Document VG9wERQ0qGReYppDp9dQ221wZ

Extra- and Intrahepatic Portal Hypertension without Cirrhosis (Hepatoportal Sclerosis) * William P. Mikkelsex, M.D., Hvgh A. Edmondson, M.D., Robert L. Peters, M.D., Allan G. Redeker, M.D., Telfer B. Reynolds, M.D. From the Departments of Surgesy, Medicine and Pathology, University of Southern California School of Medicine, Los Angeles, California When portal hypertension occurs in the absence of cirrhosis, extrahepatic portal ve nous bed block is most often indicated etiologically. Ablation of blood flow through the portal vein is believed to be the domi nant pathologic mechanism, while liver architecture and function remain undis turbed. Cases of unexplained portal hypertension have been reported in which hepatic archi tecture and function were considered to be normal and in which the portal vein was patent-*-r- * '* - ^ " Information con cerning the later assessment of these cases is conspicuously lacking. Occasionally we have also observed cases of this type. Many were considered to be examples of extrahepatic portal hypertension until portal vein patency was established by splenoportal venography, operation or both. When a more critical inquiry was directed toward this group, curious features were identified. Although the usual mode of initial presen tation was unheralded varical bleeding; oc casionally it was ascites. Whereas function and gross and histologic appearance of the liver could be interpreted as being within normal limits on initial presentation, and whereas most of the patients appeared clinically well after operation, none of these features was necessarily sustained. Most pa- 'Presented before the American Surgical As sociation, May 13-14, 1965, Philadelphia, Pa. Aided by X1H Crants HE-01718 and AX0580104. tients later developed abnormal liver tests, some became encephalopathic and a few subsequently died in liver failure. Enigmat ically and surprisingly, all of these curious features were duplicated in the patients with classic extrahepatic portal hyperten sion who were seen during the same period. Patency or occlusion of the portal vein seemed to be the only distinguishing fea ture. Further in none of these adult cases of extrahepatic portal bed block could a specific causative mechanism for the portal occlusion be identified; specifically, none had sustained any of the processes pur ported to be etiologic such as omphalitis, peritonitis, pancreatitis, polycythemia or abdominal trauma. In addition, a few pa tients possibly representing an intermediate stage or a bridge between the two groups have been observed in whom the portal vein was incompletely obliterated by a sclerotic process. In other respects these patients were indistinguishable from the others. Clinical and pathologic details of these three groups of patients are being presented not only because of the clinical interest they evoke, but because of a grow ing suspicion that they may be variants of the same underlying disease mechanism. We suspect that this underlying mechanism may reside within the portal vein and venules, and have chosen the term hepato portal sclerosis to describe this disease process. 602 24924001 UMI Article Clearinghouse has reproduced this material with permission of the copyright owner. Further reproduction is prohibited. BFG36398  *M umbtr * HEPATOPORTAL SCLEROSIS Material This study includes 36 adult patients with portal hypertension whose livers were initially considered to be functionally and architecturally within normal limits. They were selected from patients operated upon for portal hypertension during the last IS years at the Los Angeles County Hospital and from the private practice of the au thors. They have been separated into three groups fur the purpose only of initial com parison. Croup 1 (13 patients) represent those with extrabepatic portal vein occlu sion. Croup 11 (6 patients) represent those with sclerotic, incomplete obliteration of the portal vein. Croup 111 (17 patients) are those whose portal vein was widely patent. The status of the portal vein was estab lished in all patients by means of splenoportal venography, operation or necropsy. Many of the patients in Croup III, those with an open portal vein, were obtained by reviewing the wedge biopsies of the liver in all patients who had had a porta caval shunt Some of these patients who had a suspiciously normal appearing biopsy were excluded if the size of the hiopsv specimen was insufficient to preclude the possibility that it might have represented only a segment from within a large hepatic nodule. Similar cases with noncirrhotic ap pearing biopsies were excluded if the op erating surgeon described the gross ap pearance of the liver as being nodular. Three patients with segmental splenic vein occlusion due to chronic pancreatitis were also excluded since their established etiol ogy and marked difference in management requirements separate them from all other cases of portal hypertension. In Table 1 the gross clinical data are summarized and in Table 2 a more de tailed, individual compilation is provided on the 36 patients. The mean age was 43 years with a range from 17 to 74. Distribu tion by sex was nearly equal. Chronic alco holism was present in only two of the entire group, Cases 3 and 15. Two thirds are cur rently alive, one to 18 years after initial presentation. Of 12 deaths, seven were due to hepatic failure, three to exsanguination and two were postoperative fatalities. Ap proximately one third developed ascites and an equal number subsequently became encephalopathic. There was no important correlation between the initial presence of ascites and the subsequent development of encephalopathy; only four of those with ascites later became encephalopathic. The degree of ascites was variable. In two. Cases 10 and 36, moderate ascites was present only at necropsy. In six. Cases 5, 9, 14, 24, 32 and 35, tense ascites occurred at some time prior to operation. In the re mainder, ascites of 500 to 1,000 ml. was noted at operation. With the exception of the two patients in whom terminal ascites occurred, only three patients had persistent postoperative ascites. All three were mem bers of Croup I (extrahepatic portal hyper tension) and in none was portal hyperten sion relieved by the surgical procedure. Two of these. Cases 5 and 9, are dead. The third. Case 1, currently has only minimal Tuie 1. fjri- ami futrakefratie PortaJ Hyptrltushm Cirrhosis Summary nf Cltuhol Data Total Group 1 Group 11 Xuntcr of cases ,\ge--mean inasr) Sn--nair/iroale Asdics fjccpblopatbr Deaths (bipiic failure) 36 43 (17-74) 17, to 13 12 12 (7) 13 Ax (17-73) 6/7 5 3 4 (2) 6 47 (30-74) 4/2 2 0 1 Sdfrosiii. Group III 17 52 (29-71) 7, in 6 9 7 (?) 20 * CO 20 * O 8 BFG36399 Q 4 00t9Od9 24924003 u.wq scq Aqirdnjcqda.iua `japujrui.w aip U] 'uopiuodo puioos 04) a.vt.uns <>) p.qnq juajind sjqj_ *.<)uaA.>s sjj qju.-> oj jjojjo uc uj uoisupv.1 oiuojoa a.uiKJodo o) junqs jcaco -cpod jojjc sjcaa po[ puc Suijcjpcdcau; pur OJtOAAS SCA\ AI[lcdO|CqdV>Ud *g 3SGQ uj uopnjodo Jojjr sjcoA Oinjicj aijcdaq oj anp qu-'P acj paicuiuuo) sc.w Xjjcug puc `aAissjjSojd }nq `juajjimjaiut sew Aipcdoj cqdaaua `c-j: oscq uj -Sujpwjq jcupsa) -U|OJ}Scg qjtw uoijci.vissc u; sc.w ]l c OSC3 UJ puc `AJUO A|(CUIUUa) [WMJKMO 1! *J puc j-j *53 `g `c sasij `sjuaqnd oaij uj vqqcucA osjc sca\ AqjcdujcqdJJUJ jn aajSap aqj, snjcis sup uicjujrui oj Xicsso-wu si uiciSojd opajinp jvmupuo.1 c jnq Sajpsc qn. 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S113H.L0 cixv xanaxMiiv too >w HEPATOPORTAL SCLEROSIS 605 vith Portal [iyptrlmion vilkuiU Cirrhosis 0|ndui A** Tyi* List Awcnamt nSihBia- thrPormo-- BSaPt Ate sa (Gm.r;> ti> min.) > Comment* Gmn'p I. Fortil Vein TotmUy Ckdnded 44*47 E*. MS 4J is 1a9 tr SS.