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Biomedical subjects

H J Gassel

Publications and source records attributed to H J Gassel.

At least 19 recordsLinked to original sources

[Therapeutically options for primary and secondary hepatic malignancies].

Therapeutically options for the treatment of patients with primary hepatic malignancies have grown in recent years. Apart from liver resection and organ transplantation, representing the only curative strategies for primary hepatic malignancies, a variety of palliative procedures have been introduced. Some of these result in extended patient survival. However, the combination of a malignant disease and an irreversible organ damage remains to be the main problem in the majority of patients with primary liver Cancer. Liver resection is the only curative therapy for patients with isolated hepatic colorectal metastases and can be performed with low morbidity and mortality if a correct indication and a standardized procedure is applied. In case of intrahepatic tumour recurrence re-resection is indicated as long as extrahepatic metastases can be excluded. In patients with primary unresectable metastases a downstaging-chemotherapy, two-stage hepatectomy or portal vene embolization might result in a secondary respectability. Locally ablative procedures are being evaluated at present, in the palliative Situation survival can be prolonged. In the future multimodal therapeutic approaches will dominate the treatment of primary and secondary hepatic malignancies.

Colorectal Neoplasms↗

Endometrial carcinoma recurrence in an abdominal scar 14 years after total hysterectomy.

BACKGROUND: Abdominal scar recurrence of endometrial carcinoma after hysterectomy has been only occasionally described and occurred mostly within 5 years after surgery. Direct tumor cell seeding in the abdominal wound at the time of operation is thought to be most likely the cause of recurrence. CASE: The patient underwent total abdominal hysterectomy for early stage endometrial carcinoma. She presented 14 years later with an abdominal scar recurrence that was radically resected. Histology of the tumor was similar to that of the primary carcinoma. CONCLUSION: Recurrences of endometrial carcinoma in an abdominal scar can occur even many years after hysterectomy and the concept of dormant cancer tumor cells is discussed as cause of recurrence rather than direct tumor cell implantation at the time of operation.

Abdomen↗

[Primary glomangioma of the liver. A new differential benign liver tumor diagnosis].

Glomus organs are arteriovenous anastomoses which control the thermoregulation of the extremities. Benign tumors of these glomus organs, termed "glomangiomas", are therefore most frequently located in the fingers and toes. Case reports of primary glomangiomas in the respiratory- and gastrointestinal tracts as well as in the genital organs have been published. On the other hand, glomus tumors of the liver have not yet been described. We report the case of a 61-year-old patient with a smooth subcapsular lesion within the liver detected by a routine ultrasound scan. Further diagnostic imaging did not match with one of the common liver tumors. The diagnosis of a glomangioma was finally made by liver biopsy and subsequent histology. A review of the literature revealed a potential transformation of glomangiomas. Since the patient reported on inappetence weight loss and the tumor showed growth tendency, the indication for surgical excision was made. Final histologic investigation revealed no signs of malignancy. The primary glomangioma of the liver is a new differential diagnosis of benign liver tumors. As there is a possibility of malignant degeneration, we propose the decision for surgical removal once there are clinical symptoms and a growth tendency of the lesion.

Diagnosis, Differential↗

Surgical management of prosthetic vascular graft infection: comparative retrospective analysis of 30 consecutive cases.

BACKGROUND: Graft infection after vascular prosthetic reconstruction for the treatment of peripheral arterial occlusive disease (PAOD) is a rare but severe complication with poor outcome. The options for surgical treatment are not uniformly accepted and remain controversial. PATIENTS AND METHODS: We retrospectively analyzed the histories of 30 patients treated for prosthetic graft infection (Szilagyi grade III) in our hospital between 1994 and 1999 to determine which forms of treatment were best suited for which types of patient. In the majority of cases the initial treatment was lower-extremity bypass surgery. The most frequent location of infection was the groin (73%). Staphylococci (13% of which were methicillin resistant) were the most common type of bacteria. The overall incidence of prosthetic infection was 2.3%. RESULTS: After confirmation of the infection by computed tomography (CT) or white blood cell scintigraphy, one of the following 5 forms of surgical treatment was performed: 1. Removal of the infected prosthesis and its simultaneous replacement by an autologous vein bypass. 2. Bypass removal and secondary replacement by an autologous vein. 3. Extra-anatomical replacement. 4. Graft removal and primary amputation. 5. Local therapy with debridement and secondary wound healing. In some patients primary amputation after graft infection was necessary to prevent further deterioration with fulminant sepsis. The overall mortality was 17%, the amputation rate was 60%. CONCLUSIONS: The best results were achieved by early complete removal of the alloplastic material and one-step replacement by either an autologous vein or extra-anatomic bypass. This resulted in a limb salvage rate of 54% and 40% and mortality rates of 9% and 0%, respectively.

