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1.
J Cancer Res Clin Oncol ; 145(2): 445-455, 2019 Feb.
Article in English | MEDLINE | ID: mdl-30430229

ABSTRACT

INTRODUCTION: Patients (pts) with locally advanced (LAPC) or metastatic pancreatic ductal adenocarcinoma (mPDAC) have a dismal prognosis. Recently, new combination chemotherapies such as FOLFIRINOX and nab-paclitaxel/gemcitabine have demonstrated superiority over gemcitabine monotherapy. However, a substantial proportion of pts cannot tolerate these intensive front-line protocols. Moreover, the long-term superiority of multiagent protocols over less intensive strategies remains to be shown. To provide a benchmark for future studies, we analyzed the outcome of patients with LAPC or mPDAC treated at the West German Cancer Center before the FOLFIRINOX/nab-paclitaxel + gemcitabine era. METHODS: This retrospective analysis included 201 consecutive pts with LAPC and mPDAC treated between 2007 and 2011. Efficacy parameters were correlated with type of chemotherapy, number of treatment lines and clinicopathological parameters. RESULTS: Gemcitabine monotherapy was given as first-line therapy in 51.1%, whereas 48.9% received combination chemotherapies such as gemcitabine/oxaliplatin or FOLFOX. Patients received a median of two lines of treatment, with 54.8% receiving second-line and 37.9% receiving third- and further-line therapies. There was no significant difference between gemcitabine monotherapy and combination therapies. Despite moderate activity of first-line treatment, median overall survival for LAPC was 11.3 months and 8.7 months for mPDAC. Multivariate analysis identified age and number of treatment lines as prognostic markers. CONCLUSION: The long-term outcome of unselected pts with LAPC and mPDAC treated before the introduction of aggressive multiagent chemotherapy protocols compares favorably with the results of contemporary benchmark trials. This suggests a multifactorial benefit from interdisciplinary care provided over sequential treatment lines at high volume expert centers.


Subject(s)
Adenocarcinoma/mortality , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Pancreatic Ductal/mortality , Neoplasm Recurrence, Local/mortality , Pancreatic Neoplasms/mortality , Adenocarcinoma/drug therapy , Adenocarcinoma/secondary , Adult , Aged , Aged, 80 and over , Carcinoma, Pancreatic Ductal/drug therapy , Carcinoma, Pancreatic Ductal/secondary , Female , Follow-Up Studies , Humans , Lymphatic Metastasis , Male , Middle Aged , Neoplasm Invasiveness , Neoplasm Recurrence, Local/drug therapy , Neoplasm Recurrence, Local/pathology , Pancreatic Neoplasms/drug therapy , Pancreatic Neoplasms/pathology , Prognosis , Retrospective Studies , Survival Rate
2.
Clin Radiol ; 72(1): 95.e1-95.e8, 2017 Jan.
Article in English | MEDLINE | ID: mdl-27641945

ABSTRACT

AIM: To evaluate diffusion-weighted imaging (DWI) compared to standard magnetic resonance imaging (sMRI) in the assessment of inflammatory lesions of the small bowel. MATERIALS AND METHODS: Two readers retrospectively analysed MRI images of the small bowel including DWI followed by capsule endoscopy (CE) and ileocolonoscopy (ICS) in 30 consecutive patients with a suspected or established diagnosis of inflammatory bowel disease. Small bowel CE and the combination of CE + ICS were used as the standards of reference. Inflammatory lesions of the small bowel detected at endoscopy were compared with the findings of (1) sMRI alone (MRI without DWI), (2) DWI alone, and (3) sMRI in combination with DWI (sMRI + DWI). The sensitivity, specificity, and accuracy were calculated for all three readouts. The results of the three readouts were compared with each other. RESULTS: Using CE + ICS as the standard of reference, the mean sensitivity and specificity for the detection of inflammatory lesions of the small bowel at sMRI were 55.2% and 99.5%, at DWI 60% and 99%, and at sMRI + DWI 70% and 99%. Interobserver agreement between the two readers was very good (k=0.87-0.95). Two lesions in different patients were only detected at DWI. CONCLUSION: DWI of the small bowel not only allowed for the detection of inflammatory lesions with high accuracy, but also enabled the identification of additional lesions that were not found using sMRI alone.