*Cl-M s, xx 44 3.9 X* 49 14) 3.8. 5-0 20 -- -- 20 -- 4_2 XI U $9 -- -- Alive; a*ctte*; one minor hemorrhagr: notnctphalepathy. 2--5 AAlliivvee;*prweseullm; naoblbylewerdOin;gn,ombnMphinaltoinihj or write*. to 10 Dead; exsangntnation. 42 3S to 44 S.sE,xX, XT. KG 64 51 XI 0.4 31.XI A7, 4j4 5900 Dead; hepatic failure aad hemorrhage. 13 Alpivreo;blenmo.bleeding. ascites or encephalopathy. Nutritional -- 61 -- 31 4j6 -- 14 Alive; one hemorrhage; no ascites or encephalopathy. 232*037 SSR, KG 2351 0--,7 3JX1 XJ 4.4 IIwS 143** ADleivaed;*hewpealtli;cnfoaiWlureeedainndg.iennarnerptimhavlofwthy or write*. 5tfcS9 41 to 43 EsS.C.Tl-M.Tr 62 44 OLt IJ UXI.341.9 19 -- Dead; euwHgutnation; had write*. 60 43 Afive * writ; oo bleeding. encephalopathy orasrite*. 73 17 SR SR 75 20 OLt 3X49.XX24 4754 391* AMlilvwe;4penreiolld'iicfxenc;epwhvabl1o--pathy; axobriitndinrgwowrapslc.^iteUsp. tl.y 40 54 3*1 56 61 3*57 PC* PC S. PC PC PC SR Caocp II. fnrfl Vein PnrtUBj OtetwUd 40 _ -- 33 0.7 -- 59 -- 31 DAelivaed o*newmelol:.fpeotodr-;onpo.;eenmcneBphgaaltoupaatitohay:, PblCeesdhinngutoorewdraidtee*d.. U U 3A. XO u 1.9 30U ftl -- U 15 47 1 JJ. X9 53 --35 15 2152* Alive; severe Pukbwn'i; no bleeding or ascites. Afire * well; no encephalopathy, bleeding or write*. Alive * well; no encephalopathy, bbufing. writes. 6t 20 Afire * vdl; no ncnthalopatly, bMing,txitea. Gkocp 111. Portal Vein Patent 47 PC 71 PC 61 PC 44 54 PPCC 53 363aSnd 49 PC SK S. PC 50 PC _ 66 59 PPCC 47 PC 5516 SR S 6740 PC PC 65 1.4 4-1 X9 75 63 59 4--_.4 3i 37 -- -- 54 54 ---- -- -- 44 04 4.S.A4 51 5249 69 11_..14 -- U3S X4--.X1 --' 64 1.9 34/13 51 X4 12/73 59 1Jk U3I 57 44 0--7 30/4.4 -- 72 1.4 2J. AO 44 29 Alive; encephalopathy IS year* Mm; no bhedfitf. write*. 50 22 Alive; mild enrephalotwthy; fetor; no bleeding or write*. ----. -- Dead; hefntic failure. -- Afive; Parkin**'*; no encephalopathy or bleeding. -- -- Dead; ketotic failore. --. -- Dead; rme mce}4olo|otby; hepatic failure. 75 23 Alive; not recently examined. ISO IS Afive * nefl; fetor; no bfcediug. encephalopathy of write*. 54 J--O. Afive; m9d enceiJudopothy; oo bleedingor write*. Dead: esmagaiaatioo; also had lomen*looephriti*. -- Alive * well; noencephalopathy, uritci 31 34 Afive; tadd encephalopathy; fetcr; no bkcdiag or write*. to3o1 -- Dead; hepatic failure. 42 Alive * writ; no encephaloputhy. binding or write*. 42 -- Alive; fetor; mild encephalopathy; aoascites or bfcuHng. <-- -- Dead; postoperative pemoniti*. It 34 Dead; postop. colon eariadon; tewe encephalopathy. No bleeding. intermittent and generally either easily con trolled or self limiting. All of these had had a portacaval shunt and were members of Croup III, except Case 12 who was in Group I and had a splenorenal shunt. One patient. Case 20, did not become encephalopathic until 15 years after his portacaval shunt. Periods of lethargy and confusion lasting about 3 dux's at a time hax-e con tinued in this patient over the last 3 years. The ages of those who developed periodic encephalopathy ranged from 47 to 73 years with a mean of 60 years, an age greater than the mean for the group as a whole. Minimal hepatomegaly xvas often de tected. However, hepatomegaly of greater than one fingerbrradth extension below the costal margin was noted in only four pa tients, and in three of these the enlargement was but two fingerbreadths. In contrast, splenomegaly was usually present and the degree of splenic enlargement seemed greater than that usually presented with cirrhosis. Portal pressure recorded at op- 24924004 (mc. 1. Case 5. The operative liver biopsy. (Lift) Low power showing widening of the portal areas anil dilation of at least one hepatic vein. Nodular regeneration and septal fibrosis are not seen. (Right) High power of portal area which shows several thin-walled vascular spaces and two arteriolar radicals. The limiting plate is intact. oration was nt>t different, on the average, from other types of portal hypertension. Leukopenia and thrombocytopenia ap peared to be more frequent and more severe than that usually assoeiated with cir rhosis. The four patients in Croup III in whom an epigastric venous bruit was pres ent could probably he classified as typical examples of Cruveilhier-Baumgarten dis ease.5 However, a patent umbilical venous connection to the left portal branch was not proved in any of them. As will be noted in Table 2. hemixlynamic studies as represented by wedged hepatic vein pressure (WI1VP) and he patic blood flow (HBF) were determined in only a few patients, anil most of these were in Croup I. The WHYP in two pa tients, Cases 9 and 16. was measured in other hospitals: the values reported were 21 cm. of saline and "elevated," respec tively. In neither was the wedged position verified by contrast material injection; their validity may be questioned. In the remaining 12 cases studied, hepatic vein catheterization was carried out hv one of the authors. In all but one patient the WHYP was within accepted normal limits, in the one exception. Case 6, it was mod erately elevated to 15 mm. Hg. HBF, with the exception of a normal value in Case 2, was consistently below mean normal limits. In a single patient (Case S) it was markedly reduced. Selected Illustrative Cases Case 5. A 62-ycar-old white woman, a chronic alcoholic, provided a history of Four episodes of gastrointestinal bleeding over the preceeiling 6 years. Two months earlier marked ascites had oc curred and paracentesis yielded "two gallons of fluid." Ksamiiiation disclosed a liver palpable two fiiigerbrearlths and a spleen palpable three fingerbreadths Irelow the costal margin. There was mild 24924005 BFG36402 ro< Volume 162 Xumbcr 4 HEPATOPORTAL SCLEROSIS 607 ascites. So stigmata of cirrhosis were evident. Laboratory data were: serum bilirubin normal, serum albumin 4D and serum globulin 1.7 Cm./ 100 mL (Howe method), prothrombin 123%, and bronrsulfalein retention 10% in 30 minutes (5 mg./ICg.). On hepatic vein catheterization the WHVP was normal; HBF was not measured. Varices were demonstrated by x-ray examination. At operation the hver appeared normal, the spleen was markedly enlarged and there were about 200 mL of ascitic fluid. Portal venography with contrast material injected into both the spleen and a superior mesenteric venous radical demon strated occlusion of all of the major portal venous tributaries including the portal vein. Portal pres sure was measured as 36 and 47 cm. saline in two collateral veins. Splenectomy and transesophageal ligation of varices were performed. Microscopic examination of the operative liver biopsy showed widened porta] areas containing dilated, thin-walled vascular spaces (Fig. 1). Central veins were dilated and appeared increased in number when related to the number of portal areas. Nodular regeneration and septal fibrosis were absent. Histologically the spleen demon strated dilated sinusoids with minimally thickened sinusoidal walls. Hemosiderin was absent and endo thelial proliferation was not significant. Scattered Malpighian structures had prominent germinal centers without fibroadenie. During die following 4 years, varical bleeding recurred on three occasions. Mild to moderate . ascites persisted. On her last admission for a rather minor hemorrhage, moderate encephalopathy progressed to deep coma. Within a few days she recovered from com and became alert. One week later, encephalopathy recurred and she died a few days later in hepatic coma. There had been no recurrence of hemorrhage with the second and terminal episode of encephalopathy. Laboratory data on the final admission were: scrum bilirubin 2.1 mg./100 ml., scram albumin 3.8 and scram globulin 3-3 Cnu/lOO mL and prothrombin 