Friedrich Längle

Current value of intraoperative sonography during surgery for hepatic neoplasms

Noninvasive liver imaging has developed rapidly resulting in increased accuracy for detecting primary and secondary hepatic tumors. Intraoperative ultrasonography (IOUS) was commonly considered to be the gold standard for liver staging, but the current value of IOUS is unknown in view of more sophisticated radiologic tools. The purpose of this prospective study was to evaluate the impact of IOUS on the treatment of 149 patients undergoing liver surgery for malignant disease (colorectal metastasis, 61 patients; hepatoma, 52 patients; other hepatic malignant tumors, 36 patients). The sensitivities of computed tomography (CT), helical CT, magnetic resonance imaging, and IOUS in patients with colorectal metastases were 69.2%, 82.5%, 84.9%, and 95.2% in a segment-by-segment analysis; in patients with hepatoma their sensitivities were 76.9%, 90.9%, 93.0%, and 99.3%; and in patients with other hepatic malignancies they were 66.7%, 89.6%, 93.3%, and 98.9%, respectively. Additional malignant lesions (AMLs) were first detected by inspection and palpation in 20 patients (13.4%). In another 18 patients (12.1%) IOUS revealed at least one AML. Overall, the findings obtained only by IOUS changed the surgical strategy in 34 cases (22.8%). It was concluded that IOUS, having undergone some refinement as well, still has immense diagnostic value in hepatectomy candidates. Frequently avoiding palliative liver resection and occasionally disproving unresectability as assessed by preoperative imaging, IOUS still has a significant impact on surgical decision making and should still be considered the gold standard.RésuméOn a récemment assisté à une amélioration importante dans la précision de la détection des tumeurs primitives et secondaires du foie par l’imagerie non-invasive. L’échographie peropératoire (EPO) a été considérée comme l’examen de référence («gold standard») dans le Staging du foie, mais la valeur de l’EPO est discutée à présent en raison de l’apparition d’investigations radiologiques plus sophistiquées. Le but de cette étude prospective a été d’évaluer l’impacte de l’EPO au cours d’une résection hépatique pour maladie maligne chez 149 patients (métastases d’origine colorectale: 61 patients; carcinome hépatocellulaire: 52 patients; autres tumeurs hépatiques malignes: 36 patients). Chez les patients ayant des métastases d’origine colorectale, la sensibilité de la tomodensitométrie simple (TDM), de la tomodensitométrie hélicoïdale (TDMh), de la résonance magnétique (RM) et l’EPO a été de 69.2%, 82.5%, 84.9% et 95.2% dans une analyse du foie segment par segment. Chez les patients porteurs de carcinome hépatocellulaire, la sensibilité de ces différentes méthodes était, respectivement, de 76.9%, 90.9%, 93% et 99.3%; chez les patients ayant d’autres tumeurs malignes du foie, la sensibilité était, respectivement, de 66.7%, 89.6%, 93.3% et 98.9%. D’autres lésions malignes ont été détectées à l’inspection et à la palpation chez 20 patients (13.4%). De plus, chez 18 autres patients (12.1%), l’EPO a décelé au moins une lésion maligne supplémentaire. Globalement, les données obtenues par l’EPO ont changé la stratégie chirurgicale dans 34 cas (22.8%). On conclue que l’EPO, grâce à quelques raffinements, a toujours une immense valeur diagnostique pour les candidats à l’hépatectomie. En évitant à certains patients une résection palliative, et en permettant, de temps à autre, une résection jugée impossible par les investigations préopératoires, l’EPO garde un impacte significatif sur la décision chirurgicale et devrait continuer à être le «gold standard».ResumenEl rápido desarrollo de los métodos no invasivos ha conferido una mayor precisión diagnóstica de los tumores hepáticos tanto primarios como secundarios. La ecografÍa intraoperatoria (IOUS) se consideró como el mejor método diagnóstico para la estadificación hepática, pero en la actualidad, su valor está en entredicho ante los nuevos y sofisticados estudios radiológicos. El objetivo de este estudio prospectivo fue evaluar el valor de la IOUS en el tratamiento quirúrgico de 149 pacientes con neoplasias malignas de hÍgado (metástasis colorrectales n=61; hepatomas n=52; otros tumores hepáticos malignos n=36). El análisis secuencial segmentario demostró en pacientes con metástasis colorrectales una sensibilidad para la tomografÍa axial o helicoidal computarizada (CT y hCT) del 69.2% y 82.5%, para la resonancia magnética nuclear (MR) del 84.9% y para la IOUS del 95.2%. En pacientes con hepatomas la sensibilidad de estos métodos fue del 76.9%, 90.9%, 93% y 98.9%. En 20 pacientes (13.4%) lesiones malignas adicionales (AML) se diagnosticaron por inspección y palpación. En otros 18 pacientes (12.1%) la IOUS fue capaz de detectar al menos una AML. En 34 casos (22.8%) el conjunto de hallazgos obtenidos exclusivamente con la IOUS propició un cambio de estrategia quirúrgica. En conclusión, la IOUS, con sus recientes mejoras, sigue teniendo un inmenso valor diagnóstico para aquellos que son candidatos a una hepatectomÍa. Previene, con frecuencia, las resecciones hepáticas paliativas y, ocasionalmente, contradice el diagnóstico de irresecabilidad obtenido con otros medios diagnósticos. La IOUS sigue teniendo un importante valor a la hora de establecer una decisión quirúrgica y continúa siendo el mejor método diagnóstico.