Subject(s)
Diffusion Magnetic Resonance Imaging/methods , Image Interpretation, Computer-Assisted/methods , Inflammatory Bowel Diseases/diagnostic imaging , Intestine, Small/diagnostic imaging , Adolescent , Adult , Aged , Female , Humans , Image Enhancement/methods , Male , Middle Aged , Observer Variation , Reproducibility of Results , Sensitivity and Specificity , Young Adult
3.
Z Gastroenterol ; 54(12): 1296-1305, 2016 Dec.
Article in English | MEDLINE | ID: mdl-27936479

ABSTRACT

Background: Hepatocellular carcinoma (HCC) is one of the leading causes of death in cirrhotic patients worldwide. The detection rate for early stage HCC remains low despite screening programs. Thus, the majority of HCC cases are detected at advanced tumor stages with limited treatment options. To facilitate earlier diagnosis, this study aims to validate the added benefit of the combination of AFP, the novel biomarkers AFP-L3, DCP, and an associated novel diagnostic algorithm called GALAD. Material and methods: Between 2007 and 2008 and from 2010 to 2012, 285 patients newly diagnosed with HCC and 402 control patients suffering from chronic liver disease were enrolled. AFP, AFP-L3, and DCP were measured using the µTASWako i30 automated immunoanalyzer. The diagnostic performance of biomarkers was measured as single parameters and in a logistic regression model. Furthermore, a diagnostic algorithm (GALAD) based on gender, age, and the biomarkers mentioned above was validated. Results: AFP, AFP-L3, and DCP showed comparable sensitivities and specifities for HCC detection. The combination of all biomarkers had the highest sensitivity with decreased specificity. In contrast, utilization of the biomarker-based GALAD score resulted in a superior specificity of 93.3 % and sensitivity of 85.6 %. In the scenario of BCLC 0/A stage HCC, the GALAD algorithm provided the highest overall AUROC with 0.9242, which was superior to any other marker combination. Conclusions: We could demonstrate in our cohort the superior detection of early stage HCC with the combined use of the respective biomarkers and in particular GALAD even in AFP-negative tumors.


Subject(s)
Algorithms , Biomarkers, Tumor/metabolism , Carcinoma, Hepatocellular/metabolism , Carcinoma, Hepatocellular/pathology , Liver Neoplasms/metabolism , Liver Neoplasms/pathology , Age Distribution , Aged , Biomarkers/metabolism , Carcinoma, Hepatocellular/diagnosis , Female , Germany/epidemiology , Humans , Liver Neoplasms/diagnosis , Male , Middle Aged , Neoplasm Staging , Protein Precursors/metabolism , Prothrombin/metabolism , Reproducibility of Results , Sensitivity and Specificity , Sex Distribution , alpha-Fetoproteins/metabolism
4.
Z Gastroenterol ; 54(12): 1320-1326, 2016 Dec.
Article in English | MEDLINE | ID: mdl-27875848

ABSTRACT

Bleeding from esophageal varices is a major cause of mortality in patients with advanced liver disease. Although standard treatment and secondary prophylaxis are effective, in some patients sustained hemostasis cannot be achieved. We report the case of a woman with alcoholic liver disease in whom pharmacological, endoscopic, and intravascular therapies failed to control variceal bleeding. Only a combination of (repeated) band ligation, insertion of a self-expanding metal stent, TIPS implantation and redilatation, transjugular variceal embolization, and finally implantation of a portocaval shunt proved to be successful. We discuss the stepwise approach to this situation and the challenges encountered in the process.


Subject(s)
Angioplasty, Balloon/methods , Embolization, Therapeutic/methods , Esophageal and Gastric Varices/therapy , Gastrointestinal Hemorrhage/therapy , Portasystemic Shunt, Transjugular Intrahepatic/methods , Stents , Angioplasty, Balloon/instrumentation , Chronic Disease , Combined Modality Therapy/instrumentation , Combined Modality Therapy/methods , Esophageal and Gastric Varices/complications , Gastrointestinal Hemorrhage/diagnosis , Gastrointestinal Hemorrhage/etiology , Humans , Ligation/methods , Middle Aged , Portasystemic Shunt, Transjugular Intrahepatic/instrumentation , Recurrence , Treatment Outcome , Vascular Surgical Procedures/instrumentation , Vascular Surgical Procedures/methods
5.
Chirurg ; 87(6): 514-9, 2016 Jun.
Article in German | MEDLINE | ID: mdl-27090415

