Document 0JO60rYmxjgLx2qQpw3EwoDVV

130 . Aijuials New York Academy of Sciences 18. Dugois, P., P. Amolard, B. De Bicnicourt 4 J. Leorand. 1972. Acropaihle polyvinylique profcssionnelle. Bull. Soc. Franc. Dermatol. Syphiligr. 79: 197. 19. Eckarot, R. E 4 R. HlNOIN. 1973. The health hazards of plastics. J. Occupa tional hied. 13: 808. 30. Edmondson. H. A., R. L. Peters. H. H. Frankel 4 S. Borowski. 1967. The early stage of liver injury In (he alcoholics. Medicine 46: 119. 31. Eurofaciiumie. 1972. Handelsblait GmbH. Dilsseliiorf, West Germany. \c -51--KaIRIHI I I T. 1937 l"1||lrll Huclenln^LjlpJ-di^_p.^ AUj|llBm^e--WilHne-- I -CompanyrBnliimore, Md. 33. Filatova, V. S. 4 E. Sll. Gronseero. 1937. Sanitarno-gigienifeskic usloviya truda v proilvodstvc polikhlorvinilovoi smolyi l meryt ikh ozdorovltniya. Gigiena Sanit. No. 1: 38. 54. Filatova, V. S,, L. I. Balakhonova 4 E. Sii. Gronsdero. 1958. Gigicnieeskaya kharak(eris(ika proizvodstva khloristovo vinila. .Gigiena Truda Prof. Zabolevaniya 2(1): 53. Filatova, V. S., E. Sii. Gronsbero, N. A. Smirnova, E. A. Stulova 4 I.'V. Oresckevic. 1965. Voprosyi gigienyi truda i sostoyanie zdorov'ya rabotikh, zanyatyikh no proizvodstva laieksnovo poitvinilkhlorida. Gigiena Truda Prof. Zaboleva niya 9: 9. 56. Filatova, V. S. 4 V. A. AntoNYUZJIENXO. 1971. Gigieniieskiye usloviya truda I professionat'naya ubotevaemosl1 raboiikh proizvodstva suspenzionnovo poli vinilkhlorida v dinamike za ryad Jel. Gigiena Truda Prof. Zabolevaniya 15(4): 32. 57. Fischer, J., II. Mundsciienk 4 R. Wolf. 1965. Milzszintlgraphie mil l-Bromo- mercuri ("'ll v)-lhynroxypiopan (BMHP). Forlschr. Gebiete Roenlgenstrahlen i-iuklcarmcd. 103s 349. 58. FtscuaR, I., R. Wolf 4 H. Gamm. 1973. Die Milzszintlgraphie. Dtsch. Arztebl. No. 7:401. P(,-J jC- y) i iqaq T..T.rr nf liver in niiMw ryf [hr Thai T 1i UIIT PH iNAediN-Jt-D.1 LippniCTJtt Gurupari). Philadelphia, Par 60. Gitsios, C. T. 1971. Acro-osleolysis in PVC workers. Med. Bull. Stand. Oil Co. 31(1); 49. 6;. Gunther, O. 1956. Die Kunststolfe und ihre arbeitsmedizinische Oedeuiung. Zcntr. Arbeitsmed. 6: 156. 62. IIabrii, D. K. 1953. Health problems In the manufacture and use o( plastics. Brit. 1. Ind. Med. 10! 255. 6). Harris, D. K. 4 W. G, F. Aoams. 1967. Acro-ostcolysis occurring in men engaged in the polymerization of vinyl chloride. Brit. Med. 1. it 712. 64. Hensciiler, D., Ed. 1972/1973. Gesundheitsschldliche Arbeitsslofle. Toxlkologitch-crbcilimcdiilnlschc Uegrllndungen von MAK-Werten (Maximale Arbeils- plaiz-Konzemrationen). VerlagChemie. Weinheim, West Germany. "7 65. IIerrle, K. 1963. Potyvinylchlorid. In Ullmanns Encyklopadie der lechnijchen Chentie. W. Foerst, Ed. 3rd edit. Vol. 14. Urban 4 Schwarzenberg. Milnchcn, West Germany. 66. Hervieux 4 Tessier. 1959. Quclques observations d'exposition el d'inloUrance rux d6riv6s vinyliques et aux rfstnes fthoxyliqucs. Aren. Maladies l'ro(ess. 20t 61. 67. Iber, F. L. 1970. Portal hypertension in the presence of normal liver morphology. Ann. N.Y. Acad. Sci. 170(1): M5. 68. International Labour Office. 1971. Encyclopaedia o( Occupational Health and Safety. Geneva, Switzerland. Vol. I: 387. 69. International Labour Office. 1972. Encyclopaedia ol Occupational Health and Safely. Geneva, Switzerland. Vol. If: 1467. 4^ 70; Irish, P. Pi IP63 -Ualngenuirri hydrocarbons; I. EHphatia. In Industrial Hygiene l-UIr '+T"TTin u,4rlii TviifHfyi PrWi FniMS h P, n, C-U Tnlrr.- MiuiLe-Pobltjhetj; New Yutk", I4DT! * 71. Uvitt, N. B. 197C. Clinical and experimental aspects ol sulphobromophthaleln and related compounds. In Progress in Liver Disease. H. Popper 4 F. Schaffncr, Eds. Vol. lit. Crsne 4 Stratton. New York, N.Y. 72. luoAtt,D., A. E. M. McLean 4 E. K. McLean. 1970. Biochemical mechanisms of liver injury. Am. 1. Med. 49t 609. 71. JilttE, 3. 4 C. E. Lance. 1972. Sklcrodermlcartlge Hsulverknderungen, Raynaud- Syndrom ur.d Aktooueolysen bet Arbeitcrn der PVC-herstellcndcn Industrie. Deut. Med. Vcciischr. 97: 1922. oe?z gsi9oaa Marstcllcr el ol.: Splenomegalies Liver Disease 131 74. Kelly, R. E. 1973, Vinyl chloride and acroostcolysis. J. Occupational Med. lSr 858. , 75. Klatskin, G. 1969. Toxic and drug induced hepatitis. In Diseases of the Liver. L. Schid, Ed. 3rd edit. 1. B. Lippincott Company. Philadelphia, Pa. jw mi. iPjySMBWP111*'^ ||fM||M im" 77. Kluoe, T., H. Sommerschild 4 A. Flatmark.Q970j Sinusoidal portal hyperten- ^^^^enlal measurements for workers exposed to vinyl chloride. Am. Ind. Hyg. Assoc. J. 33: 19. 