[Surgical therapy of proximal extrahepatic bile duct tumors (Klatskin tumors)]. / Die chirurgische Therapie proximaler extrahepatischer Gallengangstumoren (Klatskin-Tumoren).

Due to their anatomical position, the tendency of early infiltrative growth and their poor prognosis without treatment, klatskin tumors are challenging concerning diagnosis and therapy. In contrast to other tumors of the gastrointestinal tract, for which exact diagnostic and stage dependent therapeutic guidelines could be formulated, clear recommendations for klatskin tumors are missing. Thus, survival rates after local resection, e. g. resection of the bile duct bifurcation alone, show high rates of R1/2 resection and early tumor recurrence. With an additional hepatic resection formally curative resections and long-term survival can be improved. Extended liver resections including the portal vein provide the highest rates of R0 resections for hilar carcinomas of the extrahepatic bile duct. Survival rates after liver transplantation for klatskin tumors are not yet convincing. Promising first results have been reported for the combination of neoadjuvant treatment and liver transplantation and might show future perspectives for the treatment of klatskin tumors.

Cytotoxic T-cell response following mouse liver transplantation is independent of the initial site of T-cell priming.

BACKGROUND: Liver transplantation in the mouse results in systemic induction of tolerance. The underlying mechanisms may also account for the persistence of chronic liver infections. It has therefore been hypothesized that antigen (Ag) presentation within the liver by nonprofessional antigen-presenting cells (APC) leads to incomplete T-cell activation, ultimately resulting in tolerance induction. We tested this hypothesis in an orthotopic mouse liver transplantation model. METHODS: Mouse liver transplantation was used to manipulate antigen presentation in major histocompatibility complex (MHC)-disparate donor and recipient strains. The effect of restricted Ag presentation was studied using CD8+ T-cell receptor transgenic OT-I cells. Transgenic OT-I cells were activated by injection of their cognate peptide antigen SIINFEKL, which could be presented by the MHC class I of only one of the mouse strains. Depending on the strain combination, Ag presentation was restricted to either the transplanted liver itself, the recipient (excluding the transplanted liver), or systemically throughout the recipient. Extrahepatic Ag presentation by passenger leukocytes was eliminated by using donors of chimeric bone marrow. RESULTS: OT-I cells encountering antigen only in the transplanted liver were activated, underwent extensive proliferation, and developed effector functions, based on IFN-gamma production and in vivo cytotoxicity assays. This T-cell activation and differentiation within the liver was comparable to animals with systemic Ag presentation and to animals with absent hepatic-parenchymal Ag presentation. CONCLUSIONS: The restricted presentation of antigen in the liver showed no immunosuppressive effect on activation of CD8+ T cells. In contrast, the liver may be an excellent priming site for naive CD8+ T cells.

Nematode infection of the liver mimicking metastasis of malignant melanoma.

BACKGROUND: The differential diagnoses of a circumscribed mass of the liver are varied. Especially if a malignant tumor, capable of setting metastases to the liver, is known in a patient's medical history, there might be difficulties in differentiating the tumor's entity. CASUISTRY: We report a case of a 40-year-old male with a history of malignant melanoma in whom follow-up investigations revealed a mass in the liver. RESULTS: The histopathological and microbiological results, however, showed an infestation of liver tissue with nematodes. Malignant tumor cells could not be detected. CONCLUSIONS: Roundworm-infections of the liver can present as lesions suspicious of being malignant. Therefore, along with e.g. microhamartoma, microabscesses and hepatocellular carcinoma, infestation with nematodes should be taken into consideration.

Retroperitoneal gas gangrene after colonoscopic polypectomy without bowel perforation in an otherwise healthy individual: report of a case.

BACKGROUND: Abdominal gas gangrene caused by clostridia species is rare and usually associated with organ perforation, immune suppression, or advanced malignoma. CASE REPORT: A 61-year-old man was admitted with severe back pain 1 day after uncomplicated colonoscopic polypectomy. With the exception of preexisting minor depression, the patient had been previously in excellent health. The computed tomography scan showed retroperitoneal emphysema in the left psoas muscle. During exploratory laparotomy, a spreading retroperitoneal phlegmon with pneumoretroperitoneum and a secondary peritonitis were found. A macroscopic perforation of the gut, particularly at the polypectomy sites was excluded. After the operation, the patient evolved in a septic shock condition and had pulmonary failure. Before hyperbaric oxygen therapy could be employed, the patient died. The autopsy showed a massive gas gangrene of the retroperitoneum caused by Clostridium perfringens, but no macroscopic bowel perforation was detected. RESULTS: This is the first report of a case of gas gangrene after uncomplicated polypectomy without macroscopic perforation in an otherwise healthy individual. A microperforation due to mucosal defect after polypectomy was most likely the entry point for the bacteria. CONCLUSION: We conclude that clostridial myonecrosis should be considered in unclear abdominal infections, even if the patient's history is not typical as in the present case.