50%. At necropsy die body was well developed and nourished and anicteric. There were 1,500 ml. of straw-colored ascitic fluid. The liver was firm and shrunken with an accentuated lobular pattern and weighed 1,023 Cm. There were no regenerative nodules; the surface was smooth. The portal vein within the liver and for 3 cm. proximal to the porta hepatis was patent. Proximal to this site the portal, splenic and superior mesenteric veins were selenitic, totally occluded and hardly Identifiable. There were several, small, thin-wailed vascular structures around the sclerotic area. The esophagus had tortuous, dilated submucosal veins. There was a 2.0 by 0.4 cm. ulcer in the second portion of the duodenum. Bloody fluid was present in the stom ach and colon. Histologically the liver showed a striking change from that observed four years before ( Fig. 2). There was an extensive arachnoid pattern of fibrosis extending from portal areas which de stroyed the limiting plates and often connected adjacent portal areas. Clumps of liver cells ap peared entrapped by the fibrous process, but there were no regenerative nodules. Bile stasis was prominent in the centrolobular canaliculi and there was some eholangiolar proliferation. Some of the interlobular ducts had periductal lamellar fibrosis. The prominent portal arterioles and angiomatous spaces observed 4 years previously were no longer apparent. Case 36. A 70-year-old white man was ad mitted for his first and only major gastrointestinal hemorrhage. There was nothing of significance ob tained from his past history and he was not alco holic. Examination disclosed splenomegaly as the only positive finding. There were no stigmata of cirrhosis and the liver was not palpable. Labora tory data were: serum bilirubin 0.5 mg./100 mL, serum albumin 4.7 and serum globulin 2.8 Cm./ 100 mb, prothrombin 60% and bromsulfalein re tention 10% in 30 minutes (3 rog./Kg.). Large varices were demonstrated by x-ray and rsophagoscopy. Massive intraperitonea) hemorrhage follow ing an attempted and unsuccessful percutaneous splenoportogram necessitated emergency operation and additional hemodynamic studies were obvi ated. At operation the liver was normal in gross ap pearance and the portal vein was enlarged, tense and patent There was a large amount of intra. peritoneal blood which arose from a 2-cnt. lacera tion of the spleen. The laceration was temporarily tamponaded and an end to side portacaval shunt was done. Portal pressure was reduced bom 40 to 15 cm. saline. Bleeding from the splenic laceration had ceased after completion of the shunt so the spleen was not removed. Microscopic examination of the operative liver biopsy disclosed neither nodularity nor increased fibrosis (Fig. 3 A). The central vein radicals were increased in number and some were quite dilated. Some ported areas were enlarged ami contained thickened arterioles and slightly dilated venous structures. Some of the parenchymal cells scented slightly swollen. The appearance of the biopsy as a whole could readily he classed as nonnaL For the first 2 days pustoperatively, the pa tient was comatose. Subsequently his early post operative course was uneventful. Hepatic vein catheterization done a few months after operation Bp036403 60S MIKKELhKN AND OTHERS Anna)* >4 >urcrrv Iklober lVt>5 Fio. 2. Gvse 5. Necropsy se. tions 4 years after operation. A. (Left) Low power of liver slam-inn ex tensive arachnoid fibrosis willi ilestmction of the limiting plate of the portal areas but without ixxlular regeneration. The previously noted angiomatous change is no longer present. B. ( Bight) A major portal area with extensive fibrosis. In the venter of the field is a portal vein radieal with lamellar fibrosis or sclerosis. Fic. 2C. Sec tion of cvlraliepatic portion of the portil vein showing disruption of muscular layer try fibrosis and market) xulrendothelial sclerosis. disclosed a W11VI* which was slightly elevated; 11BF was B45 ml. per minute. Not long after operation, periodic encepha lopathy developed. This complication progressist until its degree Ix-came incapacitating. Hoping to reduce its severity, operative, colonic exclusion was performed 2 years after his portacaval shunt. The patient failed to sun ive this operation and died on the ninth postoperative day in hepatic failure. There had been no recurrence of varii-al bleeding. laboratory data obtained just prior to the second operation was: serum bilirubin 1.4 mg./100 inL serum allxnnin 2.3 and scrum globu lin *3.0 (ao./lOO ml., prothrombin 4Sri and brom- sulf.dcin retention rfi^i in 30 minutes (5 mg.; Kg.). At necropsy the IkhIv was anicteric. wi ll de veloped ami well nourishisl. There were approxi mately 150 ml. of opaque, fold ascitic lluid. A fibrinous exudate covered a small perforation at the site of the iliosigmnidostomy. The liver, weighing JfiX) Can., was greatly reduced in si/e, rublicry ami firm. The parenchyma was mottled with an accentuated lolxdar pattern hut without nodularity. The biliary tract was normal. The portacaval anastomosis was patent. The spfccnvV weighed 5T0 (tin. and was soft without prnminenthU architectural markings. CO Microscopicallv the liver showed a striking o Volume lb* Number * 11 Hl'ATOPO KTA1. SCLKHOSIS raj! HS&i S*t! ISM 609 Ml Fig. 3. Case >6. (Lift! Low ;V)Mit of opcrutive liver biopsy showing the absence of significant fibrosis and the close approximation of porta) amt central vein ureas, in the center is a prominent cen tral vein. Some lixer cells appear swollen, (flight) bow power of necropsy Motion of liter 2 years after operation which shows extensive fibrosis spreading from portal areas with disruption of the limiting plate. crease in fibrosis with arachnoid collagenous fiUrs extending from the porta! areas in a haphazard fashion (Fig. > B>. Nodular regeneration was absent. In some of the scarified portal regions there were increased immlnrs of lyinphoo tc> and tholangiolcs. Tfe x.iwulur elements were no longer accentuated a< they hail tccn in the biopsy spiimeii *2 years previously. The spleen demonstrated mildly diUttd dmisoids with proliferation of die lining tells, ImiI their walls were not unusually thickened and there was no deposition of henm-_ sidrrin. Lvmplioid tissue was atrophic. In some areas there was a nodular configuration of the sinusoids approximating the size of Malpighian corpusclt*s lut not demonstrating jh iik illiaiy ar teries. Case 26. V .Vi-vruf-oM while umimi. ii"ii* alcoholic, had her first gastrointestinal lirnionhag** 2 years prexhmdy atnl her second on this hospital admission. 'Hiere were no other significant details in her past history*. Ksummation disclosed splenomegaly as the only positive finding, lliere were no stigmata of cirrhosis and no ascites. Luliorutory data Were: M-nun hilinihitf 0.5 mg./100 mb. serum alUimin 3.c) ami M-mm gtohufin 3.S Cm. '100 ml., pri>- thromhin 7urJ and hromsulfulein retention less than U)rr in 30 minutes (5 mg.. KCg.L Large varices were demonstrable on way am! esophagus- ipx\__On liepatie v in cathrteri/uthni thx* WltVI* wa*. norma); 1IUF was net ifftt riuiiiel. At operation the liver appeared normal while the spleen was greatly enlarged l Fig. -1 Ab There vv.is no um ites. Operative sptcHopoiLd venography ih-snou\tratd patency of the portal vein (fig. I It'. 