Aged↗

[Endovascular therapy in combination with conventional vascular surgery for the treatment of peripheral arterial obliterative disease].

INTRODUCTION: In a prospective trial we analysed the results and the management of complications following a combined endovascular and vascular surgical therapy of peripheral occlusive arterial disease (POAD). PATIENTS AND METHODS: From November 1998 until January 2001 a total number of 61 patients with 64 extremities were included in this study. By preoperative angiography 19 patients had stenoses at three levels, 42 patients suffered from stenoses at two levels. The iliac axis was recanalized by intraluminal angioplasty (ITA) plus stent placement under general anesthesia. Simultaneously an infrainguinal bypass reconstruction and a local thrombendarterectomy (TEA) rsp. were performed. Intra- and postoperative complications and the patency rates as assessed by colour doppler ultrasound and angiography were analysed. RESULTS: The rate of conversion from endovascular to conventional surgery was 12.5 %. In 56 cases the endovascular therapy of the iliac axis was successful. In 28 patients a distal bypass was implanted, in 25 patients a local TEA was performed. Intraoperatively 6 dissections (10.7 %) were noted, dislocation of stents were seen in 4 patients (7.1 %), perforations occurred in 2 patients (3.6 %). Both perforations and 5/6 dissections were detected intraoperatively and were treated by endovascular means without complications. The early postoperative patency rate was 98.2 %, the secondary patency rate was 100 % and the cumulative patency rate after two years was 98.2 %. DISCUSSION: ITA and stent placement in the iliac axis can be established quickly and safely by the vascular surgeon. Intraoperative complications can be managed by endovascular means in most cases. Stent dislocation is avoidable in most cases. The complication rate after such combined endovascular therapy and conventional vascular surgery is determined by the surgical but not the endovascular part. Excellent early results and low complication rates lead to the conclusion that endovascular therapy in combination with conventional vascular surgery seems to be a reasonable supplement to the therapeutic options for the treatment of POAD.

Aged↗

Presentation of an unusual benign liver tumor: primary hepatic glomangioma.

Glomus organs are small arteriovenous anastomoses chiefly responsible for thermoregulation of the distal portion of the extremities. Glomangiomas are benign tumors of these bodies. They occur preferentially in the fingers and toes, but some case reports describe primary glomangiomas in the respiratory or gastrointestinal tract and genitals. To date, no glomangiomas of the liver have been reported. We report on a 61-year-old patient in whom routine ultrasound disclosed a subcapsular well-defined mass in the liver. Further imaging showed that the mass did not correspond to any of the usual liver tumors. Biopsy finally revealed it to be a primary glomangioma of the liver. Clinically, there was lack of appetite and weight loss over a period of several months. Owing to the possibility of malignant transformation of glomangiomas, as described in the literature, the tumor was excised under existing clinical symptoms and continued slow growth. Further histological evaluation of the tumor did not reveal malignancy. Primary glomangioma of the liver is a new differential diagnosis for benign liver neoplasms. Because there is a potential for malignant transformation, the existence of clinical symptoms and continuing growth are indications for resection.

Glomus Tumor↗

Persistence of stable intragraft cell chimerism in rat liver allografts after drug-induced tolerance.

