Arved Weimann

Surgical treatment in proximal bile duct cancer. A single-center experience.

OBJECTIVES The authors evaluated the experience and results of a single center in surgical treatment of proximal bile duct carcinoma. SUMMARY BACKGROUND DATA Whenever feasible, surgery is the appropriate treatment in proximal bile duct carcinoma. To improve survival rates and with special regard to liver transplantation, the extent of surgical radicalness remains an open issue. PATIENTS AND METHODS Retrospective analysis of 249 patients who underwent surgery for proximal bile duct carcinoma via the following procedures: resection (n = 125), liver transplantation (n = 25), and exploratory laparotomy (n = 99). Survival rates were calculated according to the Kaplan-Meier method, uni- and multivariate analysis of prognostic factors, and log rank test (p < 0.05). RESULTS Survival rates after resection and liver transplantation are correlated with international Union Against Cancer (UICC) tumor stage (resection: overall 5-year, 27.1%; stage I and II, 41.9%; stage IV, 20.7%; liver transplantation: overall 5-year, 17.1%; stage I and II, 37.8%; stage IV, 5.8%). Significant univariate prognostic factors for survival after liver resection were lymph node involvement (N category), tumor stage, tumor-free margins, and vascular invasion; for transplantation, they were local tumor extent, N category, tumor stage, and infiltration of liver parenchyma. For resection and transplantation, a multivariate analysis showed prognostic significance of tumor stage and tumor-free margins. CONCLUSION Resection remains the treatment of choice in proximal bile duct carcinoma. Whenever possible, decisions about resectability should be made during laparotomy. With regard to the observation of long-term survivors, liver transplantation still can be justified in selected patients with stage II carcinoma. It is unknown whether more radical procedures, such as liver transplantation combined with multivisceral resections, will lead to better outcome in advanced stages. With regard to palliation, surgical drainage of the biliary system performed as hepatojejunostomy can be recommended.

Resectional surgery of hilar cholangiocarcinoma: a multivariate analysis of prognostic factors.

PURPOSE To define the prognostic factors after surgical resection of bile duct carcinomas at the hepatic bifurcation. PATIENTS AND METHODS The retrospective single-center experience details 151 patients after surgical resection of central bile duct carcinoma performed between 1971 and 1995. Tumor removal was accomplished by resection of the bile duct bifurcation either alone (group I, n = 33), in combination with hepatic resection (group II, n = 77), or combined with hepatic and vascular resection (group III, n = 41). Survival analysis was performed by the Kaplan-Meier method and the relationship between each of the clinicopathologic variables and survival was assessed by the log-rank test. Multivariate results were confirmed using Cox regression. RESULTS The overall hospital mortality rate was 9.9% and depended on the extent of resection (group 1, 6.1%; group II, 7.8%; group III, 17.1%). After exclusion of hospital deaths, the overall patient survival rate was 28.4% at 5 and 15.5% at 10 years, with a median survival duration of 2.05 +/- 0.23 years. Univariate survival analysis identified tumor size, lymph node metastases, residual tumor stage, and tumor grading as factors with a statistically significant prognostic impact. Survival prognosis was not influenced by the site of the tumor according to the classification of Bismuth and Corlette, extent of resection, International Union Against Cancer (UICC) stage, perineural and vascular invasion, age, or sex. In a multivariate Cox analysis, only lymph node metastases and residual tumor stage proved to be of independent prognostic significance. CONCLUSION Resection of central bile duct carcinoma is feasible in many patients and a favorable outcome after resection is mainly determined by curative resection and the absence of lymph node metastases.