1 he |Hital vein Wav divsrvtcd free sutfi- lirndy to permit taking x vlifev t portal pressure wliiih was ini. saline. A splclievtomy and spl iioreii.il shunt were done. Tost shunt pressure was l") i m. saline. Mu rowopic examination of the liver biopsy disi hned no evidence of septal fibrosis or nodular re- BFG36405 "*3 V 0 L 610 MIKKELSEN AND OTHERS Annals of Surgery October 1965 Fic. 4. Case 26 (Left) Operative photograph which shows an essentially normal appearing liver anJ a markedly enlarged spleen. (Right) Operative splenoportal venogram which shows a patent portal vein and coronary' vein collateral. generation. The hepatic veins were disproportion ately numerous and appeared dilated (Fig. 5 A). Many of the portal structures were dinninitively small, others were enlarged with diluted vascular spaces and with marked perivascular and peri ductal fibrosis (Fig. 5 B). The spleen weighed ThO Cm. Microscopically it showed dilated sinus oids with thickened walls. Only slight endothelial proliferation and very little fibrosis existed. There were no germinal centers and the lymphoid struc tures did not present adenomatous vascular trans formation. Six months later mesenteric venous occlusion necessitated the resection of 6 feet of small bowel. Six years have elapsed since operation and while the patient is known to l>e alive and to be presum ably well, she refuses to return for evaluation. Her last clinic visit was three years after operation at 24924009 Fic:. 5. Case 26. Tire operative liver biopsy. (Loft) Low pow*er showing multiple dilated hepatic out flow tracts in close- approximation. Septal fibrosis and nodularity are not present. < Right) High power of an enlarged portal area with increased numbers of vascular channels and periductal fibrosis. Note the eccentric sclerosis in the largest portal vein radical in the center of the field. BpG36406 ro 4uim 162 amber 4 HEPATOPORTAL SCLEROSIS 611 'h time she was clinically well without enialopathy, ascites or recurrence' of varical feeding. Her laboratory data at that time were: rum bilirubin 0.4 mg./100 ml., scrum albumin 5 aryl serum globulin 3.4 Cm./100 ml., proirombin 75%, and bromsulfalein retention 23% l 30 minutes (3 mg./Kg.). Case 17. A 61-year-old man, non-ulcoholic, had iis first gastrointestinal hemorrhage at 38 years of ge and his second on this hospital admission, fhere were no other significant details in his past listorv. Discussion All of tliese patients presented as exam ples of portal hypertension with established varices. All but two bled from esophogogastric varices and in 29 this was the initial manifestation of disease. Clinical features Examination disclosed splenomegaly and mild iscites. The liver was not palpable and there were k> stigmata of cirrhosis. Laboratory data were: emm bilirubin 0.9 mg./lOO nil., serum albumin 13 and serum globulin 2.3 Cm./100 ml., proJirombin 63%, and bromsulfalein retention 7% in 15 minutes (3 mg./Kg.). Varices were demon strated by x-ray examination. At operation the liver was normal in size, color md contour. Its edge was sharp (Fig. 6 A). The nnly gross abnormality was the presence of a fine trabecular network over the liver surface; there was no nodularity. The spleen was significantly enlarged and there were approximately 300 ml. of ascitic fluid present Operative splcnoportal venog raphy demonstrated either the ciTcct of portal streaming or partial occlusion of the portal vein (Fig. 6 B). The latter was proved to exist The partial portal vein occlusion was due to a very adherent sclerotic process that extended from the ta hepatis to the origin of the portal vein and .iuded the vein by about 60% (Fig. 6 C). A cleavage plane existed and it was removed cleanly, leasing a smooth appearing intimal surface. Endto-side portacaval shunt was done which reduced portal pressure from 47 to 20 cm. saline. Microscopic examination of the liver biopsy showed an almost normal architectural arrange ment The central veins were unusually prominent. Many portal areas were enlarged and contained thickened vessels. Histologically the material ex cised front the extrahepatic portal vein (Fig. 7 A) demonstrated a collagenous pattern with an in tact and smooth endothelial lining. Its appearance was not unlike that of the phlebosck-rotic process within the portal areas of the liver (Fig. 7 B). Postoperatively he has remained well. There is no encephalopathy or ascites and there has been no further bleeding during the 27 months since operation. His current laboratory data are: scram bilirubin 1.9 mg./100 nil., scrum albumin 3.0 and scrum globulin 2.5~tjm!'/fb0 "mt^ prothrombin 33%, and bromsulfalein retention 12% in 45 min ute* (5 mg./Kg.). Fie. 6. Case 17. (Ton) Operative photograph which shows the sharp edge of the essentially nor mal-appearing liver. The fine trabecular network over the surface of the liver is discrmable. (Center) Tile operative splenoportal venogram showing par tial occlusion of the portal vein. (Bottom 1 The sclerotic material removed from the lumen of the portal vein. nlutnv lb* um!-r 4 BFG36407 HEPATOPORTAL SCLEROSIS 613 nrwr drvrfon cimioli- luted vast'll!.ir spates mid frts|in*ntly more 612 MIKKELSEN AND OTHERS Annals of Surgery October 16S FiCyrT. Case 17. (Left) Cross-section of the sclerotic material, shown in Fie. 6 C, that was excised from the lumen of the portal vein. The material is collagenous without hemosiderin or calcium deposi tion. There is an intact endothelial lining. (Right) Section of a portal area within the liver showing a similar phlebosclerotic process to that seen in the extrahepatic portal vein. or complications of hypersplenism or socalled splenic anemia were not obvious al though leukopenia and thrombocytopenia were present in two thirds of the pa tients. Ascites and encephalopathy, al though somewhat more common in the group with a patent portal vein, were ob served in an appreciable number of those with extrahepatic portal vein occlusion. Others have also noted the occasional as sociation of ascites with extrahepatic portal hypertension.'-3- * *:i The mechanism by which ascites developed in these patients is even more obscure than it is in cirrhosis. One report recently has called attention to the not infrequent occurrence of abnormal liver function tests and encephalopathy in extrahepatic occlusion.55 This report sug gests further that these abnormal liver tests develop in proportion to aging and that such abnormalities arc rarely seen in chil dren. Although not included in this report. we have observed an appreciable number of children with extrahepatic portal hyper tension who had abnormal liver tests and ascites.5' During the years covered by this review, we have operated upon almost -400 patients with portal hypertension. The 36 patients presented here thus account for almost 10 per cent of the whole. It would, however, be incorrect to assume that this disease actually represents 10 per cent of all our cases of portal hypertension. The great ma jority of patients with varical bleeding that we see have cirrhosis associated with alco holism. Most do not survive their hemor rhage to receive operation and many that do survive prove to l>c unreliable and fail to return for surgical therapy. The non alcoholic patients, in contrast, are generally reliable: most survive their hemorrhage and return for follow-up treatment. In ad dition there are a large number of patients kb: BFG36408 v Volume 162 Xumbrr 4 HEPATOPORTAL SCLEROSIS 613 with cirrhosis who never develop compli cations of portal hypertension. The correct incidence of the disease here presented probably is closer to 2 or 3 per cent of our cases with portal hypertension. Pathology luted vascular spaces and frequently more than one arterial branch. Frequently the portal vein radicals were significantly thick ened or sclerotic and occasionally they were differentiated from the arterial branches with difficulty*. Cholangiolar proliferation was notably absent. Morphologically the livers of patients from the three groups (occluded, partially occluded and patent portal vein) were grossly and histologically indistinguishable. At