Secondary technical resectability of colorectal cancer liver metastases after chemotherapy with or without selective internal radiotherapy in the randomized SIRFLOX trial.

BACKGROUND: Secondary resection of initially unresectable colorectal cancer liver metastases (CRLM) can prolong survival. The added value of selective internal radiotherapy (SIRT) to downsize lesions for resection is not known. This study evaluated the change in technical resectability of CRLM with the addition of SIRT to FOLFOX-based chemotherapy. METHODS: Baseline and follow-up hepatic imaging of patients who received modified FOLFOX (mFOLFOX6: fluorouracil, leucovorin, oxaliplatin) chemotherapy with or without bevacizumab (control arm) versus mFOLFOX6 (with or without bevacizumab) plus SIRT using yttrium-90 resin microspheres (SIRT arm) in the phase III SIRFLOX trial were reviewed by three or five (of 14) expert hepatopancreatobiliary surgeons for resectability. Reviewers were blinded to one another, treatment assignment, extrahepatic disease status, and information on clinical and scanning time points. Technical resectability was defined as at least 60 per cent of reviewers (3 of 5, or 2 of 3) assessing a patient's liver metastases as surgically removable. RESULTS: Some 472 patients were evaluable (SIRT, 244; control, 228). There was no significant baseline difference in the proportion of technically resectable liver metastases between SIRT (29, 11·9 per cent) and control (25, 11·0 per cent) arms (P = 0·775). At follow-up, significantly more patients in both arms were deemed technically resectable compared with baseline: 159 of 472 (33·7 per cent) versus 54 of 472 (11·4 per cent) respectively (P = 0·001). More patients were resectable in the SIRT than in the control arm: 93 of 244 (38·1 per cent) versus 66 of 228 (28·9 per cent) respectively (P < 0·001). CONCLUSION: Adding SIRT to chemotherapy may improve the resectability of unresectable CRLM.

ANTECEDENTES: La resección secundaria de metástasis hepáticas de cáncer colorrectal (colorectal cancer liver metastases, CRLM) inicialmente irresecables puede prolongar la supervivencia. Se desconoce el valor añadido de la radioterapia interna selectiva (selective internal radiation therapy, SIRT). Este estudio evaluó el cambio en la resecabilidad técnica de las CRLM secundario a la adición de SIRT a una quimioterapia tipo FOLFOX. MÉTODOS: Las pruebas de radioimagen basales y durante el seguimiento de pacientes tratados con un régimen FOLFOX modificado (mFOLFOX6: fluorouracilo, leucovorina, oxaliplatino) ± bevacizumab (grupo control) versus mFOLFOX6 (± bevacizumab) más SIRT usando microesferas de resina de yttrium-90, en el ensayo de fase III SIRFLOX, fueron revisadas por 3-5 (de 14) cirujanos expertos hepatobiliares para determinar la resecabilidad. Los expertos efectuaron la revisión de forma ciega unos respecto a otros en relación con la asignación al tratamiento, estado de la enfermedad extra-hepática y situación clínica en el momento del estudio radiológico. La resecabilidad técnica se definió como ≥ 60% de revisores evaluando las metástasis del paciente como quirúrgicamente resecables. RESULTADOS: Fueron evaluables un total de 472 pacientes (control, n = 228; SIRT, n = 244). No hubo diferencias significativas basales en la proporción de metástasis hepáticas técnicamente resecables entre SIRT (29/244; 11,9%) y el grupo control (25/228; 11,0%: P = 0,775). Durante el seguimiento y en ambos brazos de tratamiento, un número significativamente mayor de pacientes se consideraron técnicamente resecables en comparación con la situación basal (54/472 (11,4%) basal y 159/472 (33,7%) al seguimiento). Hubo más pacientes resecables en el grupo SIRT que en el control (93/244 (38,1%) y 66/228 (28,9%); P < 0,001, respectivamente). CONCLUSIÓN: La adición de SIRT a la quimioterapia puede mejorar la resecabilidad de las CRLM irresecables.

Radioablation of adrenal gland malignomas with interstitial high-dose-rate brachytherapy : Efficacy and outcome.