BACKGROUND: Drug-induced tolerance of rat liver allografts is well documented. We analyzed cellular events during immunosuppressive therapy on day (d) 10 and in the late phase (d 100) after transplantation to assess for characteristics in the intrahepatic leukocyte (IHL) population in the phase of tolerance. METHODS: Lewis rats served as recipients of Dark Agouti rat livers. Temporary immunosuppression with either cyclosporine (CsA) monotherapy (3 mg/kg/d) or triple therapy that consisted of a subtherapeutic CsA dosage (0.25 mg/kg/d) and monoclonal antibodies directed against the interleukin-2 receptor (IL-2R, CD25) and the intercellular adhesion molecule-1 (ICAM-1, CD54) was administered from postoperative d 0 to d 13. Cell migration and cell activation within liver grafts was assessed by standard histology and flow cytometry. IHL apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP-digoxigenin nick end labeling (TUNEL). RESULTS: Both CsA monotherapy and triple therapy prolonged liver allograft survival to more than 100 d and led to the induction of donor-specific tolerance. Untreated recipients rejected their allografts within 14 d. In both groups, donor-specific IHLs initially dropped to 18% to 25% on d 10, but they rebounded to as much as 40% on d 100 as a common characteristic of both groups. Within this population, donor-specific T cells were dominant. In both groups, increased numbers of activated (IL-2R+) CD8+ T lymphocytes were present on d 100. No accumulation of apoptotic IHL was observed on d 100. Their proportion was unchanged in the triple therapy group and slightly decreased in the CsA group compared to the syngeneic controls. CONCLUSIONS: The present study reveals that tolerant liver allografts are repopulated by donor-specific T lymphocytes. This phenomenon is independent of the type of applied immunosuppression. The persistence of activated CD8+ T cells in the phase of proven donor-specific tolerance on d 100 indicates that liver tolerance is associated with the state of a permanent intragraft immune activation. It seems that the coexistence of donor cells with infiltrating recipient cells within liver grafts, termed intrahepatic cell chimerism, is characteristic for tolerated liver allografts.

Animals↗

Orthotopic liver/small bowel transplantation in rats: a microsurgical model inducing tolerance.

Liver cirrhosis in patients with short bowel syndrome is successfully treated in humans by simultaneous liver/small bowel transplantation. However, until now, a clinically relevant experimental rat model for this procedure has not existed. We therefore established a protocol that, for the first time in rats, allows the simultaneous transplantation of arterialized liver and small bowel into an orthotopic position. Short-term immunosuppression induced not only allograft acceptance but tolerance (as demonstrated by indicator heart/skin transplantation). The immunosuppressive dose required to achieve this result was dramatically less than that of protocols for successful small bowel transplantation alone. Immunohistochemistry detected a transient rejection crisis before tolerance. During this crisis, apoptotic recipient-type T lymphocytes, mainly CD8+ cells, accumulated in the liver but not in the small bowel allograft. The initiation of T-cell apoptosis is one possible explanation for the specific immunosuppressive effect of the liver allograft, which also supports the simultaneously transplanted small bowel allograft in our model.

Animals↗

[Sweat gland carcinoma in the axillary area. A case report and review of the literature].

The sweat gland carcinoma is a rare tumor, representing in approximately 1% of primary skin lesions. In the literature 220 cases of sweat gland carcinomas have been presented over the last three decades. The medium age is 57 years, with an equal male-to-female distribution. Topographically, the tumor is located at the lower limbs (32.9%), the upper extremities (28%), and the head (26%). Involvement of the trunk is rare. Diagnosis can be complicated as the carcinoma is a rare entity, with no correlation of its histologic classification and biologic presentation. This can only implicate the difficulties in treatment.

Adenocarcinoma↗

Phase II study of weekly 24-hour intra-arterial high-dose infusion of 5-fluorouracil and folinic acid for liver metastases from colorectal carcinomas.