the initial operation, the livers were es sentially normal. The color was a normal red to mahogany-brown; the surface was smooth or occasionally traversed by a fine, lacy, fish-net trabecular pattern. Rarely the surface was mildly irregular, but it was never nodular. The inferior edge was sharp in most, slightly blunted in a few. Although a few were mildly enlarged, the gross con figuration was normal in all. Insariablv there was a slight, but definite, increase in firmness. The liver edge could not be as easily folded back on itself; it was not as supple or flexible as normal. Sutures used to approximate the edges after a wedge biopsy were unlikely to cut through. On the initial liver biopsy, histologic de viations from normal were subtle. There were no fibrous septae or regenerative nodules. Nevertheless the lobular arrange ment was insidiously deranged. There were often several dilated vascular spaces, pre sumably hepatic veins, in a single lobule and many were quite close to the portal regions. Two or three portal areas were closely spaced in one area, yet in another they were widely separated. Scattered ir regularly throughout the parenchyma were portal areas greatly enlarged by the depo sition of perivascular and periductal col lagen. In these areas the limiting plate was intact and the collagen was sharply de lineated fnm parenchymal cells. In smaller portal triads this limiting plate was par tially* disrupted. Within these abnormal portal triads there were usually several di- Tlie material which partially occluded the portal vein in those patients in Croup II was indistinguishable from that respon sible for the complete portal vein oblitera tion of patients in Croup I who were ex amined at necropsy. The thickened mate rial was placed eccentrically and there was a notable absence of hemosiderin, calcium or a lamellar pattern. The material closely* resembled atherosclerotic deposits in ma jor arteries except that it contained no lipid. In the few* patients, subsequently ex amined at necropsy* who died in hepatic failure 2 or more years after initial pres entation, there was a striking change in he patic architecture. The liver was shrunken, firm and somewhat irregular, but it was not nodular. Weight ranged from 700 to 1,000 Cm. Histologically the limiting plates of the portal areas were disrupted by an arachnoid pattern of fibrosis which had the appearance of sweeping through the he patic parenchyma entrapping segments or clumps of liver cells. The dilated and pro liferated vascular spaces, seen originally*, had disappeared. Regenerative nodules were still not apparent. Splenomegaly was a consistent feature and its degree was greater than that usu ally encountered in association with cirrho sis; the spleen weight averaged 67S Cm. for the eight patients in which this infor mation was available, in contrast to an av erage of 309 Cm. for S3 cirrhotic patients examined at necropsy*. Microscopically the sinusoids were diluted and their walls thick ened, but the vascular change of "fibroadonie* described by Banti was not ap parent. Cj5 O 16 4 BFG36409 614 MIKKELSEN AND OTHERS Aaoab of Surgery October 196$ Nature of the Occlusive Process in the Portal Vein For years disagreement has existed con cerning the nature of the portal vein oc clusive process in extrahepatic portal hy pertension. Is this secondary thrombosis or primary phlebosclerosis? Evidence has been marshalled on both sides and it would ap pear that those supporting thrombosis have been most convincing.11'"' "'50' " It is appreciated that the differentiation is diffi cult to make. Nevertheless we have been impressed by certain features and present these in support of this concept of phlebo sclerosis. In some patients in Group III, those with a patent vein, there was eccen tric thickening of the portal vein wall, usu ally on its posterior aspect. Admittedly the portal vein wall is thickened in nearly all instances of portal hypertension regardless of its nature, but this area of eccentric thickening was localized and distinct and was 2 to 4 mm. in depth. It was firmly ad herent to the vein wall and its inner or intimal surface was smooth. It is difficult to conceive that this could be thrombosis; it is not unlike intimal thickening in ar terial atherosclerosis. We are inclined to think that the patients in Group II, those with partial occlusion of the portal vein, represent an extension of this process. In those in whom an endophlebcctomy was done the sclerotic material was very firmly adherent and the plane of dissection was not readily identified. This aspect is strik could be argued that the difference be tween the tw'o was a manifestation only of age; and perhaps this is true. However one final feature merits consideration in this question. In many of the patients from all three groups there was, histologically, dis tinct and impressive concentric thickening of the peripheral portal vein radicals within the liver. This must be sclerosis; its pres ence indicates that an identical process may occur in the extrahepatic portion of the portal vein. If the existence of phlebosclerosis is ac cepted, it is then interesting to speculate whether it has preceded or followed portal hypertension. Intrahepatic, presinusoidal, portal venule resistance as a result of phlebosclerosis conceivably could induce portal hypertension in a manner similar to' schistosomiasis14 or to experimental injec tion of silica particles." Conversely it is perhaps easier to con ceive of phlebosclerosis developing as a secondary process, that is, developing in response to portal stasis and hypertension." This hypothesis, however, is not supported by the venous findings in the far more com mon form of portal hypertension due to cirrhosis. In cirrhosis, symmetrical thicken ing of the extrahepatic portal vein w'all occurs, but we have not seen eccentric phlebosclerosis (or thickening). Also if phlebosclerosis is a secondary phenomenon we are left with no explanation for the pre sumed intrahepatic vascular block. ingly different from those patients with cirrhosis who have obvious thrombosis within the portal vein. Five or six patients with this latter process have had throm bectomy and subsequent portacaval shunt performed. In all the thrombectomy was accomplished with surprising ease; the plane of dissection was immediately identi fied, adhcrance to portal vein w'all was much less intense and histologically there was no doubt that the removed material represented an organized thrombus. It Unquestionably there exist other types of portal vein obstruction which lead to portal hypertension. A localized stricture or area of portal vein stenosis probably on a congenial basis has been reported.