79. Lance, C.-E., S. JUiie, G. Stein 4 G. Vcltman. 1974, Die logenannie Vinyl- ' chlorid-Krankheit--cine berufsbedingie Sysiemskterose7 Inlem. Arch. Arbefts- med. 32t I. 80. Leake, C. D. 1934. The role of pharmacology in (he development of ideal anes thesia. J. Am. Med. Assoc. 102: 1. ', 91 IrruiHi- P,i 1966 Ct\rmi ...... ..j i r-ix,....i.,.-rT.. i(,.nmtii|if- M^m-ry gqq --UUM-SemTuriyr 82. LfLvre, M. 1. 1972. Internationales Symposion der Wcrksiirzte der Chemischen Industrie, 27-29 April 1972, Ludwigshaien. As cited in Stein el ol., 1973. 83. Lehmann, K. B. 4 F. Flury, Eds. 1938. Toxikologie und Hygiene der techni- - schen Losungsmittel. Julius Springer. Berlin, Germany. 84. Lester, D., L, A. Greenberg 4 W. R. Adams. 1963., Effects of single and re peated exposures of humans and rats to vinyl chloride. Am. Ind. Hyg. Assoc. J. 24: 265. 85. L:ndner, H. 1973. Laparoscopy in alcohol-induced liver disease. Gastroenterology 64t 842. 86. MacSween, R. N. M., J. M. Vetters, S. K. Ross, J. Ferguson, J. M. John stone 4 A. T. Sanoison. 1973. Hacmaogio-cndoihelial sarcoma of the liver. J. Pathol. 109. 39, W. Maznai. R. E.~4 R. L,~a;ECHuu. 196 h Industrial, Toaraolagp and Dumnlulogy in Ilia PruduUiutt' and^PtDLES'SllIL' uf Pla-iliur.-EHeviar Publishim fhjuimiiT. /c_ 1 88. Maltoni, C., M. Cresfi 4 P. 1. R. Burch, Eds. 1973. II International Symposium on Cancer Detection and Prevention, Bologna, April 9-12, 1973. Excarpta Medica lot. Congr. Ser. No. 275. 89. Marin, A.. 1. Strauss, R, Miciiiels, I. P. Benoit, R. Baltie 4 C. Pierre. 1967. .7190. Acocnroir-eos'letio"Rl"yhsucmda'tol.srmlgctne Markowitz. S. S., C. 1. pro/' $ _ .fljl s/ifcTrraI1Ov9aX6l7H)).pnRti-esuve.nRDillIt.1u.Mmlaa.IlL. l31gA4u,:e3nF4n0rs. ncalse -etiiiere 4 M. S. Kerzner. 1912. Oc- cupational acroosleoly >1.106:219. 91 Marsteller, H. ]., W. 10 IGller, S. JUiie, C. E. Lanoe, H. 0. Roiiner 4 G. VELTMAi -loxtsche Leberschiiden bei Arbeitcrn in der PVC-Produktion. schr. 98:2311. 92. Mastroaiatteo, E., A. M tie 4 H. Danzioer. I960. Acute in- halation toxicity ol viny ttory animals. Am. lad. Hyg. Assoc. H m1. Si 394; Dull. liyg. 36;, 91 hLirras,.54 B--IS6,9 Qcct The Williams--4-Wilkins fiotlipJliy."fipoo /C. Ballimnra. Mil wm 94. McCord, C. P. 1970. A nei 12: 234. HI Cft f95. Mixkelsen, W. P., 11. A. E Reynolds. 1965. Extra- ar. SI ?(hepatoportal sclerosis). An. 96. Misoeld, V.. H. J. Stolfma Vinylchlorid-Polymerisate u 48: 425. 97. Morris, }. S., T. Htut 4 A. E. Ann. Rheumatic Diseases 31: H H q :ase is born. J. Occupational Med. 0 Peters, A. G. Reoeker 4 T. B. tal hypertension without cirrhosis i> . 1973. Zur Inloxikalion durch IcilstofTe. Z. Haul Geschlechlskr. t <3>adcrma and portal hypertension. 98. Nemesinr, A, 4 W. J. Fink. 19oi. Neoplasms of the liver following injection of thorotrast. Am. 1. Clin. Pathol. 35: 422. 99. Outtel, II. 1963. Gcwerbejoxikofogie und Physiologic einzclncr Polymcrlsaic. Polymerisale chlorierter Atliylcne. In Ullmanns Encyklopadie der lechnischtn Sinusoidal portal hypertension TROND KLUGE, M.D. HENRICH SOMMERSGH1LD, M.D. AUDUN FLATMARK, M.D. OSLO, NOSWAY From the Snrgitti Deportment 4 (Heed: B. Fretkeim), the Fedielric Surgieel Struicc (Heed: 0. Knutrud), the Univenity Institute of f<Jkoi|tfa{ Anetomy (Iftedt O. Torgotten), sad tk4 Lebortiory of Electron Microscopy (fitted: T. HouigJ, Rikrkerpitelet (University Clinic) :! w i! O 1 U> . ON 'i to !| Ol l: "J 3 o-H o --i m o CD -< a O a O "U Z o--4 o m H X o> S >--H rn ru a o 3 >-< 1 CD m jLorUl hypertension in infant* and young adults it mainly of the presimiaoidal type and is caused by portal vein obstruction or con* genital hepatic fibrous. PotUinusoidal ob structions are due to cirrhosis from hepatitis or various rare metabolic disorders. There remains a group of piiiirnu whose jmriitl hypertension is refened to as "idiopathic" because no anatomic lesion can be demon strated. The purpose of the present paper is to present a new type of intrahepattc obstruc tion, localized to the hepatic sinusoids and perisinusoidal areas. CASE REPORTS