BACKGROUND: A multicenter phase II trial was initiated in order to evaluate the weekly, high-dose 24-hour infusion of 5-fluorouracil (5-FU) plus folinic acid (FA) in patients with unresectable colorectal cancer hepatic metastases. PATIENTS AND METHODS: A weekly hepatic arterial infusion (HAI) of FA 500 mg/m2 followed by a 24-hour infusion of 5-FU 2,600 mg/m2 (later reduced to 2,200 mg/m2) was given via a surgically implanted intra-arterial port system. One treatment cycle consisted of six weekly applications followed by a two-week rest period. Toxicity was assessed according to the WHO criteria. Chemotherapy was continued until disease progression or complete response occurred. RESULTS: A total of 50 patients (40 chemonaive, 10 pre-treated) entered this trial. An objective tumor response occurred in 28 patients (56%), while 13 patients (26%) had stable disease. The median progression free survival was 12 months, and the median survival 22.3 months. Due to a high rate of gastrointestinal side-effects in the initial phase of the trial, the dosage of 5-FU was reduced to 2,200 mg/m2 for all subsequent patients. Diarrhea and nausea led to a dose reduction in 40% of applications and 24% of patients, respectively. One patient died of cardiac insufficiency unrelated to chemotherapy before response evaluation. CONCLUSIONS: This HAI approach using high-dose 5-FU was relatively well tolerated when 2,200 mg/m2 instead of 2,600 mg/m2 was used. The activity of this regimen is promising and warrants further evaluation and modification.

Adenocarcinoma↗

Sclerosing cholangitis and liver cirrhosis after extrabiliary infections: report on three cases.

OBJECTIVE: To describe three unusual cases of sclerosing cholangitis after severe extrahepatic/extrabiliary bacterial infections. DESIGN: Case report, clinical. SETTING: Tertiary care intensive care unit (ICU). PATIENTS: Three patients admitted to the ICU with infections from Gram-positive bacteria followed by sclerosing cholangitis and secondary biliary cirrhosis. MAIN RESULTS: Three unusual cases of persisting cholestasis that occurred after bacterial infections originating from extrahepatic/extrabiliary foci are described. Endoscopic retrograde cholangiopancreatography and magnetic resonance cholangiopancreatography revealed multiple strictures of the intrahepatic bile ducts as a sign of sclerosing cholangitis. All patients progressed to biliary cirrhosis within months after the onset of cholestasis. CONCLUSION: Infection-associated cholestasis is usually a functional disorder and subsides after effective treatment of the underlying inflammatory focus. In rare cases, however, extrahepatic/extrabiliary infections may lead to sclerosing cholangitis and secondary biliary cirrhosis via unknown mechanisms.

Adult↗

Tolerance of rat liver allografts induced by short-term selective immunosuppression combining monoclonal antibodies directed against CD25 and CD54 with subtherapeutic cyclosporine.

BACKGROUND: Our purpose was to develop and evaluate protocols for selective immunosuppression after liver transplantation using the monoclonal antibodies (mAbs) NDS-61, directed against the interleukin-2 receptor (CD25), and 1A29, directed against the intercellular adhesion molecule-1 (CD54), in combination with subtherapeutic cyclosporine (CsA). METHODS: Orthotopic rat liver transplantation (ORLT) was performed in a DA-to-LEW strain combination. Immunosuppression was administered from day 0 to +13. Functional parameters such as survival time, body weight, and serum bilirubin levels were measured and the liver grafts were evaluated histologically. RESULTS: A stepwise tapering of CsA from 3 to 0.25 mg/kg/day reduced the long-term survival rate. All animals died at a CsA dosage of 0.25 mg/kg/day, which was therefore defined as subtherapeutic. Monotherapy with the anti-CD25 mAb was performed at dosages of 600 and 1800 microg/kg/day. The lower mAb dosage resulted in a long-term survival rate of 12% and was defined as subtherapeutic. The combination therapy of CsA (0.25 mg/kg/day) and anti-CD25 mAb (600 microg/kg/day) produced a synergistic effect and led to a long-term survival rate of 84%. This survival rate was significantly higher than those after either CsA (P<0.005) or anti-CD25 mAb (P<0.001) monotherapy. Both dosages (10 and 30 microg/kg/day) of anti-CD54 mAb monotherapy as well as anti-CD54 mAb combined with a subtherapeutic dosage of CsA were ineffective in preventing acute allograft rejection. The addition of anti-CD54 mAb (30 microg/kg/day) to combined CsA plus anti-CD25 mAb therapy (triple therapy), however, increased the long-term survival rate to 100%. In the triple therapy group there was no rejection process in the liver allografts at any time, and donor-specific tolerance could be shown by donor-specific and third-party heterotopic heart transplantation. CONCLUSIONS: The synergistic action of subtherapeutic CsA plus anti-CD25 mAb NDS-60 could be demonstrated, whereas anti-CD54 mAb only had a positive effect in a triple therapy group. Triple therapy prevented both acute and chronic rejection and induced donor-specific tolerance.