*- " Congenital stenosis of the entire portal vein has been encountered; ** and perhaps its congenital absence has occurred. Al though compression from without the por tal vein due to neoplasia has been re-^> ported" we have not seen such a lesion^ which induced varical bleeding. All of thefj^i BFG36410 O h* CO Volumt 162 Number 4 HEPATOPORTAL SCLEROSIS 615 above mechanisms are undoubtedly un usual causes of portal hypertension. Mechanism of Portal Hypertension As implied before, the hemodynamic al terations responsible for portal hyperten sion in these patients remain obscure. For one reason or another we have been re peatedly thwarted in obtaining complete hemodynamic data in our patients in Croup III, those with a patent portal vein. Wedged hepatic vein pressure was normal in the three such patients catheterized and he patic blood flow was reduced in the two patients in whom it was measured. A large experience with an apparently similar dis ease has been bad by the Nagoya group in Japan.1* In their patients WHVP and HBF were not elevated. These data are identical to those obtained in Croup I patients, those with extrahepatic portal hypertension. It is difficult to accept the hypothesis of in creased splanchnic arterial inflow- as the sole mechanism responsible for the portal hypertension in those patients with an open portal vein. If this were the case, hepatic blood flow and cardiac output should be greatly increased.3 Arteriovenous shunting as a cause encounters the same theoretical argument.11' '*3 Although not apparent histologically, it is difficult to escape the belief that vascular obstruction within the liver must exist. This obstructive mecha nism for elevation of portal pressure is in greater consonance with the currently available hemodynamic data. If the eleva tion of WHVP which is usually seen in cirrhosis correctly implicates a sinusoidal or postsinusoidal location of hepatic vascu lar block,3 then the block in the cases un der current consideration should be presinusoidal. Normal WHVP has been re ported with portal hypertension in a num ber of different liver diseases, so that it would be wrong to place a patient in the category that we are describing on the ba sis of this finding alone. Semantic Considerations Are some of these patients representative of those studied by Banti? Those most sus pect for such a designation would be the few who died later in hepatic failure and in whom necropsy disclosed a shrunken, - firm, fibrotic liver. If this be the case then it must be assumed that Banti was liberal in his use of the label cirrhosis. This error is understandable; it was not too long ago that "international criteria" were estab lished for the pathologic designation of cirrhosis. Today many pathologists would label our few late cases with extensive fibrosis as cirrhosis. However none demon strated regenerative nodules and by the criteria of today they were not cirrhotic. Though on an historic basis, Bantfs syn drome might be an acceptable description, we are reluctant to recommend the rein- trodnetion of a term which has been re sponsible for so much confusion in the past. While in recent years we have used this label among ourselves, it is probably pref erable to let the sleeping Banti lie. It would be pleasing to have a short de scriptive label for this disease which would fulfill semantic requirements, rather than- to employ an unwieldy group of words which describe a negative aspect as in the title of this article. Hcpatoportal sclerosis would fulfill this role as well as any term when related to our current knowledge of this process. Sclerosis signifies firmness or hardness; the portal areas within the liver and the portal vein outside the liver are those afflicted by sclerosis. _ On the other hand it is somewhat pre sumptuous to attempt to label a-disease about which so little is understood. For that matter, is but a single disease entity represented by these 38 patients? We only suspect and have been intrigued bv the possibility that this may be the case. In blind exercise we have never been able to separate histologically the three groups. Additionally there is little to clinically dif- 24924014 Fic. 8. Case 34. The operative splcnoportal venogram which on "second look" demonstrates a widely patent portal vein. It had been previously overlooked because of its lack of contrast and be cause of being partially obscured by a huge, tortu ous collateral. Fic. 9. Case 19. The operative splcnoportal venogram which demonstrates almost complete occlusion of about the mid-point of the portal vein. Formerly classified as an example of extra- hepatic portal hypertension, it now is placed in Croup II, those patients with partial portal vein occlusion. ferentiatc them; mean age is not too di vergent and age range is essentially the same; incidence of ascites and encephalo pathy is similar; initial and later liver func tion tests are identical; and about an equal percentage have died in hepatic failure. Further evidence for this similarity may be marshalled. Cases 16 and 27 had splen ectomy performed elsewhere; their post operative diagnosis was extrahepatic por tal hypertension. Both were later proved to have a patent portal vein. Case 34 is especially noteworthy. At operation the liver was grossly normal and a hard, rod shaped structure believed to be a throm bosed portal vein was presumably palpated in the hepatoduodenal ligament. These fea tures, plus what must have been but a perfunctory glance at the wet x-ray film of the operative splenoportogram, led to a diagnosis of extrahepatic portal hyperten sion which was continued for 3 years until the current review prompted a "second look" at the splenoportogram. The portal vein was unquestionably widely patent but was partially obscured by a huge, tortuous collateral (Fig. S). Case 19 has l>cen used for 10 years in student teachings as an ex ample of extrahepatic portal hypertension. Perhaps he should continue to be so classi fied, but in this study we felt compelled to place him in Group II (Fig. 9). Of addi tional interest is that periodically during these 10 years his liver tests have been more abnormal during three episodes of small bowel adhesive obstruction than those listed in Table 2 which are current. These laboratory results were puzzling since we thought during these years that liver function in portal occlusion remained normal. Case 5, although alcoholic and with documented previous tense ascites, clearly proved to l>e an example of extra hepatic portal bed block with what would Imj accepted as a normal liver on initial presentation to ns. Four years later when necropsy followed death due primarily to hepatic failure, the portal vein within the liver anil for 3 cm. proximal to the porta hepatis was patent. Proximal to this site ^ 4-* o Volume 162 Number 4 HEPATOPORTAL SCLEROSIS 617 the portal, splenic and superior mesenteric veins were sclerotic and totally occluded. Six years before" we first saw her and 10 years prior to death, she had her first gas trointestinal hemorrhage, presumably (but not proved) from esophagogastric varices. Can it be assumed reliably that her portal vein was occluded at that time? And finally what was the status of the portal vein in Cases 3, 6, 9 and 10 at their initial sple nectomy? Because the portal vein was ol>Iiterated at the time they presented them selves to us does not prove that it was so lx-fnrc their splenectomy. Splenectomy alone, in cases of portal hypertension, no toriously provokes splenic and portal vein occlusion and this sequence could conceiv ably be accentuated if some degree of por tal and splenic phlebosclerosis was co existent. In his last contribution in 1910, Banti de scribed 50 patients personally observed." "The characteristic lesions are in the spleen, liver, and almost always in the splenic vein and-portal vein." He called the venous of the intrahepatic and extrahepatic portal vein and venules. The gross and microscopic hepatic mor phology and the clinical features and course were essentially the same for all of the patients. About one third had ascites and an equal number became encephalopathic. Liver function tests, which were essentially normal early, became abnormal later. If recurrent varical henuirrhage was eliminated, most patients in all three groups appeared clinically well. A few in each group, however, did not follow this course and had a steady deterioration in liver function. Seven of the 12 who are dead, died in hepatic failure. In those in whom necropsy was performed, a marked extension of the initial pathologic process in the . liver was noted. It was grossly shrunken and firm but not nodular; micro scopically there was extensive, arachnoid