PubMed Health⌕ Search

Biomedical subjects

H Lobeck

Publications and source records attributed to H Lobeck.

At least 19 recordsLinked to original sources

[Prolonged remission after immunotherapy of a previously refractory peripheral T-cell non-Hodgkin lymphoma].

HISTORY AND ADMISSION FINDINGS: A 54-year-old woman in good condition was admitted because of a rapidly growing tumor in the right groin with skin infiltration. There were no B-symptoms and no increased susceptibility to infections. INVESTIGATIONS: Histology revealed a peripheral T cell non-Hodgkin lymphoma (NHL). Laboratory tests showed borderline elevation of lactate dehydrogenase. Staging computed tomography (CT) revealed widespread moderately enlarged lymph nodes and the main lesion in right groin measuring 5 x 6 cm which was classified as stage IIIAE. TREATMENT AND COURSE: According to the phase-II-trial DSHNHL-2003 - 1 (German study group for high grade NHL) the patient was scheduled for cycles of CHOEP at 14-day intervals plus granulocyte colony stimulating factor. During the first cycle she developed a worsening wound infection and an infection of her port catheter. Because response to treatment was only minimal a biopsy was performed which showed persisting malignant lymphoma. As a result she was not given the 4-weekly addition of alemtuzumab, as provides in the study protocol. Instead she received alemtuzumab subcutaneously for eight weeks at a dose of 3 x 30 mg/week plus prophylactic antibiotics. A good partial response was obtained, followed by radiotherapy with 36 Gy to the main lesion in the right groin. The follow up CT-scans one year after treatment showed a stable remission. CONCLUSION: In T-NHL with primary non-response it is especially difficult to induce a stable remission. Despite a course which was complicated by infections and a failing response to increased chemotherapy a remission was achieved in this patient with a monotherapy of alemtuzumab for eight weeks without complications, followed by radiotherapy.

Alemtuzumab↗

Severe panarteritis associated with drug abuse.

A case of panarteritis with purpura fulminans, mononeuritis multiplex, gastrointestinal manifestation and presumably cardiac involvement in a previously healthy 22-year-old man with a history of drug abuse including cocaine, cannabinoids and methamphetamines is described. Histopathological examination of the gut led to the diagnosis of panarteritis without immune deposits. Antineutrophil antibodies were negative. Besides the drugs, no other possible cause of vasculitis was found. The patient recovered completely after 1 year. Drug abuse is a thus possible cause of severe extracerebral disabling vasculitis.

Acute Disease↗

Extended resections for hilar cholangiocarcinoma.

OBJECTIVE: To evaluate different strategies for extended resections of hilar cholangiocarcinomas on radicality and survival. SUMMARY BACKGROUND DATA: Surgical resection of hilar cholangiocarcinoma is the only potentially curative treatment. Resection of central bile duct carcinomas, however, cannot always comply with the general principles of surgical oncology to achieve wide tumor-free margins with no-touch techniques. METHODS: From 1988 to 1998, 95 patients underwent resection of hilar cholangiocarcinoma. Eighty patients had hilar and hepatic resections and 15 had liver transplantation and partial pancreatoduodenectomy (LTPP; i.e., eradication of the entire biliary tract using a no-touch technique). RESULTS: The 60-day death rate was 8%. The overall 1- and 5-year survival rates were 67% and 22%, respectively. Five-year survival rates after R0, R1, and R2 resections were 37%, 9%, and 0%. In a multivariate analysis, surgical radicality was the strongest determinant of survival (p < 0.001). The rate of formally curative resection (R0 resection) was significantly lower in hilar resections (29%) than in liver resections (left hemihepatectomy 59%, right hemihepatectomy 55%, right trisegmentectomy 65%; p < 0.05). The highest rate of R0 resection was observed after LTPP (93%; p < 0.05). Right trisegmentectomies achieved the highest rate of 5-year survival after R0 resection (57%). In a multivariate analysis of patient survival after R0 resection, additional portal vein resection was the only significant factor. The 5-year survival rate after formally curative liver resection with portal vein resection was 65% versus 28% without. CONCLUSION: Extended resections, especially right trisegmentectomies and LTPP, resulted in the highest rate of R0 resection. Right trisegmentectomy together with portal vein resection best represents the principles of surgical oncology and may be regarded as the surgical procedure of choice. Immunosuppression limits the applicability of LTPP.

Aged↗

Pretransplant virological markers hepatitis C virus genotype and viremia level are not helpful in predicting individual outcome after orthotopic liver transplantation.

