Depression and Frailty in Patients With End-Stage Liver Disease Referred for Transplant Evaluation.

End-stage liver disease (ESLD) patients are believed to have a high prevalence of depression, although mental health in ESLD has not been studied comprehensively. Further, the relationship between depression and severity of liver disease is unclear. Using baseline data from a large prospective cohort study (N = 500) of frailty in ESLD patients, we studied the association of frailty with depression. Frailty was assessed with the five-component Fried Frailty Index. Patients were assigned a composite score of 0 to 5, with scores ≥3 considered frail. Depression was assessed using the 15-question Geriatric Depression Scale, with a threshold of ≥6 indicating depression; 43.2% of patients were frail and 39.4% of patients were depressed (median score 4, range 0-15). In multivariate analysis, frailty was significantly associated with depression (odds ratio 2.78, 95% confidence interval 1.87-4.15, p < 0.001), whereas model for ESLD score was not associated with depression. After covariate adjustment, depression prevalence was 3.6 times higher in the most-frail patients than the least-frail patients. In conclusion, depression is common in ESLD patients and is strongly associated with frailty but not with severity of liver disease. Transplant centers should address mental health issues and frailty; targeted interventions may lower the burden of mental illness in this population.

Prognostic impact of tumour-infiltrating immune cells on biliary tract cancer.

BACKGROUND: Biliary tract cancers (BTC) are relatively rare malignant tumours with poor prognosis. It is known from other solid neoplasms that antitumour inflammatory response has an impact on tumour behaviour and patient outcome. The aim of this study was to provide a comprehensive characterisation of antitumour inflammatory response in human BTC. METHODS: Tumour-infiltrating T lymphocytes (CD4+, CD8+, and Foxp3+), natural killer cells (perforin+), B lymphocytes (CD20+), macrophages (CD68+) as well as mast cells (CD117+) were assessed by immunohistochemistry in 375 BTC including extrahepatic (ECC; n=157), intrahepatic (ICC; n=149), and gallbladder (GBAC; n=69) adenocarcinomas. Overall and intraepithelial quantity of tumour-infiltrating immune cells was analysed. Data were correlated with clinicopathological variables and patient survival. RESULTS: The most prevalent inflammatory cell type in BTC was the T lymphocyte. Components of the adaptive immune response decreased, whereas innate immune response components increased significantly in the biliary intraepithelial neoplasia - primary carcinoma - metastasis sequence. BTC patients with intraepithelial tumour-infiltrating CD4+, CD8+, and Foxp3+ T lymphocytes showed a significantly longer overall survival. Number of total intraepithelial tumour-infiltrating Foxp3+ regulatory T lymphocytes (HR: 0.492, P=0.002) and CD4+ T lymphocytes (HR: 0.595, P=0.008) were tumour grade- and UICC-stage-independent prognosticators. The subtype-specific evaluation revealed that the tumour-infiltrating lymphocytic infiltrate is a positive outcome predictor in ECC and GBAC but not in ICC. CONCLUSION: Our findings characterise the immune response in cholangiocarcinogenesis and identify inflammatory cell types that influence the outcome of BTC patients. Further, we show that BTC subtypes show relevant differences with respect to density, quality of inflammation, and impact on patient survival.

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.

[Duodenal perforation after blunt abdominal trauma]. / Duodenalperforation nach abdominalem Trauma.

Duodenal perforation after a blunt abdominal trauma is a rare emergency situation that can result in life-threatening complications. We report on a woman who had a perforation of the duodenum after a supposed mild blunt abdominal trauma. Unremarkable at the initial presentation, the patient presented with acute abdominal pain and a retroperitoneal abscess five days after the initial trauma. The duodenal repair was performed with a Roux-Y anastomosis. Difficulties in diagnosis are very common, but the early recognition of the rupture is essential. The contrast-enhanced CT scan is the gold standard for diagnosis. Surgical management depends on the severity of the trauma and must be chosen on an individual basis.

[Histiocytosis of Langerhans cells. Simultaneous manifestation in both mastoid cavities]. / Langerhans-Zell-Histiozytose. Simultane Manifestation in beiden Mastoidhöhlen.