Is inadequate thrombopoietin production a major cause of thrombocytopenia in cirrhosis of the liver

BACKGROUND/AIMS Thrombocytopenia secondary to cirrhosis of the liver and portal hypertension is a well-known complication of advanced stage liver disease, but theories about the underlying pathogenetic mechanisms, mostly centering on splenic sequestration and destruction of platelets, have failed to solve the problem so far. METHODS Peripheral platelet count and thrombopoietin levels in human plasma were measured in 28 patients with cirrhosis of the liver. Seven of those patients underwent orthotopic liver transplantation and five patients portal decompression by transjugular intrahepatic portosystemic shunt. Thrombopoietin plasma levels were followed for 14 days after the interventions. RESULTS No measurable thrombopoietin was detectable in the plasma of 28 thrombocytopenic patients with cirrhosis of the liver, in contrast to thrombocytopenic patients without liver disease. Seven of these patients with cirrhosis underwent orthotopic liver transplantation, resulting in a rise of thrombopoietin levels within 2 days after transplantation. The rise in platelet number followed with a mean lag of 6 days, and shortly thereafter, thrombopoietin levels returned to levels below the limit of detection. Five patients with thrombocytopenia, who underwent only decompression of portal hypertension, showed no rise in either thrombopoietin levels or platelet count. CONCLUSIONS Thrombocytopenia associated with liver disease may at least in part be attributable to inadequate thrombopoietin production in the failing liver.

Arginase release following liver reperfusion : evidence of hemodynamic action of arginase infusions

Immediately after hepatic reperfusion in human or-thotopic liver transplantation, high amounts of arginase are released from the graft, thereby influencing nitric oxide metabolism. This metabolic alteration may be one component of the ischemia-reperfusion syndrome in OLT with its hemodynamic disturbances (e.g., systemic hypotension, pulmonary hypertension). The aim of this study was to compare hemodynamic and metabolic changes following OLT in the pigs with those obtained under arginase infusions in catheterized, anesthetized pigs. Following liver revascularization in the pigs, plasma arginase concentrations increased from 48±19 IU/L to 2613 ±944 IU/L, resulting in a drop in plasma levels of L-arginine (-87%) and in a drop in nitrite (-82%) and nitrate (-53%) concentrations. Of the measured organspecific hemodynamic alterations, the mean pulmonary arterial pressure increased from 17±2 mmHg to 30±5 mmHg, whereas the flow/pressure index of the portal vein decreased about 60%. A primed continuous infusion of arginase (25,000 IU) increased plasma arginase levels to a maximum of 3,690±962 IU and evoked a decrease of L-arginine, but did not alter plasma nitrite or nitrate levels. The administration of arginase in healthy pigs did not influence cardiac output, mean arterial pressure, heart rate, or total peripheral resistance, but led to an increase of mean pulmonary arterial pressure from 19±3 to 48±5 mmHg and to a reduction of arterial hepatic blood flow from 229±65 ml/min to 154±41 ml/min. From this we conclude that high levels of liver arginase cause hemodynamic alterations in the lung and the liver. We hypothesize that the pulmonary hypertension and the reduced hepatic blood flow found during the immediate reperfusion period after OLT are possibly related to the increased arginase release due to the hepatic damage of the graft.