Csss 1. E. 0. F., a 7-year-old boy, product of a normal pregnancy sad delivery, bad a normal nee* natal period. At 10 mood* of age, he developed an acute abdominal condition, and emergency lap arotomy revealed a marked mesenteric adenitis whose nature was obscure. During the following two yean, he experienced several episodes of mel- eoa and the spleen became enlarged. At the age of S be was admitted because of hematemesis, melena, and anemia. A barium swallow demon strated esophageal varices (Fig. Id), and be bad . splenomegaly with signs of hypenplenism. Splenoportograms (Fig. IS) revealed patent . splenic and portal veins and several portosystemic anastomoses. The intrahepatic portal vein radicals were slightly irregular and more closely approxi- SubstUtod ter publkstkw July 7, (969; S*t. , 1969. Authors' addrsa: Bttsfcospitetot, Odo I, Norway, 294 SURGERY IS70 mated than usual, and the radiographs were con sidered indicative of a hepatic cirrhosis. Splenic pulp pressure was above 60 cm. H*0, For the next three years, there were a few mild episodes of melena, but at the age of 61/% yean the patient was readmitted because of severe hemorrhage. At this time he had ascites, splenomegaly, hepatomegaly, thrombocytopenia (311,000), hy|Mi|rutaiitcitii* (!Mf dm. percent), and a PP (prothrombin-proconvertin) reading of 70 percent. Results of tests for erythrocyte sedi mentation rate (ESR), serum glutamic oxalacetic transaminase (SCOT), serum glutamic pyruvic transaminase (SGPT), thymol, and serum elec trophoresis were within normal values. Due to acute deterioration, with increasing ascites and abdominal pain, be was again operated upon as an emergency procedure. Them were numerous intrsperitaneaJ adhesions with dilated vessels. Surprisingly, the Uver had a normal ap pearance and consistency. The spleen, which weighed 440 grams, was removed. Direct splenic vein pressure was IS cm. H0 and identical with the central venous pressure (CVP). The pressure was recorded independently by both surgeons, and we consider the result as reliable, but have no explanation for the discrepancy between the trwsoperalive recording and the pressure obtained by tpkaic pulp puncture. The postoperative course was uneventful, with out hemorrhage or other complications. On the eighth day the platelet count was 210,000, end serum proteins also were normal. Celiac arte riography demonstrated a normal arterial supply of the liver and upper gastrointestinal tract. The patient was discharged three weeks after surgery. At follow-up examination three months later, the general condition was considerably Unproved. Vet, 68, No. 2, pp. 294-300 ZOOOiGt'Z Volume 68 Number 2 Sinusoidal portal hypertension' 295 There had been no gastrointestinal bleeding, ascites was barely demonstrable, and the patient had gained weight. Results of laboratory tests were grossly normal. Esophageal varices were still demonstrable by x-ray-examination, but appeared diminished as compared with preoperative radiographs. Case 2. O. 0., a 29-year-old man, had had a normal neonatal period, and there had been no liver disease or hereditary disorders in the family. At the age of 9, he had been operated upon for a perforated appendix with peritonitis. He had experienced episodes of melena at<vages 19 and 27, but was not hospitalized. Heavy hematemesis and melena with syncope led to emergency admission at the age of 29. At this time, an enlarged spleen was detected, and there were slightly abnormal values of the tests for Bromsulphalein (BSP) and alkaline phosphatase. Results of tests for thymol, SGOT, SGPT, and serum electrophoresis were normal. Esophageal varices were clearly demonstrable by x-ray-examination. The portal vein with intra hepatic radicals was normal. Splenic pulp pressure was 30 cm. H0. Arteriography (Fig. 1C) revealed a normal pattern of hepatic arteries. Venography of hepatic veins showed a rapid filling at the central vein level, and a marked shunting between the larger vein radicals (Fig. ID). Recording with the cutheter in wedge position gave a pressure of It (-mi. lf,0 ImiI, Imw;xom of llio pkipm* ive shunting, this may merely represent the CVP in the vena cava. Splenectomy and splenorenal shunt were then performed. The congested spleen weighed 720 grams; otherwise no intra-abdominal disorder was detected. The Uver, in particular, appeared nor mal upon inspection and palpation. Shunt flow at operation was 300 ml. per minute. 