Histiocytosis X (Langerhans cells) is a rare disease with different forms of manifestation in the head and neck, which mostly occurs in children. We report the case of a 52-year-old male patient from Saudi Arabia who presented in the out-patient department of the University Hospital Charité Berlin with therapy-resistant otitis externa. ENT examination additionally showed nasal polyps. A paranasal computed tomography scan revealed as an incidental finding a mass forming tumor in both mastoids with osseous destruction of the posterior cranial fossa. Histological evaluation of the suspected tissue revealed histiocytosis X in both mastoids. After exclusion of a systemic disease local low-dose radiotherapy with 9 Gy (3x3 Gy) of the mastoid cavities was administered.

Radical surgery for right-sided klatskin tumor.

Local excision of hilar cholangiocarcinomas results in long-term survival in only very few cases. Therefore, the combination of right or left liver resection and bile duct resection has been the standard treatment since about 1990. Five-year survival rates after curative resection could be improved to 30-40%. Recurrence is frequently seen locally, therefore more extended resection with adherence to the surgical principals of tumor resection, such as the "no-touch technique", appears useful. Excellent results with 5-year survival rates up to 60% after curative resection can be achieved with right trisectionectomy together with principle en bloc hilar resection. Perioperative mortality is still high because of the small remaining liver volume.

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.

[The punctum plug as an option for treating retrograde air flow from the lacrimal sac]. / Der Punctum Plug als therapeutische Option des retrograden Aeroflows des Saccus lacrimalis.

BACKGROUND: The causes of keratoconjunctivitis sicca are multifarious. Major causes include eyelid anomalies, Sjögren's disease, injuries, radiation or mucin deficiency. In our case, nasal positive airway pressure due to muscular dystrophy is described as another possible cause. PATIENT: A 32-year-old male patient with advanced Duchenne muscular dystrophy requires nasal continuous positive airway pressure ventilation due to loss of the auxiliary respiratory muscles. The patient presented because permanent air flow from the lower right lacrimal point resulted in epiphora and keratoconjunctivitis sicca on the right side. THERAPY: We reversibly occluded the lower lacrimal duct with a punctum plug flow regulator. The lacrimal flow regulator is available in two sizes, 0.8 and 0.9 mm, and is designed to be inserted into the punctal aperture. The soft silicone plug is delivered with a disposable dilator and can be used on an outpatient basis. It is actually used for punctal occlusion in patients with chronic dry eye syndrome and regulates the flow of lacrimal fluid. After insertion of a 0.9 mm punctal plug, the patient reported marked improvement of the findings, which was confirmed in a follow-up after 4 and 8 weeks. On a visual analog scale of 1 to 10, the subjective status was given a rating of 8. CONCLUSION: By occluding the right lower lacrimal point with a punctal plug, we were able to markedly reduce the unpleasant retrograde air flow and the subjective complaints of the patient with nasal continuous positive airway pressure ventilation.

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.

[Results after lidloading with rigid gold weights--a meta-analysis]. / Ergebnisse nach Lidgewichtimplantation mit starren Goldgewichten--eine Metaanalyse.

INTRODUCTION: For the surgical therapy of lagophthalmos rigid gold implants were used. There are a lot of studies using rigid gold implants with widely different complications. In the primary study the small amount of patients is often a problem. The aim of our study was to survey the postoperative results and complications after insertion of rigid gold implants and to statistically compare the results with a meta-analysis. MATERIAL AND METHODS: 38 publications on 1000 rigid gold implants were analyzed in the context of a meta-analysis of the postoperative results. RESULTS: Complete lid closure can be obtained in 84.5 % with the rigid gold implants. The postoperative complication rates were 13.4 % for bulging, 6.4 % for migration, 6.8 % for extrusion, 11.5 % for corneal astigmatism and 7.0 % postoperative infections. DISCUSSION: Lidloading is a very simple and reversible procedure for the surgical treatment of lagophthalmos. The statistical analysis in using rigid gold implants showed a significant rate of postoperative complications. To increase the effectivity of the treatment method these results should be taken into account for alternative implants.