ABSTRACT

BACKGROUND: Perihilar cholangiocarcinoma (Klatskin tumor) is a rare tumor entity with an unfavorable prognosis despite optimal treatment. OBJECTIVES: The aim of the study is to investigate beneficial histopathological features and recommendations for surgery in perihilar cholangiocarcinoma to improve patients' long term survival. MATERIAL AND METHODS: 192 patients suffering from perihilar cholangiocarcinoma underwent attempted tumor resection between 1998 and 2008 at our clinic. 50 patients survived more than 2 years. The follow-up ended in December 2013. The resection type, the UICC stage and histopathological features were compared between three groups (2-3-year, 3-5-year and > 5-year survival groups). RESULTS: The overall 5­year survival rate of the study groups was 32 %, and even 16 % survived more than 10 years after surgery. Patients with lymph node positive tumors (p = 0.0126) and distant metastasis (p = 0.0376) had the poorest survival rate. Perineural invasion had no significant impact on the overall survival, but patients surviving more than 5 years had the lowest incidence of perineural invasion with 18.75 %. Caudate lobectomy was significantly (p = 0.011) associated with a survival of more than 5 years in our study. CONCLUSIONS: Complete tumor resection with additional caudate lobe resection is associated with long-term survival. Perineural invasion seems to be a negative prognostic factor for long-term survival.


Subject(s)
Bile Duct Neoplasms/mortality , Bile Duct Neoplasms/surgery , Klatskin Tumor/mortality , Klatskin Tumor/surgery , Adult , Aged , Bile Duct Neoplasms/pathology , Bile Ducts/pathology , Biopsy , Disease Progression , Female , Humans , Kaplan-Meier Estimate , Klatskin Tumor/pathology , Lymphatic Metastasis/pathology , Male , Middle Aged , Neoplasm Invasiveness , Neoplasm Staging , Prognosis
6.
Digestion ; 85(3): 185-91, 2012.
Article in English | MEDLINE | ID: mdl-22269340

ABSTRACT

BACKGROUND AND AIMS: Current treatment strategies of variceal bleeding (VB) include banding and sclerotherapy. However, up to 10% of bleeding events remain refractory to standard therapy with high mortality. With this study, we aimed to evaluate the implantation of self-expanding metal stents (SEMS) for the management of therapy-refractory variceal bleeding. PATIENTS AND METHODS: Eight cirrhotic patients who presented to our unit with a total of 9 refractory bleeding events were treated by SEMS placement. RESULTS: Stenting resulted in immediate hemostasis in all cases without recurrent bleeding with SEMS in situ. After stabilization, 1 patient was treated by transjugular intrahepatic portosystemic shunt (TIPS) and after the second bleeding episode by TIPS dilation. One patient underwent orthotopic liver transplantation (OLT). The remaining patients were treated with standard drug regimens to reduce portal pressure. The SEMS were removed after a median of 11 days. No acute hemorrhage was noted on stent retrieval. While no early rebleeding occurred in the patients after TIPS implant, TIPS dilation or OLT, 3 out of 5 patients on conservative treatment experienced recurrence of VB within 9 days after SEMS removal. CONCLUSIONS: SEMS placement sufficiently stops hemorrhage in refractory VB. Due to the high rebleeding rate after conservative treatment alone following SEMS removal, this procedure may be utilized as a mere bridging method. Additional interventional and/or surgical methods to effectively reduce portal pressure (i.e. TIPS, OLT) should be considered. Further studies to evaluate the optimum treatment algorithm of refractory esophageal VB are warranted.


Subject(s)
Esophageal and Gastric Varices/therapy , Gastrointestinal Hemorrhage/therapy , Liver Cirrhosis/complications , Stents , Adult , Aged , Endoscopy, Gastrointestinal , Esophageal and Gastric Varices/etiology , Esophageal and Gastric Varices/mortality , Female , Gastrointestinal Hemorrhage/etiology , Gastrointestinal Hemorrhage/mortality , Humans , Male , Middle Aged , Treatment Outcome
7.
Z Gastroenterol ; 49(8): 977-80, 2011 Aug.
Article in English | MEDLINE | ID: mdl-21811948

ABSTRACT

Hereditary spherocytosis is a common hemolytic anemia with an estimated incidence of 1 / 2500 births. It is caused by a molecular defect in one or more of the proteins of the red blood cell cytoskeleton. Mutations in the ABCB11 gene, encoding the bile salt export pump, can entail progressive familial intrahepatic cholestasis and benign recurred intrahepatic cholestasis. A 18 year old Turkish patient with hereditary spherocytosis was admitted to hospital with pruritus and severe jaundice. Ultrasound examination presented stones in gallbladder and bile duct. After endoscopic retrograde cholangiography with extraction of small bile duct stones abdominal pain resolved and liver enzymes normalized within a few days, but bilirubin and bile acids remained highly elevated. Liver biopsy revealed a severe canalicular cholestasis. Genetic analysis showed the compound heterozygous variants ABCB11 A 444V and 3084A > G. Treatment with ursodesoxycholic acid and intermittent therapy with prednisone reduced pruritus and jaundice with concomitant improvement of blood test. Here we report the first case of a patient with combined hereditary spherocytosis and compound heterozygous ABCB11 gene variants predisposing to intrahepatic cholestasis. Therefore, patients with hemolytic disorders should be investigated for bile acid transporter diseases in case of hyperbilirubinemia and severe cholestasis.