11m postoperative course was unremarkable, and the patient waa discharged 13 days after the operation. At follow-up examination four months later, he was in good health aad had not experi enced any episodes of hemorrhage. Results of all laboratory teste were normal, including x-rays of the esophagus. Macroscopic examinations of Cases 1 and 2. At operation, the liver did not exhibit any gross lesions in either case. The surfaces of both lobes were smooth and glistening, aad the parenchyma showed a normal color. Upon thorough palpation, the consistency was normally soft, without nodules, bands, or firmer areas. This observation was sur prising because both case histories and the preoperative x-ray studies were suggestive hepatic cirrhosis. A large, wedge-shaped biopsy specimen, with a depth of 4 cm., was taken from the anterior rupee* of the left lobe in both patients. In Case 2, pieces 2 by 2 mm. from several areas were im mediately immersed in glutaraldehyde and pro cessed for electron microscopy. Light microscopy of Gases 1 and 2. The speci mens were processed according to standard meth ods and sections were stained with hematoxylin and eorifi, van Gicson-elaitin, Masson's trichrome stain, periodic acid-Schiff (PAS), Best's carmine, reticuiin (Wilder), iron-hematoxylin, methyl greeirpyronine, and Congo red. The microscopical pictures in the two cases appeared identical, and will be described together. The specimens presented a normal Uver archi tecture, with well-preserved lobules separated by normal portal triads. The capsule of Gtisson ap peared normal, and there was no Increase In con nective tissue along the portal triads. The portal veins, small arteries, and bile ducts were also nor mal (Fig. 2A), without evidence of fibrosis, bile duct proliferation, or inflammatory reactions. The only abnormal feature of the periportal areas was a moderate dilatation of some lymph vessels. The parenchymal liver cells were normal In all areas (Figs. 2A and 2D), with well-preserved cytoplasm and normal contents of glycogen. There were no signs of degeneration, fatty changes, necrosis, cellular infiltration, giant-cell transforma tion, or pseudolobule formation. The central veins were patent and normally configurated; some had a slightly larger diameter than usual. Upon close examination, a certain iiu'rruso of ijimuwiJv* llssu* elements could be seen around the central veins (Fig. 2fl). By means of specie! staining, this impression was verified, and in several areas the strands of connective tissue could be followed in between the hepatic cells, itmt Is, along the hepatic sinusoids (Figs. 2C and 2D). Thti observation prompted us to investigate the morphology of the sinusoidal/ paraslnuioidal areas by means of electron micros copy, , Electron microscopy of Ceie 2. Specimens were kept in the 2.3 percent glutaraldehyde solu tion for 2 hours at 4* C., postfixed In osmium tetroxide for 4 hours, dehydrated in graded ethanols, and embedded in Epon 812. Thin (0.3 mg) sections for light microscopy were stained with alkaline toluidine blue, and ultrathin (0.1 mg) sections were stained with uranyl acetate and lead citrate and examined in Siemens Elraiskop 1. When examined by electron mkroecopy, the hepatocytes showed a normal appearance with well-preserved cytoplasmic elements (Fig- 3d), and the cell borders were normally configurated. The light microscopic impression of normal portal triads and periportal areas was also verified. The bile canalkuti and their surrounding structures presented the usual morphological picture (Fig. 3d), and there was no iocreuc at connective tis sue in these regions. 