Benign Liver Tumors: Differential Diagnosis and Indications for Surgery

Abstract. The differential diagnosis for hemangioma, focal nodular hyperplasia (FNH), and hepatocellular adenoma may be difficult. Reliable diagnosis is mandatory for the decision of whether to apply surgery or observation. Experience with long-term observation in nonoperated patients with hemangioma and FNH is limited. A group of 437 patients from a single institution were analyzed with regard to a diagnostic algorithm, the indications for surgery, and observation. There were 238 hemangiomas, 150 cases of FNH, 44 adenomas, and 5 mixed tumors. Of the 437 patients, 173 underwent surgery; 103 with hemangioma and 54 with FNH were observed at our own institution, whereas 117 patients underwent follow-up elsewhere or were lost. Among the operated patients with confirmed histology, a good diagnostic yield was found for a combination of ultrasonography (US), contrast (bolus)-enhanced computed tomography (CT), and labeled red blood cell (RBC) scanning: sensitivity 85.7%, specificity 100%, positive predictive value (PPV) 100%, negative predictive value (NPV) 81.8%, and accuracy 91.3%. For FNH the combination of US and CT plus cholescintigraphy showed a sensitivity 82.1%, specificity 97.1%, PPV 95.8%, NPV 84.6%, and accuracy 90.3%. Surgical mortality was 0.6%. Observation of patients with hemangioma and FNH for a median of 32 months revealed no increase in tumor size in 80% and a decrease in fewer than 7%. There was no tumor rupture and no evidence of malignant transformation. We concluded that liver hemangioma and FNH can be differentiated from adenoma with high sensitivity, specificity, and accuracy by labeled RBC scanning and cholescintigraphy in combination with US and contrast-enhanced CT. In the case of symptoms or an equivocal diagnosis with respect to adenoma or hepatocellular carcinoma, surgery can be performed with very low risk. Because in asymptomatic patients with observed hemangioma or FNH no increase of tumor size can be expected for many years, the indications for surgery must be carefully evaluated.

Recurrence Patterns of Hepatocellular and Fibrolamellar Carcinoma After Liver Transplantation

PURPOSE Tumor recurrence is the major limitation of long-term survival after liver transplantation for hepatocellular carcinoma (HCC) or fibrolamellar carcinoma (FLC). Understanding tumor-biologic characteristics is important for selection of patients and for development of adjuvant therapeutic strategies. PATIENTS AND METHODS The study included 69 patients who underwent potentially curative liver transplantation for HCC/FLC and survived for more than 150 days; minimum follow-up was 33 months. Frequency, localization, and timing of recurrence were analyzed and compared with primary tumor and patient characteristics. RESULTS Tumor recurrence was observed in 39 patients at 67 locations. Hematogenous spread was the major route of tumor recurrence (87%), and the most frequent sites were the liver (62%), lung (56%), and bone (18%). Parameters associated with recurrence were absence of cirrhosis, tumor size greater than 5 cm, more than five nodules, vascular infiltration, and International Union Against Cancer (UICC) stage IVA. Selective intrahepatic recurrence was found in nine patients (23%); it was associated with highly differentiated tumors, lack of vascular infiltration, and male sex. Recurrence at multiple sites was found predominantly in young patients (< or = 40 years) and for multicentric (> 5) primary tumors. Recurrences were observed within a wide time range after transplantation (43 to 3,204 days; median, 441 days); late recurrences (> 1,000 days, n = 8) were associated with highly differentiated or fibrolamellar tumors and low UICC stages. Surgical treatment was the only therapeutic option associated with prolonged survival after recurrence. CONCLUSION In transplant recipients, hepatocellular carcinomas vary considerably in their pattern and kinetics of metastases. Tumor cells may persist in a dormant state for long time periods before giving rise to clinical metastases. Surgical treatment of recurrence should be considered whenever possible.