Subject(s)
ATP-Binding Cassette Transporters/genetics , Alleles , Bilirubin/blood , Cholestasis, Intrahepatic/blood , Cholestasis, Intrahepatic/genetics , Spherocytosis, Hereditary/blood , Spherocytosis, Hereditary/genetics , ATP Binding Cassette Transporter, Subfamily B, Member 11 , Adolescent , Anti-Inflammatory Agents/therapeutic use , Bile Acids and Salts/blood , Biopsy , Cholestasis, Intrahepatic/drug therapy , Cholestasis, Intrahepatic/pathology , DNA Mutational Analysis , Gallstones/blood , Gallstones/drug therapy , Gallstones/genetics , Gallstones/pathology , Genetic Carrier Screening , Genetic Variation/genetics , Humans , Liver/pathology , Male , Prednisone/therapeutic use , Protein Isoforms/genetics , Spherocytosis, Hereditary/drug therapy , Spherocytosis, Hereditary/pathology
8.
Clin Nephrol ; 75(1): 16-25, 2011 Jan.
Article in English | MEDLINE | ID: mdl-21176747

ABSTRACT

BACKGROUND: Among patients after renal transplantation (NTx), hepatitis C virus (HCV) infection is a risk factor for graft loss and patient death caused by hepatic decompensation. Also, HCV has been implicated in the pathogenesis of glomerular diseases in native and transplanted kidneys. Therefore, the aim of this retrospective cohort study was to determine the effects of the widely used calcineurin inhibitors (CNI) cyclosporine A (CsA) and tacrolimus (Tac) on hepatitis C virus replication, inflammatory activity, development of liver fibrosis, and long-term renal graft function. SUBJECTS AND METHODS: A cohort of 71 patients with HCV infection after kidney transplantation under immunosuppression with either CsA or Tac were analyzed for viral kinetics and serum transaminases. In addition, presence of liver fibrosis was detected by non-invasive measurements using the FibroScan. Graft function was determined biochemically. Patients with interferon therapy prior to transplantation were excluded from the study in order to avoid any impact of the antiviral therapy on outcomes. RESULTS: In the early period after transplantation, hepatitis C viral load was lower in patients treated with Tac as compared to CsA. This effect became negligible 3 months after transplantation. However, hepatic inflammatory activity was reduced in the CsA-treated group. Extent of liver fibrosis was similar in both groups of HCV-infected patients as well as in a control group of non-HCV-infected patients after renal transplantation (NTx), respectively. Renal function and glomerular filtration rate, as calculated by the modification of diet in renal disease (MDRD) formula, were significantly better in patients treated with Tac. CONCLUSIONS: During long-term immunosuppression, the CNIs cyclosporine A versus tacrolimus showed no significant differences in HCV-infected patients after renal transplantation with respect to viral replication and development of liver fibrosis. However, function of the renal graft is significantly better preserved in patients receiving tacrolimus.


Subject(s)
Cyclosporine/therapeutic use , Hepatitis C, Chronic/complications , Immunosuppressive Agents/therapeutic use , Kidney Diseases/surgery , Kidney Transplantation , Tacrolimus/therapeutic use , Adult , Aged , Calcineurin Inhibitors , Female , Germany , Graft Survival/drug effects , Hepacivirus/drug effects , Hepacivirus/genetics , Hepacivirus/growth & development , Hepatitis C, Chronic/diagnosis , Humans , Kidney Diseases/complications , Kidney Transplantation/adverse effects , Liver Cirrhosis/diagnosis , Liver Cirrhosis/virology , Liver Function Tests , Male , Middle Aged , RNA, Viral/blood , Retrospective Studies , Time Factors , Transaminases/blood , Treatment Outcome , Viral Load , Virus Replication
9.
Case Rep Gastroenterol ; 4(1): 57-65, 2010 Feb 06.
Article in English | MEDLINE | ID: mdl-21103229

ABSTRACT

The incidence of drug-induced acute liver failure is increasing. A number of drugs can inhibit mitochondrial functions, alter ß-oxidation and cause accumulation of free fatty acids within the hepatocytes. This may result in hepatic steatosis, cell death and liver injury. In our case, propofol, an anesthetic drug commonly used in adults and children, is suspected to have induced disturbance of the mitochondrial respiratory chain, which in consequence led to insufficient energy supply and finally liver failure. We report the case of a 35-year-old Caucasian woman with acute liver failure after anesthesia for stripping of varicose veins. Liver histology, imaging and laboratory data indicate drug-induced acute liver failure, presumably due to propofol. Hepatocyte death and microvesicular fatty degeneration of 90% of the liver parenchyma were observed before treatment with steroids. Six months later, a second biopsy was performed, which revealed only minimal steatosis and minimal periportal hepatitis. We suggest that propofol led to impaired fatty acid oxidation possibly due to a genetic susceptibility. This caused free fatty acid accumulation within hepatocytes, which presented as hepatocellular fatty degeneration and cell death. Large scale hepatocyte death was followed by impaired liver function and, consecutively, progressed to acute liver failure.

