti lization. (2) Ectopic insulin secretion has been observed in a patient with fibrosarcoma [7] and in another with a hepatic metastasis of an undifferentiated bronchogenic carcinoma [8] but has not been found in the mesothe lioma [6J. Nonsuppressible insulin-like ac tivity in serum and tumor extract was pre sent in a patient with an abdominal leio myosarcoma [5]. (3) Inhibition of gluconeogenesis and lipolysis. It has been shown [9] that L-tryptophan is capable of inhibiting the enzyme phosphoenol-pyruvate carboxykinase and so depresses gluconeogenesis; also that a metabolite of L -tryptophan (nicotinic acid) inhibits lipolysis. Silverstein et al. [10] found an increase in tryptophan and nico tinic acid blood levels in 3 patients with extrapancreatic tumors associated with hypo glycemia. They also observed that indole ac ids induce hypoglycemia in alloxan-treated rats. Recently, Megyesi et al. [11] found, in 5 patients out of 7 with extrapancreatic tu mors and hypoglycemia, increased plasma levels of a purified peptide. NSILA-S (non suppressible insulin-like activity soluble in acid ethanol). Plasma insulin was decreased in this pa tient proportionately to glucose levels. On one occasion, during extreme hypoglycemia (8 mg%>), insulin was not present in plas ma. These are facts demonstrative of insulin-
Kniznik/Roncoroni Rosenberg/Olmcdo/( ohen
independent hypoglycemia and preserva tion of the homeostatic glucose-insulin ser vomechanism. A glucose tolerance curve showing late hyperglycemia may depend on a poor insulin response, similar to that pre sent in starving normal people. At the same time, when this type of curve is found, ex cessive insulin activity may be dismissed as the cause of the hypoglycemic episodes. The risks of major surgery in a patient in the se vere condition reported cannot be overem phasized. Surgical resection of the tumor re sulted, however, in complete recovery of normal life.
Acknowledgement The authors thank Dr. Juan Cresta for the in sulin radioimmune assays and Dr. //. Mogutlevsky and Dr. R. Rios for the hemodynamic studies.
References 1 Shabanah. F. M. and Sayegh, S. F.: Solitary (localized) pleural mesothelioma. Chest 60: 558 (1971). 2 Claggett, O. T.; McDonald, J. R., and Schmidt, H. VV.: Localized fibrous mesothelioma of the pleura. J. thorac. Surg. 24: 213 (1952). 3 Doege. K. W.: Fibrosarcoma of the mediastin um. Ann. Surg. 92: 955 (1930). 4 Potter, R. P.: Intrathoracic tumors: case re port. Radiology 14: 60 (1930). 5 Chandalia. H. B. and Boshcll. B. R.: Hypogly cemia associated with extrapancreatic tumors. Archs intern. Med. 129: 447 (1972). 6 Nelson, R.: Burman, S. O.; Kiani, R.; Chertow, B. S.: Shah. J.. and Cantave. I.: Hypoglycemic coma associated with benign pleural mesothe lioma. J. thorac. cardiovasc. Surg. 69: 306 (1975). 7 August, J. T. and Hyatt. H.: Severe hypogly cemia secondary to a non-pancreatic fibrosar coma with insulin activity. New Engl. J. Med. 258: 17 (1958).
Downloaded by: Nagoya University 133.6.82.173 - 1/15/2019 4:36:45 AM
350
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Giant Fibrous Mesothelioma
pressible insulin-like activity soluble in acidethanol (NSILA-s) in patients with hypoglyce mia and extrapancreatic tumors: application of a new radioreceptor assay. Abstract. 197. 66th Annu. Meet. Arner. Soc. Clin. Invest., 1974, p. 52A.
Received: June 21, 1978 Accepted: September 18, 1978 A. Roncoroni, MD, Centro Nacional de Rehabilitación Respiratoria ‘María Ferrcr’, E. Finochietto 849, Buenos Aires, 1272 (Argentina)
Downloaded by: Nagoya University 133.6.82.173 - 1/15/2019 4:36:45 AM
8 Unger, R. H.; Lochner, J. D., and Eisentraut. A. M.: Identification of insulin and glucagon in a bronchogenic metastasis. J. clin. Endocr. 24: 823 (1964). 9 Ray, P. D.; Foster, D. O., and Lardy, H. A.: Paths of carbon in gluconeogenesis and lipogcnesis. IV. Inhibition by /-tryptophan of hepatic gluconeogenesis at the level of phosphoenol pyruvate formation. J. biol. Chem. 241: 3904 (1966). 10 Silverstcin, M. N.; Wakim. K. G.. and Bahn, R. C.: Tryptophan metabolites in hypoglyce mia associated with neoplasia. Cancer 19: 2024 (1966). 11 Megyesi, K.; Kahn. C. R.; Roth, J.; Gorden, P., and Neville, D. M., jr.: Elevated nonsup-