The role of intra-abdominal pressure on splanchnic and pulmonary hemodynamic and metabolic changes during carbon dioxide pneumoperitoneum

BACKGROUND AND METHODS To find an intra-abdominal pressure (IAP) range for laparoscopic procedures that elicits only moderate splanchnic and pulmonary hemodynamic and metabolic changes, including hepatic and intestinal tissue pH and superficial hepatic blood flow, we installed an IAP of 7 and 14 mm Hg each for 30 minutes in 10 healthy pigs (30 +/- 4 kg). RESULTS In parallel with the increase of IAP, the mean transmural pulmonary artery pressure increased (from 25 +/- 3 to 27 +/- 4 at 7 mm Hg IAP and 30 +/- 6 mm Hg at 14 mm Hg IAP, p < 0.05); the pulmonary artery-to-pulmonary capillary wedge pressure gradient also increased (from 17 +/- 2.7 to 21 +/- 3 mm Hg at 7 mm Hg IAP and 24 +/- 4.2 mm Hg at 14 mm Hg IAP, p < 0.01), and the arterial oxygenation decreased (p < 0.005). Relevant changes at an IAP of 14 mm Hg were observed in right atrial pressure during inspiration (from 7 +/- 2 to 12 +/- 3 mm Hg, p < 0. 0001) and in abdominal aortic flow (from 1.43 +/- 0.4 to 1.19 +/- 0. 3 L/min, p < 0.01). However, transmural right atrial pressure and cardiac output remained essentially unchanged. Portal and hepatic venous pressure increased in parallel with the IAP (portal: from 12 +/- 3 to 17 +/- 3 at 7 mm Hg IAP and 22 +/- 3 mm Hg at 14 mm Hg IAP, p < 0.01; hepatic venous: from 8 +/- 3 to 14 +/- 6 at 7 mm Hg IAP and 19 +/- 6 mm Hg at 14 mm Hg IAP, p < 0.005), but the transmural portal and hepatic venous pressures decreased (p < 0.01), indicating decreased venous filling. Portal flow was maintained at 7 mm Hg but decreased at 14 mm Hg from 474 +/- 199 to 395 +/- 175 mL/min (p < 0. 01), whereas hepatic arterial flow remained stable. Hepatic superficial blood flow decreased during insufflation and increased after desufflation. Tissue pH fell together with portal and hepatic venous pH (intestinal: from 7.323 +/- 0.05 to 7.217 +/- 0.04; hepatic: from 7.259 +/- 0.04 to 7.125 +/- 0.06, both p < 0.01) at 14 mm Hg. CONCLUSION The hemodynamic and metabolic derangement in the pulmonary and splanchnic compartments are dependent on the extent of carbon dioxide pneumoperitoneum. The effect of low IAP (7 mm Hg) on splanchnic perfusion is minimal. However, higher IAPs (14 mm Hg) decrease portal and superficial hepatic blood flow and hepatic and intestinal tissue pH.

Radical Surgical Therapy of Abdominal Cystic Hydatid Disease: Factors of Recurrence

Abstract. A series of 74 consecutive patients (48 women, 26 men) were operated for abdominal hydatid disease between June 1949 and December 1995. The patients ranged in age from 15 to 81 years (median 49 years). In 69 cases only the liver was affected; two patients had concomitant extrahepatic disease (one spleen, one spleen and lung), and 3 had cysts in the spleen only. Cysts were multiple in 11 patients and calcified in 24. Conservative surgical procedures were used for 22 cysts in 20 patients [open partial (n= 3), open total (n= 6), closed total cystectomy (n= 9), marsupialization (n= 2), drainage (n= 2)] and radical surgical procedures for 72 cysts in 54 patients [pericystectomy (n= 41), wedge liver resection or hemihepatectomy (n= 25), splenectomy (n= 5), radical resection of a lung cyst (n= 1)]. Altogether 37 patients (50%) were given perioperative antihelmintic chemotherapy with mebendazole (18 patients) or albendazole (19 patients). Operative mortality rates were 5.0% after conservative surgery and 1.8% after radical surgery. Morbidity rates were 25.0% following conservative surgery and 24.1% following radical surgery. Antihelmintic therapy was well tolerated by all but five patients. All side effects were entirely reversible. Among the 74 patients, 60 (81.0%) were available for long-term follow-up (median 7.2 years; range 2.0–47.0 years). Recurrence of disease was seen in 9 of 60 patients at an interval of 3 months to 20 years from the first operation. The rate of recurrence was significantly lower after radical surgical procedures (p= 0.03) and after closed removal of the cyst (p= 0.04).