PURPOSE: To assess the efficacy, safety, and outcome of image-guided high-dose-rate (HDR) brachytherapy in patients with adrenal gland metastases (AGM). MATERIALS AND METHODS: From January 2007 to April 2014, 37 patients (7 female, 30 male; mean age 66.8 years, range 41.5-82.5 years) with AGM from different primary tumors were treated with CT-guided HDR interstitial brachytherapy (iBT). Primary endpoint was local tumor control (LTC). Secondary endpoints were time to untreatable progression (TTUP), time to progression (TTP), overall survival (OS), and safety. In a secondary analysis, risk factors with an influence on survival were identified. RESULTS: The median biological equivalent dose (BED) was 37.4 Gy. Mean LTC after 12 months was 88%; after 24 months this was 74%. According to CTCAE criteria, one grade 3 adverse event occurred. Median OS after first diagnosis of AGM was 18.3 months. Median OS, TTUP, and TTP after iBT treatment were 11.4, 6.6, and 3.5 months, respectively. Uni- and multivariate Cox regression analyses revealed significant influences of synchronous disease, tumor diameter, and the total number of lesions on OS or TTUP or both. CONCLUSION: Image-guided HDR-iBT is safe and effective. Treatment- and primary tumor-independent features influenced survival of patients with AGM after HDR-iBR treatment.

[Papillary tumors - therapeutic concepts]. / Papillentumoren - therapeutische Konzepte.

Papillary tumors originate from the various structures of the ampulla of Vater; therefore, these rare tumors represent a heterogeneous group of tumor entities. Intestinal differentiated adenomas are the most common benign lesions, whereas intestinal differentiated papillary carcinomas are the most common malignant tumors. Carcinomas with pancreaticobiliary differentiation have a poorer prognosis. Mesenchymal and neuroendocrine tumors are among the least frequent papillary tumors. Diagnosis is performed by side-view upper endoscopy and biopsy. In cases of suspected malignancy a complete staging with computed tomography (CT) and endoscopic ultrasound scanning is indicated to determine local tumor spread.Adenomas are removed by endoscopic snare papillectomy whereas the therapy of choice for papillary carcinomas is pancreatic head resection with systematic lymphadenectomy. Patients with papillary carcinomas are most likely to benefit from adjuvant therapy, which should be determined in an interdisciplinary consensus conference considering the histological differentiation of the tumor.

[Biliary leaks after liver resection. Prevention and treatment]. / Gallenleckage nach Leberresektion. Vermeidung und Behandlung.

The surgical treatment of primary and secondary liver pathologies is nowadays standard practice. Since the first major resections performed by Langenbruch in 1888 there have been significant developments in the surgical technique. In addition to the surgical technique, the diagnostics and patient selection, perioperative care and anesthetic management as well as knowledge of liver anatomy and physiology have also shown significant developments. The proportion of complex operations, even within the framework of multimodal concepts has also increased. Despite this increasing complexity, the morbidity (< 45 %) and mortality (< 5 %) of liver surgery could be clearly reduced; however, the incidence of postoperative biliary leaks in large published series currently lies between 0 % and 30 % and has only shown a minimal reduction in recent years. The management of bile leakage requires an interdisciplinary management involving endoscopic and radiological, interventional or operative therapy. Most leakages (69-94 %) persist under conservative treatment (drainage and if necessary antibiotic therapy). For high volume fistulas and persistent biliary leakage endoscopic retrograde cholangiography (ERC) with stent placement represents the therapy of choice. Infections with biliary peritonitis and failure of interventional strategies often require revision surgery, possibly consisting of suturing if a leakage is identifiable, replacement of drainages or application of a bile duct drainage (e.g. T-drain or transhepatic external biliary drainage).

Liver resection for hepatocellular carcinoma in patients without cirrhosis.

BACKGROUND: Data on liver resection for hepatocellular carcinoma (HCC) without cirrhosis are sparse. The present study was conducted to evaluate the indications and results of liver resection for HCC with regard to safety and efficacy. METHODS: Data for patients who had liver resection for HCC without cirrhosis between January 1996 and March 2011 were retrieved retrospectively using a prospective database containing information on all patients who underwent hepatectomy for HCC. Patient and tumour characteristics were analysed for influence on overall and disease-free survival to identify prognostic factors by univariable and multivariable analysis. RESULTS: The 1-, 3- and 5-year overall survival rates after resection with curative intent for HCC without cirrhosis were 84, 66 and 50 per cent respectively. Disease-free survival rates were 69, 53 and 42 per cent respectively. The 90-day mortality rate was 4·5 per cent (5 of 110 patients). Surgical radicality and growth pattern of the tumour were independent prognostic factors for overall survival. Disease-free survival after resection with curative intent was independently affected by growth pattern and by the number and size of tumour nodules. CONCLUSION: Liver resection for HCC without cirrhosis carries a low perioperative risk and excellent long-term outcome if radical resection is achieved.