Influence of arginine, omega-3 fatty acids and nucleotide-supplemented enteral support on systemic inflammatory response syndrome and multiple organ failure in patients after severe trauma

This study investigated the influence of an enteral diet supplemented with arginine, omega-3 fatty acids, and nucleotides (Impact, Sandoz Nutrition, Berne, Switzerland) on the incidence of systemic inflammatory response syndrome (SIRS) and multiple organ failure (MOF) in patients after severe trauma. Thirty-two patients with an injury-severity score > 20 were included in this prospective, randomized, double-blind, controlled study. Primary endpoints were the incidence of SIRS and MOF. Secondary endpoints were parameters of acute phase and immune response as well as infection rate, mortality, and hospital stay. For statistical analysis 29 patients (test group n = 16, control n = 13) were eligible. In the test group, significantly fewer SIRS days per patient were found during 28 d. The difference was highly significant between d 8-14 (P < 0.001). MOF score was significantly lower in the test group on d 3 and d 8-11 (P < 0.05). Acute phase parameters showed lower C-reactive protein serum levels (significant on D day 4) and fibrinogen plasma levels (significant on d 12 and 14; P < 0.05). HLA-DR expression on monocytes showed significantly higher fluorescence activity on d 7. No significant difference was found for T-lymphocyte CD4/CD8 ratio, interleukin-2 receptor expression, infection rate, mortality (2/16 vs. 4/13), and hospital stay. The results of the study provide further support for beneficial effects of arginine, omega-3-fatty acids and nucleotide-supplemented enteral diet in critically ill patients.

Liver transplantation for metastatic neuroendocrine tumors

OBJECTIVE This article describes the experience with liver transplantation in patients with irresectable neuroendocrine hepatic metastases. SUMMARY BACKGROUND DATA Liver transplantation has become an established therapy in primary liver cancer. On contrast, there is little experience with liver transplantation in secondary hepatic tumors. So far, in the majority of patients being transplanted for irresectable liver metastases, long-term results have been disappointing because of early tumor recurrence. Because of their biologically less aggressive nature, the metastases of neuroendocrine tumors could represent a justified indication for liver grafting. METHODS In a retrospective study, the data of 12 patients who underwent liver transplantation for irresectable neuroendocrine hepatic metastases were analyzed regarding survival, tumor recurrence, and symptomatic relief. RESULTS Nine of 12 patients currently are alive with a median survival of 55 months (range, 11.0 days to 103.5 months). The operative mortality was 1 of 12, 2 patients died because of septic complications or tumor recurrences or both 6.5 months and 68.0 months after transplantation. all patients had good symptomatic relief after hepatectomy and transplantation. Four of the nine patients who are alive have no evidence of tumor with a follow-up of 2.0, 57.0, 58.0, and 103.5 months after transplantation. CONCLUSIONS In selected patients, liver transplantation for irresectable neuroendocrine hepatic metastases may provide not only long-term palliation but even cure. Regarding the shortage of donor organs, liver grafting for neuroendocrine metastases should be considered solely in patients without evidence of extrahepatic tumor manifestation and in whom all other treatment methods are no longer effective.

Arterial chemoembolization before liver transplantation in patients with hepatocellular carcinoma: marked tumor necrosis, but no survival benefit?

BACKGROUND/AIMS Hepatic artery chemoembolization was introduced in the treatment of patients with unresectable hepatocellular carcinoma waiting for liver transplantation. The rationale for this preoperative treatment was to control tumor growth during the waiting period and to improve long-term survival. This study aimed to investigate whether preoperative chemoembolization not only induces marked tumor necrosis but also has a survival benefit. METHODS In this study 21 patients with hepatocellular carcinoma who underwent pretransplant chemoembolization (group I) were compared with 21 historical control patients (group II) without preoperative chemoembolization in a case-control study. The number of pretransplant chemoembolizations in each patient in group I varied between 1 and 5 with a mean of 2.44+/-1.15. In addition, six patients of this group received preoperative systemic chemotherapy. RESULTS Overall, there were no differences in survival between the groups with and without pretransplant chemoembolization at 1 year (60.8% vs 61.5%) and at 3 years (48.4% vs 53.9%). In group I, three patients developed unexplained severe pneumonia, leading to death very early after liver transplantation. Marked tumor necrosis (>50%) was found in 14 cases in group I. In 6 out of these 14 patients, total tumor necrosis was observed. CONCLUSION Although preoperative chemoembolization or chemotherapy induced marked tumor necrosis, these patients showed no benefit in survival compared to historical controls, and appeared to be at higher risk of developing immediate postoperative infective complications.