[Therapeutically options for primary and secondary hepatic malignancies]. / Aktuelle Therapieoptionen bei primären und sekundären Lebermalignomen.

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.

[Nononcologic abdominal surgery in the elderly]. / Nichtonkologische Viszeralchirurgie im Alter.

Due to rising life expectancy of the population, the proportion of elderly patients requiring surgery is rising as well. Present aspects of selected, typical, nononcologic diseases of elderly people are discussed. The key to success in their treatment is not to consider primarily the patient's calendrical age but to assess the individual profile of risk factors on the basis of comorbidities. The kind, extent, and timing of an operation has to be based on this assessment. For the treatment of acute diseases (e.g., complicated ulcera, cholecystitis, appendicitis, mesenteric ischemia, and diverticulitis), a rapid and efficacious diagnostic algorithm is essential that takes into account the reduced functional reserve of old people. Constructive interdisciplinary cooperation and minimally invasive techniques play dominant roles in both diagnosis and therapy. Given these prerequisites, there is no reason to withhold surgical intervention from elderly patients.

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.

Prospective pilot study of neoadjuvant chemotherapy with 5-fluorouracil, folinic acid and oxaliplatin in resectable liver metastases of colorectal cancer. Analysis of 42 neoadjuvant chemotherapies.

PURPOSE: Since there are currently no data available from a prospective trial, the primary objective of this prospective study was to investigate whether the rate of R0-liver resections without morbidity would be at least 50 % in patients with neoadjuvant chemotherapy for colorectal liver metastases. PATIENTS AND METHODS: 42 patients were treated with a biweekly FOLFOX regimen. Chemotherapy consisted of a 2-hour infusion of folinic acid (FOL) 500 mg/m2, followed by a 24-hour infusion of 5- fluorouracil (F) 2000 mg/m2 daily for two days. Oxaliplatin (OX) 85 mg/m 2 was given simultaneously with FOL. Treatment allocation was randomized with either 3 or 6 cycles for the final 30 patients. A liver resection was performed 2 to 5 weeks after the final infusion. RESULTS: An objective response was observed in 20 of 42 patients (response rate was 27 % higher after 6 cycles). Liver resection (R0) could be performed in 34 patients. Postoperative complications were reported in 14 patients (13 occurring within 30 days after resection) and severe complications in 5 cases (including two deaths after extended resection). Liver failure and persistent biliary fistula were the most frequently documented complications. There was no relevant difference in safety criteria between 3 and 6 applications. CONCLUSION: The use of neoadjuvant chemotherapy in resectable liver metastases induced significant remissions without increasing morbidity. The rate of severe complications and cases of no R0-resection in this study was 31 % and was with that significantly lower than 50 % (95 % CI 17.6 %-47.1 %). The risk to the patient is therefore acceptable when undergoing neoadjuvant treatment in a prospective intergroup trial.

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.

Primary glomangioma of the liver: imaging findings.

Glomus organs are small arteriovenous anastomoses that are chiefly responsible for thermoregulation of the distal portion of the extremities. Glomangiomas are benign tumors of these bodies. Glomangiomas occur preferentially in the fingers and toes, but some case reports have described primary glomangiomas in the respiratory or gastrointestinal tract and the genitals. To date, no glomangiomas of the liver have been observed. We report on a 61-year-old patient in whom routine ultrasound disclosed a subcapsular well-defined mass in the liver. On imaging studies, no correspondence to the usual liver tumors was found. Magnetic resonance-guided biopsy showed a primary glomangioma of the liver. Clinically, the patient had no appetite and lost weight over several months. Due to the patient's weight loss and potential malignant transformation, the tumor was excised. Histologic work-up confirmed the diagnosis of a glomangioma with no signs of malignancy.

[Primary glomangioma of the liver. A new differential benign liver tumor diagnosis]. / Primäres Glomangiom der Leber. Eine neue Differenzialdiagnose benigner Lebertumoren.

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.

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.

[Endovascular therapy in combination with conventional vascular surgery for the treatment of peripheral arterial obliterative disease]. / Endovaskuläre Kombinationstherapie von Beckenarterienstenosen - Management intra- und postoperativer Komplikationen -

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.

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.

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.

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.

[Sweat gland carcinoma in the axillary area. A case report and review of the literature]. / Schweissdrüsencarcinom im Axillabereich. Eine Falldarstellung unter besonderer Berücksichtigung der Literatur.

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.