Animals↗

Donor-derived alloantigen-presenting cells persist in the liver allograft during tolerance induction.

The predictive value of chimerism was evaluated in three different transplantation models in the rat without immunosuppression: small bowel- (SBTx), liver- (LTx), and liver/small bowel transplantation (LSBTx) were performed in the Brown Norway (BN)-to-Lewis-(LEW) strain combination. Immunohistochemistry and flow cytometry were used to identify donor cells in the recipient's spleen. Their number did not change significantly during transient rejection or tolerance after LTx and LSBTx. However, the amount of donor-derived nonparenchymal cells within the liver allograft including antigen-presenting cells (APCs), such as dendritic and Kupffer cells, clearly mirrored the recipient's immune status: as expected, their number decreased during rejection, but recovered considerably during and after tolerance induction. We conclude that donor cells in the periphery of the recipient correlate with the presence of the allograft, but do not seem to influence graft acceptance actively. However, the kinetics of the detected donor APC population in the liver suggests their important role in modifying the recipient's immune response towards tolerance.

Animals↗

"Tolerogenic effect" of the liver for a small bowel allograft.

A newly developed liver/small bowel transplantation model (LSBTx) was used to investigate the tolerogenic effect of a liver allograft toward a simultaneously transplanted small bowel. Small bowel transplantation (SBTx) under high-dose immunosuppression was compared to LSBTx with a lower FK506 dosage. Syngeneic Lewis [(LEW) to LEW] and two fully allogeneic rat strain combinations (Brown Norway-to-LEW and Dark Agouti-to-LEW) were used. Clinical course and histological findings after SBTx demonstrated a chronic rejection of the small bowel allograft within 100 days. However, after LSBTx long-term acceptance (> 150 days) was achieved after a transient rejection crisis, although initial immunosuppression was significantly lower. Furthermore, indicator heart transplantations demonstrated the induction of donor-specific tolerance in both allogeneic strain combinations. In contrast to other LSBTx rat models, these results reflect observations after human LSBTx, in which the rate of acute and chronic rejection is also significantly lower than after human SBTx.

Acute Disease↗

Analysis of cellular events in hepatic allografts: donor progenitors induce intragraft chimerism.

Long-term graft acceptance and tolerance induction after allogeneic rat liver transplantation are well described. However, the underlying mechanisms remain unclear. In this study we investigated the cellular events within the liver graft during initial immunosuppression and long-term acceptance. Orthotopic liver transplantation was performed in the Dark Agouti (DA)-to-Lewis (LEW) and LEW-to-DA rat strain combination. In order to achieve long-term acceptance, LEW recipients of DA livers were treated with two different short-term therapies. Non-parenchymal cells (NPC) were isolated from liver allografts on days + 10 and + 100 after transplantation and donor-specific leukocytes were immunophenotyped by flow cytometry. Both the monotherapy and triple therapy prolonged graft survival (> 100 days). Liver allografts from LEW donors into DA recipients were spontaneously accepted across a complete MHC mismatch without immunosuppression. Liver allograft rejection was induced by infiltrating alloreactive immunocompetent cells. But the intensities of cell infiltration in the early and late phases after transplantation did not correlate with eventual outcome. Donor-specific NPC decreased to 18-25% on day + 10 in both therapeutic groups, but had rebounded to up to 40% by day + 100. Recurrence of donor-specific cells was caused almost exclusively by rising T cell counts. The persistence of dendritic cells in the late phase after transplantation could be clearly demonstrated. Repopulation by donor-specific T lymphocytes was observed in long-term accepted liver grafts. This recurrence may be based on the differentiation of liver-derived progenitor cells. The persistent coexistence of donor and recipient cells within the liver allograft (intrahepatic chimerism) appears to be characteristic and may be important for long-term acceptance.

Animals↗