296 Klugf, SommttsehUd, and Flatmark Surgery August 1970 BFG36258 Fig. IA. Case 1. Esophageal varices demonstrated on barium swallow. Fig. 10. Case 1. Splenoportogram. Portal vein and intrahepatic portal radicals patent; coronary vein heavily distended with anastomoses to splenoportsl system. Fig. IC. Case 2. Arteriogram o! celiac axis. Nonna) hepatic arterial supply. Fig. 1X>. Case 2. Venography of hepatic vein with catheter in wedge position. Smaller hepatic vein branches visualised but marked shunting between larger hepatic vein radicals. fig, BA. Case 2. Electron micrograph of S normal hepatecftce facing' SC. H separated by IS which are normally configurated. No indication of cellulardamage or intercellular fibrosis. (*13,000.) Fig. 30. Electron micrograph of hepatic sinusoid. Enlarged KC with large LY are lining narrow sinusoid, which contains RBC. Bundles of COL in space of DissX. HC present normal morphology. (*12,000.) Fig. SC. Large sinusoid with perisinusoids! area. LY in enlarged KC seem to make impressions of RBC in sinusoidal lumen. Heavy amounts of COL fibers In perislnusoidal areas. (*12,000.) Fig. 3D. Bundles of COL appear to obliterate space of DissX between HC and sinusoidal lumen. Sickle* shaped RBC inside sinusoid. Large LY within cytoplasm of KC. (*24,000.) .Fig. 2A. Case 1. Light micrograph of portal triad : with normal portal vein branches (BV), arterioles (A), and bile capillaries (BC), (Hematoxylin and roein; xlOO.) Fig. 20. Case 1. Normal architecture of liver lobule around central vein (CVj. Deposits of con nective tissue around margin. (Rctioilin (Wilder); *100.) Fig. 2C. Case 2. Connective tissue elements at periphery of central vein extend along the sinus* oid and between parenchymal cells. Strands of collagen indicated by arrows. (Masson's trichrome; *400.) Fig. 2D. Case 2. Large KupfTer cells (K) along narrow sinusoids. Heavy collagen deposits alone sinusoids clearly outlined (arrows). Farvnchymal cells normal. (Masson; x900.) BFG36259 298 Kluge, Sommerschild, and Flatmark Surgery August 1970 The linugoidal areas, on the other band, dis played definite pathological features. The Kupffer cells appeared markedly enlarged and irregular, with cytoplasmic protrusions into the sinusoids (Figs. 3 and 3C). Hence, the sinusoidal lumina were considerably diminished, and the erythro cytes inside the sinusoids were polygonal, llattencd, or even sickle-shaped (Figs. 3 and 3D). The cytoplasm of the Kupffer cells contained numerous large Inclusions of lysosomal character, surrounded by a triple-layered membrane. Their interior was occupied by aa amorphous matrix of low elec tron density (Figs. 3B and SC). The mito chondria and endoplasmic reticulum appeared normal, whereas the vermiform structures typical of resting Kupffer cells were absent. Platelets were seen adherent to the sinusoidal lining in some areas, but there was no evidence of throm bosis in the sinusoids. The space of Diuf, which normally separates the sinusoidal endothelium from the surface of the hepatocytes, was obliterated in the majority of sections. The space was occupied by heavy deposits of collagen fibers arranged in bundles (Fip. SC and 3D). Accordingly, the distance between the sinusoids and adjacent hepatocytes was considerably increased. This perisinusoids! fibrosis corresponded well to the strands of con nective tissue as observed by light microscopy (Figs. 2C and 2D). The perisinusoidal connective tissue contained some cells identified as fibroblasts and a few macrophages. In general, the cellular elements of this compartment were scarce, and there were no signs of active inflammation. DISCUSSION In the following section the reported ob servations will be related to the already -known causes of portal hypertension. It appears convenient to distinguish between pre- and postsinusoidal flow obstructions.9 Preatnusosda) obstructions. Intrahepatic. Upon x-ray examination, the intrahepatic portal vein radicals appeared slightly irregular but open. This finding might have been consistent with the syn drome of portal fibrosis1 or hepatoportal sclerosis.9 By means of microscopy, however, the intrahepatic portal vein branches were shown to be normal. The presence of open and normal portal radicals also excluded the diagnosis of portal fibrous dysplasia.11 Con genital hepatic fibrosis'*9 is characterized by . the fibrous bands that interweave throughout the liver substance. The histological aspects also arc quite distinctive, the main features being dense fibrosis of die portal areas and proliferation of biJe ducts. Such changes were absent in the present speci mens. Extraliepaltc. Occlusion, sfenosi*. or con