Liver transplantation to treat suspected hepatocellular carcinoma in iron-free foci in congenital hemochromatosis: case report.

Hepatocellular carcinoma (HCC) commonly develops in cirrhotic or noncirrhotic livers affected by congenital hemochromatosis. In patients with congenital hemochromatosis and HCC, liver transplantation is a therapeutic option with a 5-year posttransplantation survival rate as high as 80%. Herein is reported congenital hemochromatosis in a 37-year-old man. During a routine checkup, 2 liver nodules were detected. Signal characteristics at magnetic resonance imaging indicated the presence of iron-free foci (IFF). The serum α-fetoprotein concentration was within the range of normal, and repeated liver biopsy did not show histomorphologic signs of malignancy but confirmed the presence of IFF in surrounding siderosis. The patient was listed for liver transplantation with match MELD (Model of End-Stage Liver Disease including exceptions) because of suspected HCC. After 173 days on the waiting list, liver transplantation was performed successfully. Histologic examination of the explanted liver confirmed 2 HCC lesions with a diameter of 0.9 cm in the exact projection as the IFF detected at magnetic resonance imaging. At 20 months of rapamycin-based immunosuppression therapy, there were no signs of HCC recurrence. This is, to our knowledge, the first report of liver transplantation performed to treat suspected HCC based on the finding of IFF in congenital hemochromatosis, with histopathologic confirmation of the diagnosis of HCC after transplantation. According to this case and the current literature, IFF in patients with congenital hemochromatosis should be considered preneoplastic lesions vulnerable to possible development of HCC.

Acoustic radiation force impulse (ARFI) elastography in acute liver failure: necrosis mimics cirrhosis.

Acoustic radiation force Impulse (ARFI) technology correlates shear-wave velocity with fibrosis. It can differentiate between advanced fibrosis and normal tissue in chronic liver disease. However, specificity is impaired by cholestasis, inflammation or oedema in acute hepatitis. In patients with acute liver failure (ALF) necessitating liver transplantation ARFI has not been evaluated yet. We investigated 3 patients with ALF and compared their ARFI results to those of healthy controls (n = 33) and cases with liver cirrhosis (n = 21). In the 3 ALF patients shear-wave velocities were 3.0, 2.5, and 2.7 m/s, respectively. These results were significantly increased compared to those of healthy controls (median: 1.13 m/s; p < 0.001) and similar to those of cirrhotic individuals (median: 2.93 m/s). Two individuals underwent liver transplantation. Explants showed massive necrosis, but no signs of chronic liver disease. Patient 3 recovered spontaneously and showed decreasing ARFI results during follow-up. In conclusion, hepatic necrosis can mimic liver cirrhosis at ARFI evaluation in ALF patients and this impairs the specificity of ARFI.

Liver resection for metastatic gastric cancer.

AIMS: Liver resection represents a curative treatment approach in patients suffering from liver metastases from gastric cancer. However, its value in the treatment of these patients remains controversial. This study was conducted to evaluate the safety and effectiveness of liver resection in these conditions and to identify criteria for the selection of suitable patients. METHODS: From January 1988 to December 2002, 24 patients underwent liver resection for metastatic gastric cancer. The outcome of these 24 patients was retrospectively reviewed using a prospective database. Patient, tumour and operative parameters were analyzed for their influence on long-term survival. RESULTS: One patient died and four patients (17%) developed complications during the postoperative course. The overall one-, three- and five-year survival was 38%, 16% and 10%, respectively. After curative resection (n=17), the one-, three- and five-year survival rate was 53%, 22% and 15%, respectively, and patients with metachronous metastases restricted to the liver (n=5) had a one-, three- and five-year survival of 80%, 40% and 40%, respectively. In the univariate analysis, extrahepatic manifestation showed in tendency (p=0.069) and resection margins statistically significant (p=0.005) influence on survival. The multivariate analysis revealed only resection margins as an independent prognostic factor for survival. CONCLUSIONS: Long-term survival can be achieved by liver resection in well selected patients and may be considered in the multidisciplinary treatment approach of metastatic gastric cancer. Patients with metastatic disease restricted to the liver in whom a curative resection can be achieved seem to be most suitable for liver resection.