BACKGROUND: Recurrence of hepatitis C viremia after orthotopic liver transplantation (OLT) is nearly universal, leading to variable outcome from no to severe recurrent disease. In the present study, the prognostic relevance of hepatitis C virus (HCV) genotypes and viremia for the development and severity of graft hepatitis was investigated. METHODS: A total of 79 patients with chronic hepatitis C who could be followed for 1 to 78 months (mean: 30 months) after OLT were included in this study. HCV RNA concentrations were measured before OLT, 1 month after OLT, as well as in the long-term follow-up after OLT in 54 of the 79 patients. RESULTS: Graft hepatitis could be documented in 40 of the 79 patients (51%), and 7 of them (9%) progressed to liver cirrhosis. More severe forms of graft hepatitis predominated in patients with subtype 1b infection, and all seven patients with progression to liver cirrhosis had subtype 1b (P=NS). Neither the pretransplant nor the posttransplant HCV RNA levels were significantly associated with the occurrence of graft hepatitis. However, there was a trend of more severe recurrent disease in subtype 1b-infected patients with high level viremia in the early course after OLT. CONCLUSIONS: Pretransplant HCV virological markers are not helpful to predict the outcome after OLT. However, it should be further investigated whether estimation of HCV genotype and viremia levels very early after OLT, i.e., within the first weeks, may be a better approach to recognize high-risk patients.

Adult↗

The extracellular matrix: an early target of preservation/reperfusion injury and acute rejection after small bowel transplantation.

BACKGROUND: Endothelial cells are known to be an early target of preservation/reperfusion injury and acute rejection, whereas the extracellular matrix (ECM) may also play an equally important role in the sequelae of both events. METHODS: Syngeneic and allogeneic rat small bowel transplantations (SBTX) were performed after 6 hr of preservation. Animals were subsequently killed at defined time points for determination of ECM parameters within the graft and in plasma. RESULTS: Laminin levels were significantly increased 20 min after reperfusion (syngeneic SBTX: 357+/-65.9 ng/ml; allogeneic SBTX: 361+/-79.6 ng/ml; P< or =0.01). After syngeneic transplantation, laminin levels normalized by postoperative day (POD) 7, whereas there was a rejection-induced increase after allogeneic SBTX (POD 7: 179+/-60.1 ng/ml; POD 9: 333+/-13.6 ng/ml; P< or =0.01 vs. syngeneic SBTX). This increase was accompanied by an increase in tumor necrosis factor-alpha levels at POD 9. Hyaluronic acid levels were significantly elevated after 24 hr (syngeneic SBTX: 1086+/-176 microg/L; allogeneic SBTX: 918+/-108 microg/L; P< or =0.01). After syngeneic SBTX, hyaluronic acid levels normalized by POD 7, whereas persistently higher levels were observed after allogeneic SBTX. Immunohistochemistry confirmed early changes (20 min after reperfusion) at the ECM. Anti-laminin and anti-CD44 staining normalized at POD 5 after syngeneic SBTX. After allogeneic SBTX, rejection-specific changes were evident with anti-laminin staining commencing on POD 5 and progressing until POD 9. At similar time points, increased expression of fibronectin- and interferon-gamma-positive material was evident. CONCLUSIONS: The ECM can be considered to be an early target of preservation/reperfusion injury and acute rejection. Plasma parameters reliably reflected the changes observed within the graft. Laminin and hyaluronic acid levels may be used as indicators of initial graft function. Furthermore, the increase in laminin levels was an early indicator of acute rejection. Determination of these parameters may significantly improve monitoring after SBTX.

Animals↗

[Myoepithelial carcinoma (malignant myoepithelioma) of the salivary glands. A case report].

We report the rare development of a myoepithelial carcinoma in a pleomorphic adenoma involving the minor salivary glands in the buccal mucosa of a 78-year-old female. Tumor presented as a small asymptomatic left buccal mass. The initial dominant component of the neoplasm was a pleomorphic adenoma, while the minor component was a myoepithelial carcinoma. Recurrences of tumor after 2 and then 5 years were excised. Histopathological examination of the last tissue removed showed a pure myoepithelial carcinoma of the minor salivary glands without evidence for a pleomorphic adenoma. The clinical features, therapy, diagnosis, histopathology and literature are reviewed.

Adenoma, Pleomorphic↗

Effective therapy for hepatic M. Osler with systemic hypercirculation by ligation of the hepatic artery and subsequent liver transplantation.

Hereditary hemorrhagic teleangiectasia, or M. Osler (Osler-Weber-Rendu disease), is an autosomal dominant, systemic fibrovascular dysplasia. This may lead to increased liver blood flow from arteriovenous fistulas. A 45-year-old woman with a known M. Osler was admitted for liver transplantation. On admission, exertional dyspnea was the predominant symptom. Radiological investigations revealed multiple intrahepatic arteriovenous fistulas and consecutive high-output heart failure. Laboratory findings revealed remarkably elevated bilirubin and alkaline phosphatase. To alleviate the high-output cardiac failure, the hepatic artery was ligated. Fourteen months later, the patient presented again with increased levels of bilirubin and recurrent bleeding episodes from esophageal varices grade IV. The patient underwent liver transplantation and post-transplant recovery was excellent. A hyperdynamic circulatory state due to a hepatic M. Osler has been treated in several cases by ligation or embolization of the hepatic artery. This procedure, however, is recommended only for patients with normal liver function and carries a considerably risk of bile duct necrosis.

Cardiac Output↗

Recurrence-free survival after liver transplantation for small hepatocellular carcinoma.