Appraisal of transplantation for malignant tumours of the liver with special reference to early stage hepatocellular carcinoma

The enthusiasm to treat or even cure patients with unresectable hepatobiliary malignancy by total hepatectomy and liver transplantation has considerably diminished. Nowadays, due to organ-donor shortage, patients have to be selected with predictable likelihood for long-term survival. According to own experience and a review of the literature, liver transplantation may be considered in unresectable early stage hepatocellular and proximal bile duct carcinoma, the uncommon entities fibrolamellar carcinoma, epithelioid haemangioendothelioma and hepatoblastoma as well as in liver metastases from neuroendocrine tumours. At present, advanced stages of hepatocellular and proximal bile duct carcinoma, as well as intrahepatic bile duct carcinoma, haemangiosarcoma and metastases from nonendocrine tumours, should be excluded from transplantation. In order to cure the cancer-bearing disease, liver transplantation might be the ideal treatment for small but still resectable hepatocellular carcinoma with underlying cirrhosis. Our retrospective comparison of survival after resection and transplantation for early stage hepatocellular carcinoma does not reveal a significant difference. Although a tendency has been observed in favour of transplantation, resection of these tumours is still justifiable, not least because of donor organ shortage.

Ergebnisse der Resektion nichtcolorectaler nichtneuroendokriner Lebermetastasen

Summary. Over a period of 11 years a total of 140 liver resections for non-colorectal, non-neuroendocrine hepatic metastases were performed in 127 patients (73 women, 54 men; median age 53 years). There were 120 first, 14 second and 6 third liver resections. Primary tumors were: breast cancer (n = 34), leiomyosarcoma (n = 20), pancreatic cancer (n = 16), renal cell carcinoma (n = 13), melanoma (n = 9), gastric cancer (n = 9), lung cancer (n = 6) and adrenal cancer (n = 6) and miscellaneous tumors (n = 14). Extrahepatic tumor manifestation (including synchronous primary tumors) was found in 69/140 cases (49 %); 61 of 120 patients with a first liver resection had extrahepatic tumor (51 %). In the 120 first liver resections, 82 (68 %) R0, 13 (11 %) R1 and 25 (21 %) R2 excisions were possible. Median survival after first liver resection was 20 months; after R0 resection a median survival of 28 months and after R1/2 resection of 8 months was achieved. The 5-year survival rate was 16 % for the total group, 24 % in patients with R0 resection and 0 % for R1/2 resections. After a second liver resection (n = 14) there was a median survival of 28 months (5-year-survival-rate of 21 %) for all patients and of 41 months (5-year survival rate 38 %) after R0 resection. Morbidity and mortality after the first liver resection were 32.5 % and 5.8 %, respectively. In patients without extrahepatic tumor at the time of the first liver resection a median survival of 32 months (5-year survival rate 25 %) and 7 months was achieved after R0 resection and R1/2 resection, respectively. In case of extrahepatic tumor the median survival was 24 months (5-year survival rate 23 %) for R0 resection compared to 8 months after R1/2 resection. These data suggest that not the presence of extrahepatic tumor but rather the possibility of a R0 resection is most decisive for the prognosis after liver resection. We conclude that patients with liver metastases of non-colorectal, non-neuroendocrine tumors may benefit from liver resection. Similar to colorectal metastases, a second or third liver resection can be worthwhile in selected cases. Even in more unfavorable tumor entities, several cases of long-term survival were observed