genital malformations of the portal vem,u could be excluded with certainty in the pres ent cases. Doth showed a patent jx>itul vein by splenoportography, and there was no sug gestion of cavernous transformation.1* Fur thermore, patent splenic and portal veins were demonstrated at operation. Postsinusoidal obstructions. Intrahepatic. Apart from the inflammatory condition in both cases (see below), there was no suggestion of previous hepatitis in the case histories. None of the patients had experienced jaundice, and results of the liver function tests were grossly normal. The degenerative and reparative changes in post hepatitic cirrhosis were absent from the histological picture. Biliary atresia with cir rhosis also could be ruled out with certainty from the clinical picture and from the find ing of normal biliary radicals. There was no indication of familial hepatic or renal dis ease.9 The various inborn errors of metabolism (hepatolenticular degeneration, galactosemia, tyrosinosis, and the like) were excluded, be cause the parenchymal damage and fibrosis seen in these conditions were lacking. The same view pertains to hereditary telangiec tases, fibrocystic disease, and cystic disease of the liver.9 There was no suggestion of lipodystrophies (Hurler, Gaucher, Niemann-Pick) affecting the liver, and the spleen showed only changes associated with venous congestion. Neither was there any indication of abnormal hepato cellular glycogen storage (von Gierke, Pompe, and others). The intrahepatic ves sels also were examined for collagen disease and amyloid deposits, with negative results. Extrahepatic, Both patients had a normal cardiopulmonary state, and a chronic venous congestion of the liver could be ruled out with certainty. The jjosribilfty of a hepatic vein thrombosis (Budd-Cliiari syndrome)'* t>0006frZ Volume 68 Number 2 Sinusoidal portal hypertension' 289. i was excluded by microscopy and by vciiographic demonstration of patent hepatic veins (Fig. ID). The shunting between some of the hepatic vein radicals, however, might suggest a venous occlusion at a more j>eriphral level, i.e., "mio-ocdunive disease."* Tim condition is characterized by a ccntrilobulur fibrosis and a complete or partial occluKton of the central veins. In the present cases, however, these had a normal or even in creased diameter. Furthermore, the fibrosis was detected only after special staining and by means of repeated examination. Sinusoidal obstructions. In the present study, the electron microscopic examinations verified and extended the observations made by light microscopy, and revealed a triad of anatomic lesions. 1.The Kupffer cells were hypertrophic and contained large cytoplasmic inclusions with the morphological pattern of lysosomes.4 Compared to norma! Kupffer cells, these lysosomes or phagosomes were much larger and less electron dense than usual. Their appearance was not consistent with that of lipodystrophies, and the nature of their con tent could not be established from the mor phological appearance. The general impres sion, however, was that of abnormally en larged Kupffer cells, possibly with signs of hyperactivity. 2. The sinusoidal lumina were consider ably diminished in diameter, owing to the enlargement of the Kupffer cells. In several sections, the sinusoids seemed barely to allow the passage of one erythrocyte. 3. There was a heavy perisinusoidal fibro sis, with increased amount of collagen in the space of DissA, which frequently appeared to be occluded. It is our opinion that these observations may well explain the portal hypertension in the present cases, combined with the angio graphic patterns and the normal liver func tion tests. It is likely, also, that the dilatation of periportal lymphatics may be caused by obliteration of the space of Dissd with im pairment of lymph circulation. Similar observations have not lccn en countered in the available literature. Boyer ami associates' reported on two cam that did not seem to tit into their syndrome of portal fibrosis, since the latter was very moderate. Electron microscopy demonstrated a definite increase of collagen in the space of Oissl, and those two cases may be similar to the syndrome presented in this report. A thorough comparison