fibrosis which had replaced much of the parenchyma. lesion "chronic sclerotic endopldebitis." When related to the patients presented here by us, it seems strange that Banti did not describe a single case of complete por tal or splenic vein occlusion. Summary and Conclusions Thirty-six adult patients with portal hy pertension, but without cirrhosis, have been analyzed. One third had classic extrahepatic portal hypertension with total occlusion of the portal vein. A few had partial occlusion of the portal win and one half had a widely patent portal vein. Al though the liver has lxrn considered to lx? normal in extrahepatic portal hypertension, we Irelfcve that a distinct histologic lesion exists. Furthermore this same lesion is identifiable in those patients with a par tially occluded or a widely patent portal vein. We suspect that all three types have the same underlying etiologic mechanism and that this mechanism is phlebosclerosis Acknowledgment Our appreciation is expressed to Dr. Arthur C. Pattison who kindly permitted the inclusion, of four of his private patients in this study. References 1. Arcari, F. A. and H. B. Lynn: Bleeding Eso phageal Varices in Children. Surg. Gynec. & Obstet, 112:101. 1961. 2. Armstrong. E. L-. W. L Adams. L. J. Trager man and E. W. Tomsrod: The CruveiihierBaumearten Svndraane. Ann. Intern. Med., 16:113,1912. 3. Raggenstoss, A. II. and E. E. WaRacgcr: Por tal Hvprrtcnsion the to Chronic Occlusion of the Extrahepatic Portion of the Portal-- Vein: Its Relation to Ascites. Amor. J. Med., 21:16. 1936. 4. Britton. R. C.: Discussion of llallcnhcck, O. A. anti M. A. Adson: Esophagogastric Varices without ilrpatic Cirrhosis. Arch. Surg., 83:56. 1961. 3. Clatworthv, 11. 'V. ami E. T. Boles, Ir.: Extrahepatic Portal Bed Block in Children: Pathogenesis and Treatment. Ann. Sunj.. 130:371. 1939. 6. Conley, C. !_ and B. C. Laiconi: The Eti ology of Bunti's Syndrome; Further Support of the "Congestive Splenomegaly' Hypothe sis. Ann. Intern. MerL, 27:2S9, 1947. 24924016 618 MIKKELSEX AND OTHERS Annls of Swaps October IMS 7. Garrett, N. and E. A. Call: Esophageal Varices without Hepatic Cirrhosis. Arch. Path., 55:196, 1953. 8. Hollenbeck, C. A. and M. A. Adson: Eso phagogastric Varices without Hepatic Cir rhosis. Arch. Surg, 83:370, 1961. 9. Hsia, D. Yi-Y. and S. S. Cellis: Portal Hypertension in Infants and Children.' Amer. J. Dis. Children, 90:290, 1955. 10. Imanaga, H., S. Yamamoto and Y. Kuroyanagi: Surgical Treatment of Portal Hy pertension According to State of Intrahepatic Circulation. Ann. Surg., 155:42, 1962. 11. Kelsey, M. P, H. E. Robertson and H. Z. Ciffin: The Role of Chronic Thromboses of the Portal Vein and its Tributaries in the Syndrome of Splenic Anemia. Surg. Gynec. & Obstet, 83:289, 1947. 12. Klemperer, P.: Cavernomatous Transformation of the Porta] Vein: Its Relation to Banti's Disease. Arch. Path., 6:353, 1928. 13. McMichael, J.: The Pathology of Hepatolienal Fibrosis. I. Path. Bact, 39:481, 1934. 14. McXee, I. W.: Liver and Spleen: Their Clini cal and Pathological Associations. Brit. Med. J, 1:1111, 1932. 15. Mikkelsen, W. P.: Extrahepatic Portal Hyper tension in Children. Amer. T. Surg. In press. 16. Miller, M. C. and J. L. Brandt: Portal Hyper tension in the Absence of both Liver Dis ease and Vascular Obstruction. Amer. J. Dig. Dis., 7:442, 1962. 17. Murray, hi. J., A. P. Thai and R. Creenspan: Splenic Arteriovenous Fistulas as Cause of Portal Hypertension. Amer. J. Med., 29:849, 1960. 18. Pei-Lin Li:-Adaptation in Veins to Increased Intravenous Pressure, with Special Reference to the Porta] System and Inferior Vena Cava. J. Path. Bact, 50:121, 1940. 19. Pemberton, J. DeJ. and P. Kieman: Surgery of the Spleen. Surg. Clin. N. Amer., 25:880, 1945. 20. Polish, E., ). Christie, A. Cohen and B. Sul livan, Jr.: Idiopathic Prcsinusoidal Portal Hypertension. Ann. Intern. Med., 56:624, 21. Ratnoff, O. D, C. L. Conley and M. Bcrthrong: The Differentiation between Extrahepatic and Intrahepatic Obstruction of the Portal Circulation. Bull. Johns Hopkins Hosp, 87:305, 1950. 22. Ravenna, P.: Banti Syndrome (Fibrocongestive Splenomegaly). Arch. Intern. Med., 66: 879, 1940. 23. Reynolds, T. B. and A. C. Redcker: Hepatic Hemodynamics and Portal Hypertension in Popper, H. & F. Schaffner: Progress in Liver Disease. Vol. 2. New York, Grune & Strat ton. In press. 24. Reynolds, T. B,, A. C. Redeker and H. M. Celler: Technique for Verification of Wedg ing of Hepatic Venous Catheter. Gastro enterology, 38:799, 1960. 25. Reynolds, T. B,, A. G. Redeker and H. M. Celler: Wedged Hepatic Venous Pressure: A Clinical Evaluation. Amer. J. Med, 22: 341 1957. 26. Rousselot L. M.: The Late Phase of Conges tive Splenomegaly (Bands Syndrome) with Hematemesis out without Cirrhosis of the Liver. Surgery, 8:34, 1910. 27. Rousselot, L. M. and W. P. Thompson: Ex perimental Production of Congestive Spleno megaly. Proc. Soc. Exp. Biol. Med., 40:705, 1939. 28. Shaldon, S. and S. Sherlock: Obstruction to the Extrahepatic Portal System in Child hood. Lancet, 1:63, 1962. 29. Shillam, D. S.: Congestive Splenomegaly (Banti's Syndrome) Due to Portal Stenosis. Calif. Med, 67:379, 1947. 30. Siderys, H. and P. Veilios: Portal Hyperten sion without Cirrhosis or Extrahepatic Ob struction. Amer. J. Surg., 108:785, 1964. 31. Siroonds, J. P.: Chronic Occlusion of the Por tal Vein. Arch. Surg, 33:397, 1936. 32. Snavely, J. G. and E. S. Brcakell: Fatal Hemorrhage from Esophageal Varices. Amer. J. Med, 16:459, 1954. 33. Stone, H. H, IV. D. Jordan, J. A. Acker and J. D. Martin: Portal Arteriovenous Fistulas. Amer. J. Surg, 109:191, 1965. 34. Thompson, W. P.: The Pathogenesis of Banti's Disease. Ann. Intern. Med, 14:253, 1940. 35. Thompson, E. X, R. Williams and S. Sher lock: Liver Function in Extrahepatic Hartal Hypertension. Lancet, 2:1352, 1964. 36. Tisdak W. A, G. Klatskin and W. W. Glenn: Portal Hypertension and Bleeding Esopha geal Varices. Their Occurrence in the Ab sence of both Intrahepatic and Extrahepatic Obstruction of the Portal Vein. New Engl. J. Med, 261:209, 1959. 37. Wheeler, H. B. and R. Warren: Duodena] Varices due to Portal Hypertension from Arteriovenous Aneurysm. Ann. Surg, 146: 229, 1957. 38. Whipple, A. O.: The Problem of Portal Hy pertension In Relation to the Hepatosplenopathief. Ann. Surg, 122:449, 1945. 39. Wilson, J. B.: Changes in the Portal and Splenic Veins in Portal Hypertension and their Relation to Splenomegaly. Cut, 2r310, 1961. 24924017 Discvssiojr Dn. Charles Cartn-eh Child m (Ann Arbor, Mich.): I rise to make three points: one, an ex pression of appreciation to Dr. Mikkelsen for focus ing our attention on these patients who appear sporadically in almost all scries of patients with portal hypertension. We have all recognized them, usually by ones and by twos; I am amazed that Dr. Mikkelsen could find so many in his expert, ence. I can not help wondering what their basic problem really is. I think my second point is one of distress at having once again to consider Banti's disease. 