Radical surgery for hilar cholangiocarcinoma.

In the therapy of hilar cholangiocarcinoma, the most favorable survival rates over the long-term are achieved by a surgical concept involving a no-touch-technique, en-bloc-resection and wide tumor-free margins. Currently, these goals can be best achieved by our strategy to combine extended right hepatic resections and principle portal vein resection. In spite of extending resectability to patients with locally advanced tumors, formally curative resections could be performed in 80% of the patients. The 5-year survival rate in these patients is 61%. Liver transplantation had been abandoned by most centers in the 1980s due to poor overall results. Recently, a neoadjuvant strategy involving radiochemotherapy has been reported to result in excellent survival figures at least in a subset of patients suffering from cholangiocellular carcinoma arising in a primary sclerosing cholangitis (PSC). This protocol has been mainly proposed by the Mayo Clinic group and reached 5-year survival rates of 80% in those patients in whom it had been applicable. A substantial drop out rate from this neoadjuvant regimen due to tumor progression or treatment related complications is still a problem.

Liver resection for metastases from renal cell carcinoma.

BACKGROUND: This study was conducted to evaluate the safety and efficacy of liver resection in patients with hepatic metastases from renal cell carcinoma and to identify selection criteria for patients suitable for resection. METHODS: Between January 1988 and March 2006, 31 patients underwent liver resection for metastases from renal cell carcinoma. Patients were identified from a prospective database and retrospectively reviewed. Patient, tumor, and operative parameters were analyzed for their influence on long-term survival. RESULTS: The overall 1-, 3- and 5-year survival rates were 82.2%, 54.3%, and 38.9%, respectively. One patient was deceased and 4 developed complications during the postoperative course. In the univariate analysis, site of the primary tumor (P = 0.013), disease-free interval (P = 0.012), and resection margins (P = 0.008) showed significant influence on long-term survival. In the multivariate analysis, only the resection margins were identified as an independent prognostic factor after liver resection. CONCLUSIONS: Liver resection is effective and safe in the treatment of patients with hepatic metastases from renal cell carcinoma and offers the chance of long-term survival and cure. Achieving a margin-negative resection is the most important criterion in the selection of suitable patients for liver resection. However, the number of patients in the present study was small, and investigations of larger series may provide further prognostic parameters in these patients.

Extended resections of liver metastases from colorectal cancer.

BACKGROUND: Indications for resection of liver metastases from colorectal cancer and surgical strategies are still under debate. METHODS: We have retrospectively reviewed the outcome of 660 patients after 685 liver resections for metastases of colorectal cancer in our institution from 1988 to 2004. All surviving patients have a minimum follow-up period of 1 year. The longest follow-up in these patients is 16 years. Three different time periods of 5 to 6 years each were analyzed. RESULTS: The 30- and 60-day mortality rates were 1.5% (n = 10) and 2.2 % (n = 15), respectively. The rate of formally curative (R0) resections was 84%. Five-year survival rates in all patients and in patients after R0 resection were 37% and 42%, respectively. If only resections from 1999 to 2004 were considered, 5-year survival in patients after R0 resection was 50%. In a multivariate analysis, surgical radicality, ligamental lymph node involvement, number of liver metastases, and time period, in which the liver resection had been performed, were independent prognostic parameters. CONCLUSIONS: Outcome after liver resection for metastases from colorectal cancer has constantly improved. A formally curative resection is the most relevant prognostic parameter. Number of liver metastases and, in the few patients concerned, lymph node infiltration of the hepatoduodenal ligament, were further prognostic parameters.

Repeat liver resection for recurrent liver metastases from colorectal cancer.