cannot be made, since the paper by Doyer and associates is devoid ot electron micrographs. The pathogenesis of the present syndrome is at present a matter of speculation. Paren chymal disease, biliary and portal affections, cirrhosis, hepatic congestion and veno-occhtsive disease have all been excluded as causa tive mechanisms. Hepatic damage secondary to shock from esophageal hemorrhage' or secondary to hypersplenism* must be con sidered very unlikely in the present cases. Attention is, however, focused on the history of an acute abdominal condition (mesenterial adenitis?) in Case 1 and an inflammatory peritonitis in Case 2. ft is tempting to suggest the possibility of im munological reactions with affection of the reticuloendothelial system,4 leading to Kupf fer cell proliferation and perisinusoidal fibrosis. SUMMARY Two patients with portal hypertension were operated upon at 7 and 21 years of age, respectively. The portal vein was patent in both cases, and the liver appeared norma) upon gross examination. Light and electron microscopic studies of wedge-shaped biopsy specimens of the liver revealed marked hypertrophy of Kupffer cells and narrowing of the sinusoidal lumina. There was a heavy perisinusoidal fibrosis with obliteration of the space of DissA The hepatic parenchymal cells and the porta) triads were normal. Pre- and postsinusoidal obstruction could be excluded in both pa tients. The observations suggest that the portal hypertension in the present cases is caused by a flow obstruction at the sinusoidal level. These findings seem to add a new aspect to the luthogcncsis of "idiopathic" (xnlal liyikrteiishit. BFG36260 300 Kluge, Sommcrschild, and Ftalmark Surgery August 1970 ADDENDUM After (hit manuscript had been completed, two mart patient* were examined for a similar type of intrahepitic portal hypertension with bleeding esophageal varices. A 9-year-ojd boy and a 6-yearold girl have both been subjected to shunt proce dures for this reason. Both presented slightly compressed intrahepattc vein branches but other* wise normal liver by angiography and macro scopic examination. Light microscopy showed perisinusotdal fibrosis continuous with connective tissue around central veins. The Kupfier cells appeared enlarged and sometimes arranged in larger nests. The girl has now reached the age of seventeen and will be subjected to another shunt operation for recurrent bleeding. Liver specimens from this patient are being processed for electron microscopy. 1 The authors gratefully acknowledge the tech nical assistance received from the Department of Radiology and the Laboratory of Electron Microscopy of the R-ikshdspitalet, Oslo. They also acknowledge with thanks'the help of Mr. Martin Finch, of the Department of Medical Art and Photography at the University of Minnesota, in the arrangement of the illustrative materials. REFERENCES 1. Boyer, J. L. Sen Gupta, K. P., Biswas, S. K., Pal, N. C., Basu MalJick, K. C., Iber, F. L., and Basu, A. K.i Idiopathic portal hyper tension (noncirrbotic portal fibrosis), Ann. Intern. Med. 66: 41, 1967. 2. Iber, F. L., and Maddrey, W. C.; Familial hepatic diseases with portal hypertension with or without cirrhosis, is Popper, H., and Schaffner, E. s Progress in liver diseases, ed. 2, New York, 1965, Grune A Stratton, Inc. 3. Kerr, D. N, S., Harrison, C. V., Sherlock, S., and Milnes Wakcr, R.; Congenital hepatic fibrosis, Quart. J. Med. 30; 91, 1961. 4. Kluge, T., and Hovig, T.: Ultrastructural localisation of Thorotrast in the reticulo endothelial system, Amer. J. Path. 54: 355, 1969. 5. Mikkelsen, W. P., Edmondson, H. A., Peters, R. L., Redcker, A. C., and Reynolds T. B.; Extra- and intrahepatic portal hypertension without cirrhosis (bepatoportal sclerosis), Ann. Surg. 162: 602, 1963. 6. Parker, R. A., and Seal, R. M. E.; Fibrosis of the liver as a congenital anomaly, J. Path. Bact. 71) 339, 1956. 7. Popper, H,, Barka, T., Goidfarb, S., Huttcrer, F., Paronetto, F., Rubin, E., Schaffner, F., Singer, E. J., and Zak, F. G.; Studies on the progression from acute hepatic Injury to fibrosis of the liver, J. Mount Sinai Hosp. N. Y. 29t 152, 1962. 