Recurrence-free survival (RFS) in patients with small hepatocellular carcinoma (HCC) after orthotopic liver transplantation (OLT) was analyzed. From 1988 until 1996, 725 OLTs were performed in 669 patients. In 52 adults, HCC was confirmed histologically. OLT was limited to patients with small (< 5 cm) HCC with a maximum number of three nodules. Actuarial survival for these 52 patients at 1 and 5 years is 88% and 71%. RFS was defined as time until death without recurrence time until follow up with a diagnosis of recurrence, or, in patients without recurrence, time of last follow up. Overall, the 5-year RFS was 60%. Five-year RFS was less for bilobar compared to unilobar tumors (36% vs 70%), less for stage IVa tumors (UICC) compared to stage I-III tumors (17% vs 71%), and less for multiple compared to solitary tumors (54% vs 67%). In conclusion, potential cure may be achieved in more than 50% of all transplanted patients.

Actuarial Analysis↗

Searching for the optimal management of hepatitis C patients after liver transplantation.

The optimal immunosuppressive regimen in patients transplanted for hepatitis C (HCV) is still under discussion. High immunosuppression may promote viral replication and recurrent graft hepatitis. But acute and chronic rejection frequently seen in conjunction with HCV recurrence may require some rescue therapy. One hundred and thirty-seven patients transplanted for HCV cirrhosis, who were HCV-RNA positive prior to transplantation, were analyzed. Seventy-nine patients received CSA-based immunosuppression and 58 patients FK506-based immunosuppression. One-month patient survival was 100% in both groups. Three month and 1-year survival rates and the cumulative 1-5-year patient survival was similar in CsA-treated [67/79 (84.8%)] and FK506-treated patients [50/58 (86.2%)]. Retransplantations for HCV recurrence were performed in 5.1% of CsA-treated patients and 6.9% of FK506-treated patients; it was successful in 50% and 75% of patients, respectively. Conversion from CsA to FK506 and vice versa was high with 25 out of 79 patients (31.6%) converting in the CsA group and 8 out of 58 patients (13.8%) converting in the FK506 group. Conversion to FK506 was performed due to acute and chronic rejection and to CsA because of toxicity and HCV recurrence. In both groups, 25% of converted patients died. Five patients of the CsA group and 9 of the FK506 group received OKT3; more than one-third of each group died. Five patients in the CsA group and 6 in the FK506 group received mycophenolate mofetil (MMF) for HCV recurrence or acute and chronic rejection in conjunction with HCV recurrence. All patients of this critical group are alive with good graft function. In conclusion, survival rates of HCV patients were similar to those seen for other indications. Conversion from CsA to FK506 and vice versa was high and reflects a critical group concerning patient survival. OKT3 treatment should be avoided. A promising therapeutic option for critical patients experiencing acute or chronic rejection in conjunction with HCV recurrence may be treatment with MMF.

Hepatitis C↗

Changes at the extracellular matrix during acute and chronic rejection in human liver transplantation.

We have previously observed changes at the extracellular matrix (ECM) which significantly correlated with the extent of preservation and reperfusion injury. In the present study, we attempted to investigate whether the ECM may be also involved in the pathophysiological sequelae of acute and chronic rejection. Of 81 patients monitored for the ECM parameters laminin, hyaluronic acid, fibronectin receptor, and transforming growth factor (TGF)-beta, 28 patients developed acute rejection (< 1 month), in 14 patients (17.4%) acute rejection was steroid resistant, 4 patients (4.5%) developed early chronic rejection following acute steroid-resistant rejection. Acute and chronic rejection were confirmed by established clinical and histological criteria. Laminin levels were significantly increased in patients experiencing acute steroid-resistant rejection (4204 +/- 133 ng/ml; P < or = 0.01) compared with patients with steroid-sensitive rejection (1059 +/- 27.3 ng/ ml) and with an uneventful postoperative course (1214 +/- 17.4 ng/ml). No increase in laminin was observed in those four patients who developed early chronic rejection (1099 +/- 58.7 ng/ml). Hyaluronic acid, fibronectin receptor, and TGF-beta levels also increased in patients with acute steroid-resistant rejection; hyaluronic acid: 290 +/- 10.8 micrograms/l vs 154 +/- 13.6 micrograms/l and 131 +/- 11.7 micrograms/l in patients with steroid-sensitive and no rejection, respectively; fibronectin receptor: 1003 +/- 23.5 ng/ml vs 573 +/- 24.8 ng/ml and 428 +/- 13.6 ng/ ml in patients with steroid-sensitive and no rejection, respectively; and TGF-beta: 393 +/- 14.9 pg/ml versus 315 +/- 10.7 pg/ml and 233 +/- 8.9 pg/ml in patients with steroid-sensitive and no rejection, respectively. A further increase in hyaluronic acid levels was observed in patients who developed early chronic rejection, while fibronectin receptor and TGF-beta levels remained low, similarly to laminin levels. The increase in laminin, hyaluronic acid, fibronectin receptor, and TGF-beta during acute steroid-resistant rejection may be stimulated by the rejection-related release of cytokines and adhesion molecules which paralleled the increase in ECM parameters. The lack of increase in laminin and fibronectin receptor levels in those patients who developed early chronic rejection may reflect an inability to recover from acute rejection.

Acute Disease↗