10.
Dtsch Med Wochenschr ; 135(42): 2076-80, 2010 Oct.
Article in German | MEDLINE | ID: mdl-20941681

ABSTRACT

HISTORY AND CLINICAL SYMPTOMS: A 58-year-old man was admitted to our hospital with acute chest pain and subfebrile temperatures. Two years ago, endovascular aortic stent-graft placement had been performed for acute type B aortic dissection complicated by malperfusion syndrome. DIAGNOSTIC ASSESSMENT: CT angiography showed a discrete soft-tissue attenuation mass between the aorta and esophagus. The patient developed progressive swallow disorder and esophago-gastro-duodenoscopy demonstrated deep esophageal ulcerations at the level of the implanted aortic stent-graft. Intravenous treatment with broad spectrum antibiotics was started. The FDG-PET/CT scan showed increased FDG uptake and air entrapment in the affected region establishing the diagnosis of aortoesophageal fistula formation. THERAPY AND OUTCOME: Given the generally poor condition of the patient and the high risk of any aggressive surgical intervention, a new limited surgical approach was chosen consisting of open transthoracic esophageal resection, blind closure of the stomach and cervical esophagostomy. A percutaneous endoscopic gastrostomy tube was placed. After three months, esophageal continuity was restored by retrosternal colon interposition. The presented therapeutic management resulted in a full recovery of the patient. CONCLUSION: Aortoesophageal fistula is a rare complication of thoracic aortic stent-graft placement. Patient may present with unspecific symptoms such as fever and rised inflammatory markers, but may also present with massive upper gastrointestinal bleeding. The herein presented limited therapy with esophageal resection represents a promising to the otherwise difficult therapy of aortoesophageal fistula.


Subject(s)
Angioplasty , Aortic Aneurysm, Thoracic/surgery , Aortic Diseases/diagnostic imaging , Aortic Dissection/surgery , Aortography , Blood Vessel Prosthesis Implantation , Esophageal Fistula/diagnostic imaging , Postoperative Complications/diagnostic imaging , Stents , Tomography, X-Ray Computed , Vascular Fistula/diagnostic imaging , Anastomosis, Surgical , Aortic Diseases/surgery , Colon/transplantation , Endoscopy, Digestive System , Esophageal Fistula/surgery , Esophagus/surgery , Humans , Image Processing, Computer-Assisted , Male , Mediastinitis/diagnostic imaging , Mediastinitis/surgery , Middle Aged , Positron-Emission Tomography , Postoperative Complications/surgery , Reoperation , Vascular Fistula/surgery
11.
Z Gastroenterol ; 47(8): 753-7, 2009 Aug.
Article in English | MEDLINE | ID: mdl-19662588

ABSTRACT

A 33-year old pregnant patient (pregnancy week 15) with a past medical history of ulcerative colitis with onset of the disease following the birth of her first child was admitted to the hospital with symptoms of weight loss, pyrexia, leukocytosis and bloody and mucous diarrhoea. Total ileocolonoscopy revealed an acute flare of ulcerative colitis. Within a few days, tender erythematous skin lesions occurred and were histologically proven to be neutrophilic dermatosis. Treatment with highly-dosed prednisone led to a complete remission of both cutaneous and intestinal manifestations. Both pathogenic entities are associated with similar immunological alterations, such as comparable cytokine and chemokine release patterns and recruitment of inflammatory cells. Recent data also indicates that proinflammatory cytokine levels are elevated in pregnancy, which might be pivotal in the pathogenesis and the severity of intestinal and extraintestinal symptoms. We present and discuss a diagnostic algorithm and an overall therapeutic rationale for Sweet's syndrome.


Subject(s)
Colitis, Ulcerative/diagnosis , Colitis, Ulcerative/therapy , Pregnancy Complications/diagnosis , Pregnancy Complications/therapy , Sweet Syndrome/diagnosis , Sweet Syndrome/therapy , Acute Disease , Adult , Female , Humans , Pregnancy , Treatment Outcome
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