Analysis of hepatic resection of metastasis originating from gastric adenocarcinoma

Few patients with metastatic gastric cancer have disease that is amenable to curative surgery. Thus far, little is known about liver surgery for metastases arising from gastric adenocarcinoma and prognostic factors. Of 73 patients operated on between 1980 and 1999 for noncolorectal, non-neuroendocrine hepatic metastases, 15 underwent liver resection for gastric adenocarcinoma metastasis. Ten patients underwent synchronous hepatic resection and five underwent metachronous hepatic surgery after a median diseasefree interval of 10 months (range 6.1 to 47.3 months). None of the patients died within the first 30 days after surgery, and the in-hospital mortality rate was 6.7%. Among patients in the synchronous group, 26.7% experienced major complications mainly associated with gastric surgery. Overall median survival was 8.8 months (range 4 to 51 months); two patients survived more than 3 years. Univariate analysis reealed that the appearance of liver metastasis synchronous vs. metachronous), the distribution of liver metastases (unilobar vs. bilobar), and the primary tumor site (proximal vs. distal) were marginally signifiant predictive factors regarding overall survival. Because of its high morbidity, synchronous liver resecion for metastases originating from gastric adenocarcinoma is rarely followed by survival longer than 2 years. Primary tumor localization within the proximal third of the stomach and bilobar liver involvement appear to be predictive of poor outcome. On the other hand, curative resection of metachronous liver metastases may allow long-term survival in selected patients.

L-arginine deficiency after liver transplantation as an effect of arginase efflux from the graft : influence on nitric oxide metabolism

L-Arginine plays an important role in protecting animals against ammonia intoxication, enhances immune function, stimulates wound healing, and is the precursor for the endothelium-derived relaxing factor, recently recognized as nitric oxide (NO). In this study, we investigated the influence of hepatic reperfusion on amino acid metabolism after human OLT. After 10 sec of reperfusion, the arterial plasma levels of L-arginine dropped from 105 +/- 12 mumol/L to 3.8 +/- 0.6 mumol/L (P < 0.001), whereas plasma ornithine increased from 40 +/- 5.5 mumol/L to 129 +/- 15 mumol/L (P < 0.001). The reduced L-arginine levels remained subnormal for several hours after OLT. This drop in plasma L-arginine was due to an arginase release from the implanted graft. Immediately after reperfusion, the plasma concentrations of arginase increased from pretransplantation values of 18 +/- 13 IU/L to 2384 +/- 1456 IU/L (P < 0.01). Measurement of plasma nitrite (NO2-) and nitrate (NO3-), which are the stable end products of NO, revealed that NO2- decreased about 50% after reperfusion (from 1.64 +/- 0.32 mumol/L to 0.80 +/- 0.17 mumol/L; P < 0.001), whereas NO3- levels remained unchanged (76 +/- 23 mumol/L vs. 63 +/- 8 mumol/L). We conclude that hepatic reperfusion causes L-arginine deficiency by liberating high amounts of arginase from the implanted graft. This L-arginine depletion may influence the NO synthesis in patients after OLT.