1 would recall to you that in Dr. Banti's original description he pointed out that these were young people, originally with normal livers who went on Volume 162 Xember 4 HEPATOPORTAL SCLEROSIS 619 to develop big spleens, sometimes ascites and die the death of cirrhotic patients with portal hyper- tension. The third comment 1 would make is to tlocu* ment very briefly three patients in our experience with the picture Dr, Mikkelsen has outlined, in these we have done end-to-side portacaval shunts. If their livers were truly normal they should have gone on and died with the picture of the Eck Bstula dog. Dr. McDermott and I--and others-- have performed end-to-side portacaval shunts in patients with normal livers in association with re sections for pancreaticoduodenal cancer. They in variably presented the Eck-RstuIa-Pavlov-meat in toxication syndrome. The three patients with nor mal livers, portal hypertension and varices in whom we did end-to-side portacaval shunts have gone on and behaved just as individuals with cir rhosis in whom the conventional end-to-side porta caval shunt was performed. I am sure there is an additional dimension here that substantiates Dr. Mikkelsen's conception that these are not normal livers. On the other hand, it is v^iy hard for me to persuade my friends in pathology to give me much of a diagnosis other than a normal liver. I congratulate Dr. Mikkelsen on being able to identify these microscopic changes and calling them to our attention. I can assure you a good many of us are going to go hack ami review some of our previous liver biopsies. Dr. \V. Dean Warren (Miami): I would like to call your attention to one problem that exists in this very interesting group of patients. We have been interested in the syndrome of portal deprivation after portacaval shunts in ani mals with a normal liver and normal liver blood flow. As you know these animals do not tolerate portacaval shunt well and usually succumb within a few months. In the few humans who have been shunted with a normal liver and a normal, unoccluded portal vein, the postoperative course generally has been quite unsatisfactory. Now you will notice, from Dr. Mikkelsen's fig ures, that the group of patients having patent portacaval veins demonstrated a very high inci dence of portal encephalopathy, and a very high incidence of hepatic failure in the fairly early post operative course, despite preoperative normal or near-normal hepatic function tests. We believe that in most such instances the pa tient has a normal or near-normal liver blond flow. A portacaval shunt will immediately and dramati cally reduce the estimated hepatic blood flow to roughly 50 per cent of normal. If portacaval shunt ing is done in this type of patient 1 lx-licvc a high incidence of these very severe complications is inevitable. I would therefore like to make two pleas: first, that more hemodynamic data be obtained on the patients. We have had fust one such patient; she had a normal liver blood flow. Second, if opera tion is required, a nonshunting procedure is to be preferred in general. As you know, the bleeding can be controlled fairly well in this type of pa tient. I believe that this will lessen the chance of delayed motility or supply markedly. Dn. William W. L. Glenn (New Haven): The occurrence of porta] hypertension and bleed ing esophageal varices in the absence of both intrahepatic and extrahepatic obstruction has been recognized for some time. But we are indebted to Drs. Mikkelsen, Reynolds and Peters for their ex cellent report of their remarkably broad experi ence with this unusual condition. The cause of portal hypertension in patients without obvious venous obstruction remains ob scure. Undoubtedly, as the authors point out, there are pathologic changes in the livers, but they are by no means typical of cirrhosis. In some of these cases these changes might account for the in creased resistance to flow of blood in the hepatic venous radicles. In others, portal hypertension may be due, as the authors have demonstrated, to a partial occlusion of the portal vein caused by phlebosclerosis. There remain, however, a few pa tients with no demonstrable lesion of the liver or the vein to account for the increase in vascular resistance. Since the blood pressure within the portal sys tem depends on the volume of, as well as on the resistance to, blood flow, it is reasonable to sup pose that certain cases of otherwise unexplained portal hypertension may result from abnonnalitics of fate through an otherwise normal splenoportal axis. Such was the situation, we believed, in four cases of portal hypertension without portal ob struction that we reported in collaboration with Drs. Tisdale and Klatskin. After failure to demonstrate the factors respon sible for portal hypertension in our four patients, we were led to conjecture that either an increase in blood Bow in the portal system or functional changes, such as an increase in venous tone, was the cause of the hypertension. The liver biopsies in these patients were normal --or nearly normal--at the time of operation and before, and in two of the patients 2 and 4 years postoperathefy. Theoretically, an increase in the volume of blood entering the portal vein--or en tering the portal system--may lead to sustained portal hypertension. Practically, this concept is proved Ivy the dem onstration of portal hypertension ami its conse quences in some patients with arteriovenous fistulas involving the splenoportal axis. I would like to ask the authors if they have made any direct observations on blood flow in the portal vein in their cases, and also, do they have any opinion as to the role of venous tone as the cause of increased resistance to flow through the portal system. Dr. Richard M. Peters (Chapel Hill): I merely want to ask a question very similar to Dr. Glenn's. Were any cardiac outputs measured in SXOfZGXZ ^pG364i$ 620 M1KKELSEN AND OTHERS Aaaals of Sargety October 1965 these patients? It may well be that the reason they will not tolerate a shunt procedure is that the blood flow through the liver is low. If one found that they did not have the elevation in cardiac output which most cirrhotics do, one woukl ex pect that their liver would not tolerate a shunting procedure. Dr. Lovis M. Rocsselot (New York): 1 reiter ate Gardner Childs belief--not belief but state ment--as to the paucity of these eases, and we would also like to add that same note. This group of cases is extremely rare. I suspect there is some geographic variation on this. The Italians see a considerable number of these cases. \Ye hare not seen nearly as many in the East I would also like to add an historic note in sup port of the New Haven group's contention that this may be primarily a functional derangement with these anatomic changes developing later in many of these cases. Essex, over 30 years ago at the Mayo Clinic, postulated a state of chronic vasospasm in the-- either in the sinusoidal or presinusnidal area, and he was able to produce experimentally a state of temporary portal hypertension, using some ascaris extract This is an extremely interesting group of cases and I agree with the author that the surgical man agement should be one of very selective distinc tion and not necessarily total portal bed decom pression. Dr. William P. Mikkelsen (Closing): Unfor tunately, we have been repeatedly thwarted in our etforts to obtain good hemodynamic data on this group of patients. In the 12 patients so studied, hepatic blood flow has been reduced consistently and wedged hepatic vein pressure has been nor mal. This has been tme for those with an open as well as those with an occluded portal vein. Un fortunately, cardiac output has not been measured. In a few patients fnnn each of the three groups, plasma volume, red cell mass and whole blood volume recently have been measured. In all pa tients studied these values have been elevated alxne normal, just as they are in cirrhosis. The implication of this fact is thus far occult. Dr. Rousselot must be correct when he suggests that there may be geographic differences in the incidence of this disease. For example, nearly half of the patients with portal hypertension seen by the Nagoya group in Japan are representatives of this or a similar category. It would be wrong to leave the impression that all of these patients do poorly. Actually, most do well. 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