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.

Magnetic resonance imaging including magnetic resonance cholangiopancreatography for tumor localization and therapy planning in malignant hilar obstructions.

PURPOSE: To assess image quality and overall accuracy of magnetic resonance imaging (MRI), including two magnetic cholangiopancreatography (MRCP) techniques, for the diagnostics and preoperative work-up of malignant hilar obstructions. MATERIAL AND METHODS: Thirty-one patients with malignant hilar obstructions (hilar cholangiocarcinoma, n=30; hepatocellular carcinoma, n=1) received MRCP by two techniques (single-shot thick-slab and multisection thin-slice MRCP) and unenhanced and contrast material-enhanced MRI. MR assessment included the evaluation of image quality and visualization of bile ducts (5-point scale), and the classification of tumor status. MR results were subsequently correlated with the results from surgery and pathology. RESULTS: The maximum intensity projections of multisection thin-slice MRCP had significantly more artifacts compared to MRCP in the single-shot thick-slab technique, and overall image quality of single-shot thick-slab MRCP was rated significantly superior compared to multisection thin-slice MRCP (4.4 +/- 0.7 and 4.1 +/- 0.9, respectively). Moreover, ductal visualization of different parts of the biliary system was rated superior with single-shot thick-slab MRCP. In contrast, the original data from multisection thin slice MRCP facilitated visualization of periductal lesions and adjacent structures. Overall MR accuracy for the assessment of tumor status, periductal infiltration, and lymph node metastases was 90%, 87%, and 66%, respectively. CONCLUSION: For evaluation of malignant hilar obstructions, MRCP by the single-shot thick-slab technique had superior image quality and fewer artifacts; in contrast, besides sole biliary visualization, multisection MRCP depicted complementary adjacent parenchymal and periductal structures. We therefore recommend MRI, with a combination of both MRCP techniques, for the diagnostic work-up and therapy planning of malignant hilar obstructions.

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.

[Resection and reconstruction of the retrohepatic vena cava in combination with liver resections]. / Resektion und Rekonstruktion der retrohepatischen Vena cava in Kombination mit Leberresektionen.

Liver resection combined with the resection and reconstruction of the vena cava represents the only potential curative therapy for malignant hepatic tumors with invasion of the vena cava. We performed a liver resection with segmental replacement of the retrohepatic vena cava by synthetic grafts in 29 patients. In three cases, the additional presence of central involvement of all three hepatic veins required ex situ tumor resection. Four patients underwent a simultaneous exstirpation of the primary tumor (kidney or suprarenals). The remaining hepatic veins were reimplanted into the graft in three cases, and in two cases the renal veins were reimplanted. There was no perioperative mortality. A distal arteriovenous fistula was not applied. Five patients revealed postoperative transient liver insufficiency, requiring temporary dialysis in three cases. Two of these patients developed a transient multiorgan failure with the need of mechanical ventilation. 18 patients died during the course of follow-up, 17 of these cases due to recurrent metastases of the primary disease. Infection or thrombosis of the prosthetic vascular graft have not been observed. Beside tumor exstirpation, extended liver resection and concomitant vena cava replacement may prevent embolism as well as the obstruction of the vena cava with lower extremity swelling and the possibility of developing a Budd Chiari syndrome. We were able to achieve a long-term survival for surgically treated patients even in cases with advanced tumor stages.

Holographic face models as planning tool in maxillofacial surgery.

The holographic facial profile scan is a new technique for creation of high-resolution, three-dimensional, realistic facial computer models which can be used for surgical planning and documentation in maxillofacial surgery. First, a holographic image of the patient is recorded using a pulsed laser system. In a second step, called holographic tomography, the real image of the patient's hologram is reconstructed by means of a continuous-wave laser. By moving a screen through the real three-dimensional image, it is sliced into a series of two-dimensional projections which are captured with a digital camera. The slices containing the specific two-dimensional information are superimposed to a three-dimensional surface model using special software. The extremely short exposure time of 35 nanoseconds for taking a holographic image is separated from the time-consuming rendering process of the surface model; thus, the obtained models are not affected by the movements of the patient.