8. Scheuer, P.: Liver biopsy interpretation, London, 1968, Baillitre, Tindall, A Cassell, Ltd. 9. Sherlock, S.: Diseases of the liver and biliary system, ed. 2, New York A London, 1963, Blackwell Scientific Publications. 10. Tank. E. S,, Wallin, V. W., Turcotte, J. G., and Child, C. G.: Surgical management of bleeding gastroesophageal varices in children, Arch. Surg. 98: 451, 1969. 11. Taubert, \V.: Ungew&hnliche Intrahepatische Portadervennderung all Ubrsgcbe ciner portaien Hypertension, Zbl. Allg. Path. 108: 417, 1966. 12. Wilson, K. W., Robinson, D. C., and Hacking, P. M.: Portal hypertension in child hood, Brit. J. Surg. 56; 13, 1969. I SOOiOGVZ Pseudomyxoma peritonei: Case report including in vitro mucolysis J FRANCIS E. ROSATO, M.D.* MURRAY H. SELTZER, M.D.* PHILADELPHIA, PA. From the Department of Surgery, Hospital of the University of Pennsylvania P JLreudomyxoma peritonei hai been auoci- aled with spectrum of pathologic states varying from benign mucocele of the ap pendix to adenocarcinoma.1 The determina tion of proper management it difficult for many reason,. This condition it teen infre quently, and therefore most surgeons lack extensive previous experience. The degree of malignancy, when prerent, is variable, thus affecting the prognosis. The presence of large quantities of gelatinous material within the peritoneal cavity gives rise to local mechanical complications, especially intestinal obstruction, and also impede, the usefulness of local chemotherapeutic agents. Various agents, such as hyaluronidase and trypsin, have been used in an effort to lique fy the gelatinous material. Denize and Laufman' have demonstrated in vitro dissolution of the mucinous material with the use of trypsin, even though in vivo therapy failed to modify the course of their patient's disCMC. A case of pseudomyxoma peritonei sec ondary to mucinous adenocarcinoma of the appendix it here presented with the results of in vitro attempts to liquefy the gelatinous materia] found in the patient's peritoneal cavity. CASE REPORT A 33-year-old man hsd an emergency ap pendectomy at another hospital 18 months prior Received (or puUkalio* July 1469. "Advanced Clinical Fellow, American Caoccr Society, ""Clinical Fellow, American Cancer Swirl)*. VM, tiH, No. 2, pp. .'101-303 to hit admission to the Hospital of the University of Pennsylvania. The diagnosis at that time was perforated adenocarcinoma of the appendix, and much gelatinous material was noted to be present in the peritoneal cavity. He was again hospital ized elsewhere two months prior to his admission to this hospital because of a one-year history of increasing obstipation, tenesmus, and bloodi streaked stools. An exploratory laparotomy re vealed much gelatinous material covering mul tiple tumor implants, the largest of which In volved the rectum; a left transverse loop colos tomy was performed. The patient was referred to this hospital for possible further therapy. Positive physical findings upon admission to our hospital were restricted to the abdomen. A functioning left transverse colostomy was noted. The patient's umbilicus was Involved with tumor from which gelatinous material oould be ex pressed. No organomegaly was found and there were normal bowel sounds. Rectal examination revealed a tumor-laden Blunter*) shelf compressing the tectum posteriorly in such a way that digi tal examination was restricted. The patient also had back pain involving the area of the lumbar pine and sacroiliac joints bilaterally; but no tenderness was found. Admission laboratory studies revealed a hemo globin of 11.5 Gm. percent. White blood ceB count, fatting blood sugar, blood urea nitrogen, serum electrolytes, serum bilirubin, serum alkaline phosphatase, and bromsulphalein retention were ell within normal, limits. X-rays of his chest, lumbar spine, and an intravenous pyelogram were free of disease and revealed no evidence of metastasis. Barium enema revealed an extrinsic . pressure defect displacing the rectum posteriorly and a filling defect at the splenic flexure of the colon. A liver scan revealed a possible intrahepatic metastatic lesion involving the left lobe. Examination with a pediatric proctoscope re vealed a hard white tumor starting at 4 cm. that almost completely encircled the rectum. Biopsy revealed mucin-producing adenocarcinoma. Ass August, 1970 SURGERY 301