Organ survival after primary dysfunction of liver grafts in clinical orthotopic liver transplantation

Abstract In a retrospective analysis of 632 orthototopic liver transplant procedures performed between 1982 and 1997, the incidence of primary dysfunction (PDF) of the liver and its influence on organ survival were studied. Graft function during the first 3 postoperative days was categorized into four groups: (1) good (GOT max < 1000 U/l, spontaneous PT > 50 %, bile production > 100 ml/day); (2) fair (GOT 1000‐2500 U/l, clotting factor support < 2 days, bile < 100 ml/day); (3) poor (GOT > 2500 U/l, clotting factor support > 2 days, bile < 20 ml/day); (4) primary non‐function (PNF; retransplantation required within 7 days). The aim of this study was to evaluate graft survival comparing organs with PDF (poor function) and PNF vs organs with initial good or fair function. After a median follow‐ up of 45 months, initially good and fair function of liver grafts resulted in a significantly better long‐term graft survival compared with grafts with initially poor function or primary non‐function (if re‐transplanted) (P < 0.01). The Cox model revealed primary function as a highly significant factor in the prediction of long‐term graft survival (P < 0.0001). We conclude that these results confirm the hypothesis that primary graft function is of major importance for the long‐term survival of liver transplants. Patients with a poor primary function have the worst survival prognosis, which leads to the interpretation that these patients may be candidates for early retransplantation.

Stage-dependent Therapy of Rectal Carcinoid Tumors

Abstract. Although malignant behavior of rectal carcinoid tumors is rare, the risk of metastases and death does exist. Adaptation of therapy according to the estimated malignancy seems necessary. To develop a stage-dependent therapy, 31 patients with rectal carcinoid tumors measuring 5 to 50 mm in diameter were analyzed retrospectively. Malignancy was estimated according to tumor size, infiltration depth, and histopathology. There were 18 tumors within the mucosa and submucosa (T1), 7 tumors with muscularis propria invasion (T2), and carcinoid tumor penetrating the full rectal wall (T3) or spreading to surrounding tissue (T4) in 6 patients. Altogether 20 patients (65%) were treated with a minimally invasive intervention: endoscopic polypectomy (EP) in 12 and transanal excision (TE) in 8 patients. In 11 patients (35%) aggressive surgical procedures—anterior resection (AR) in 4 and abdominoperineal resection (APR) in 7—were performed. After a mean ± SD follow-up of 86.0 ± 61.3 months, tumor recurrence was not seen in any of the 20 patients with minimally invasive treatment, and all were still alive. No severe complications associated with surgical procedures were detected. In contrast, 5 of the 10 patients with advanced tumor stage died from their disease despite aggressive surgery (AR, APR). In conclusion, depending on tumor stage, treatment of rectal carcinoids includes EP, TE, or extended resection. Minimally invasive techniques are safe treatments for small to medium-size T1/T2 rectal carcinoids. Extended surgery cannot improve the overall survival of those with advanced tumors (T3/T4, N1, M1) but can be beneficial for preventing local complications.

Accuracy of Multiphasic Helical Computed Tomography and Intraoperative Sonography in Patients Undergoing Orthotopic Liver Transplantation for Hepatoma: What is the Truth?

ObjectiveTo determine the real value of liver imaging in cirrhosis by macro- and histomorphologic examination of the entire organ after orthotopic liver transplantation for hepatocellular carcinoma (HCC). Summary Background DataIn comparative studies, a virtual sensitivity of up to 94% is described for helical computed tomography in HCC staging. The tumor detection rate of intraoperative ultrasonography (IOUS) is reported to be almost 100%. MethodsThis prospective observational study comprised 23 patients with HCC in cirrhosis admitted for orthotopic liver transplantation. Results of preoperative triphasic helical computed tomography (HCT) and IOUS were correlated with histopathologic results after 3-mm-slicing of the explanted liver. ResultsOverall, 179 liver segments were examined by HCT, IOUS, and MHM. Fifty-two malignant lesions and 10 dysplastic nodules were revealed by MHM. Using HCT, 13 HCCs could not be identified in 8 patients and 15 results were falsely positive in 10 patients. The detection rate of dysplastic nodes was 40% for HCT and 60% for IOUS. IOUS missed four HCCs in four patients and had six false-positive results in six patients. In a segment-based analysis, the overall accuracy of IOUS was significantly higher for IOUS (95.5%) versus HCT (89.9%). In the lesion-by-lesion analysis, the sensitivity was 92.3% for IOUS and 75.0% for HCT, with a significant difference. ConclusionsCorrelation of explanted liver pathologic results offers precise evaluation of imaging modalities. The data of this histopathologically based study confirm that IOUS is significantly superior in staging HCC in cirrhosis versus CT, even after technical refinements through enhanced multiphasic high-velocity helical scanning.