AIMS: Numerous patients suffer from recurrence after resection of liver metastases from colorectal cancer. Recurrence is frequently restricted to the liver and repeat liver resection may offer a curative option in these patients. This study was conducted to clarify safety and effectiveness of this treatment and to identify prognostic factors of a favourable outcome after repeat hepatectomy. METHODS: Between January 1988 and March 2006 in our institution 811 patients underwent 841 liver resections for metastases from colorectal cancer. Among these, 94 patients underwent a repeat hepatectomy. Patients were identified from a prospective database and retrospectively reviewed. Results of different time periods were assessed and prognostic factors for a favourable outcome were determined. RESULTS: The perioperative morbidity and mortality was 24% (23 of 94) and 3% (3 of 94), respectively. The one-, three-, five- and ten-year survival for all patients in this series was 89%, 55%, 38% and 23%, respectively. In the univariate analysis, pT-stage of the primary, diameter of the largest metastases, surgical radicality, period of resection and distribution of metastases showed statistically significant influence on survival. The multivariate analysis revealed only pT-stage of the primary tumour, surgical radicality and period of resection as independent prognostic factors. CONCLUSIONS: Repeat hepatectomy is a safe and effective treatment for recurrent liver metastases from colorectal cancer. Perioperative risk and long-term survival were similar when compared to the results obtained during the initial resection. Achieving a curative resection is the most relevant prognostic factor for a favourable prognosis after repeat liver resection.

Diabetes mellitus is no independent risk factor for perioperative mortality following hepatic resection.

For patients with concomitant diabetes mellitus an increased perioperative mortality and morbidity in hepatic resections has repeatedly been described. Other studies, however, demonstrated equal outcome data in diabetic and non-diabetic patients. As patient populations were selected for underlying disease, conflicting results may reflect patient selection criteria rather than impact of diabetes mellitus on outcome measures. Therefore, a multivariate analysis in a largely unselected patient population has been performed to determine the independent prognostic value of diabetes mellitus in liver surgery. From a prospective database 633 adult patients undergoing hepatic resection without preceding major abdominal surgery or chemotherapy have been identified. Besides diabetes mellitus, demographic data, variables expressing the functional reserve of the liver, and parameters of surgical technique were analyzed for their impact on mortality and morbidity. 75 patients were diabetic (11.8 %) and 96 hepatic resections (15.2 %) were performed in cirrhotic patients. In the univariate analysis, concomitant diabetes was associated with an increased mortality compared to all non-diabetic patients (10.7 % vs. 5.3 %, p = 0.047). Diabetic patients, however, were also significantly older and presented a higher prevalence of liver cirrhosis. Multivariate modeling finally identified only age, albumin, cirrhosis, extent of surgery, and era of surgery as independent variables with an impact on perioperative mortality. Overall, complications were detected in diabetic and non-diabetic patients with a comparable frequency (44 % vs. 36 %, p = 0.179). Also, the length of in-hospital stay did not significantly differ between both groups (18.5 +/- 1.7 vs. 17.7 +/- 1.0 days, p = 0.119). Rates of postoperative renal impairment, prolonged ascites or pneumonia, however, were higher in diabetics than in other patients. Following established cardiopulmonary and surgical selection criteria, diabetes mellitus is not an independent risk-factor for perioperative mortality in hepatic resections. Although the overall postoperative morbidity was not different in diabetic and non-diabetic patients, a specific pattern of complications has been identified, mandating particular attention in the postoperative course of diabetic patients.

Liver transplantation for hepatocellular carcinoma in cirrhosis: prognostic parameters.

Selection of patients suffering from hepatocellular carcinoma (HCC) in cirrhosis for liver transplantation is based upon the number and diameter of tumor nodules but not with vascular invasion. From 1989 to 2003, 1619 liver transplantations were performed in 1471 patients, including 163 patients with an HCC in cirrhosis. Selection criteria were a maximal diameter of up to 5 cm when the tumor appeared to be uninodular, or up to 3 cm in the case of two or three nodules and no vascular invasion prior to transplantation. The postoperative mortality rate was 1.7%. One-, 5- and 10-year survivals were 88%, 62%, and 51%, respectively. Among 1307 transplantations without HCC, the rates were 90%, 84%, and 76%, respectively (P < .0001). Multivariate analysis identified histopathological grading and vascular invasion to predict survival. A subgroup analysis showed 5-year survivals of 67% and 57% for well versus moderately differentiated tumors with vascular invasion. Liver transplantation is a safe and effective long-term treatment for small HCC in cirrhosis. Exeptions from the morphometric rules may be justified for patients with HCC in cirrhosis who show well or moderately differentiated tumors with vascular invasion.