after surgical therapy. Therefore, the indication for liver resection should be considered carefully in every single case.Zusammenfassung. In einem Zeitraum von 11 Jahren wurden 140 Leberresektionen bei 127 Patienten (73 Frauen, 54 Männer; medianes Alter: 53 Jahre) wegen nichtcolorectaler nichtneuroendokriner Metastasen vorgenommen, darunter 120 Erst-, 14 Zweit- und 6 Drittresektionen. Bei den Primärtumoren handelte es sich um Mammacarcinome (n = 34), Leiomyosarkome (n = 20), Pankreascarcinome (n = 16), hypernephroide Carcinome (n = 13), Melanome (n = 9), Magencarcinome (n = 9), Bronchial- und Nebennierencarcinome (jeweils n = 6) sowie um 14 sonstige Tumoren. Extrahepatischer Tumorbefall (einschließlich synchroner Primärtumoren) bestand in 69 von 140 (49 %) Fällen, bei den 120 Erstresektionen lag in 51 % (n = 61) ein extrahepatischer Tumor vor. Von den 120 Erstresektionen wurden 82 (68 %) als R0-, 13 (11 %) als R1- und 25 (21 %) als R2-Resektionen eingestuft. Das mediane Überleben lag nach Erstresektion insgesamt bei 20 Monaten, nach R0-Resektionen bei 28 Monaten und nach R1/2-Resektionen bei 8 Monaten. Die entsprechenden 5-Jahres-Prognosen betrugen 16 % für alle Patienten und 24 % bzw. 0 % für Patienten mit R0- und R1/2-Resektionen. Nach Zweitresektion (n = 14) ergab sich ein medianes Überleben von 28 Monaten für alle Patienten und von 41 Monaten nach R0-Resektion. Die entsprechenden 5-Jahres-Prognosen lagen bei 21 % und 38 %. Die perioperative Morbidität lag nach der Erstresektion der Leber bei 32,5 %, die Letalität bei 5,8 %. Bei den Patienten ohne extrahepatischen Tumor zum Zeitpunkt der Erstresektion der Leber betrug das mediane Überleben nach R0-Resektion 32 Monate (5-Jahres-Prognose 25 %) und nach R1/2-Resektion 7 Monate. Im Vergleich hierzu lag das mediane Überleben nach R0-Resektion bei Patienten mit extrahepatischem Tumornachweis (Primärtumor und/oder sonstige Metastasen) bei 24 Monaten (5-Jahres-Prognose: 23 %) sowie nach R1/2-Resektion bei 8 Monaten. Entscheidend war also nicht so sehr, ob extrahepatische Tumormanifestationen vorlagen, sondern ob eine R0-Resektion möglich war. Die vorliegenden Ergebnisse zeigen, daß die Resektion auch nichtcolorectaler nichtneuroendokriner Lebermetastasen durchaus einen prognostischen Gewinn verspricht. Wie auch bei colorectalen Metastasen können Patienten mit hepatischen Rezidiven sogar von Zweit- oder Drittresektionen der Leber profitieren. In einigen Fällen konnten auch bei eher ungünstig eingeschätzter Ausgangssituation beeindruckende Langzeitverläufe beobachtet werden. Daher sollte die Indikation zur operativen Therapie in jedem Einzelfall überprüft werden.

Liver transplantation for hepatocellular carcinoma: clinical results and future aspects

SummaryThe treatment of unresectable hepatocellular carcinoma (HCC) by liver transplantation remains controversial. In our series, the 5-year survival value for 87 patients who underwent transplantations between 1972 and 1990 was 19.6%. There was no difference in the longterm survival of patients who had underlying cirrhosis and those who did not. In patients with early-stage tumours the long-term prognosis was improved, the 5-year survival in stage II disease being 55.6% according to UICC criteria. Even in some cases of more advanced tumour stage, good long-term results were obtained. In a review of the recent literature, we evaluated prognostic factors to work out criteria for a more differentiated indication for liver transplantation. Resection of increased radicality-which will keep its place as the therapy of choice — and transplantation should be performed complementarily. Further developments will reveal the value of multimodal therapeutic strategies, including chemo-embolisation, chemotherapy and immunotherapy.