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Biomedical subjects

H U Baer

Publications and source records attributed to H U Baer.

At least 19 recordsLinked to original sources

Hepatic artery embolisation with a novel radiopaque polymer causes extended liver necrosis in pigs due to occlusion of the concomitant portal vein.

BACKGROUND/AIM: In an attempt to overcome some of the problems encountered with the materials available for liver embolisation, we investigated a novel radiopaque polymer of the polyurethane family (Degra-Bloc). METHODS: Hepatic artery embolisation of one liver lobe using polyurethane was performed in 19 healthy pigs. Microcirculatory changes were assessed by laser Doppler flowmetry. Radiological and pathological examinations of the livers, hearts and lungs removed provided information about the extent and effect of the embolisation. RESULTS: None of the pigs died due to hepatic failure or toxicity of polyurethane. Microcirculation of embolised liver lobes significantly decreased from 106 (+/-15) perfusion units (PU) to 45 (+/-6) PU immediately after embolisation and further to 28 (+/-7) PU before euthanasia. At this time conventional and angiographic X-ray controls demonstrated the radiopaque casts extending up to the peripheral arteries with signs of degradation over time but without formation of collateral vessels. The main pathological findings consisted of destruction of the portal tract structures and also of large areas of liver necrosis. Polyurethane was encountered in arterioles as small as 10-20 microm, but not in liver sinusoids, hearts or lungs. CONCLUSIONS: The novel polymer called DegraBloc is a biocompatible, slowly degradable, radiopaque embolic agent. The occlusion of the arterial tree up to the smallest arteriolar diameter combined with concomitant portal vein occlusion leads to sharp segmental necrosis in pig livers without formation of significant collaterals and without systemic embolism. In the treatment of liver tumours polyurethane might provide a promising alternative to conventional embolic materials, provided that it is used with care in patients with advanced liver cirrhosis.

Animals

Conservative surgical treatment of diffuse peritonitis.

BACKGROUND: Peritonitis is, even today, a significant source of death and complications. The objective of this study was to determine the morbidity and mortality rates, the incidence of reoperations, and the need for additional treatment strategies (on demand) in patients with diffuse peritonitis. METHODS: Prospective analysis including all patients (n = 258) with diffuse peritonitis admitted to our surgical service between November 1993 and April 1998 who underwent a uniform surgical treatment concept of peritonitis including early intervention, source control, and extensive intraoperative lavage. RESULTS: The 258 patients with diffuse peritonitis averaged a mean Mannheim Peritonitis Index of 27.1 points (range, 11-43 points). Source control at the initial operation was possible in 230 of the patients (89%), of those, 21 patients (9%) needed reintervention. In 28 patients (11%), source control was not possible at the initial operation. Twenty of these patients (71%) had to undergo additional treatment strategies (on demand) such as continuous lavage and/or laparostomy. Overall 228 of the 258 patients (88%) needed just 1 initial surgical intervention. The overall morbidity rate was 41%; the rate of reoperation was 12%, and the hospital mortality rate was 14%. CONCLUSIONS: A conservative surgical treatment concept supplemented with "extensive" intraoperative lavage reduces the reoperation rate compared with other treatment standards of peritonitis and achieves a low mortality rate in patients with diffuse peritonitis.

Adolescent

[The role of intravenous cholangiography in the era of laparoscopic cholecystectomy: is there a renaissance?].

BACKGROUND AND OBJECTIVE: The preoperative investigation for choledocholithiasis in patients undergoing elective laparoscopic cholecystectomy is still a matter of debate. PATIENTS AND METHODS: In a prospective clinical trial the accuracy of intravenous cholangiography (IVC), ultrasonography and liver function tests in the preoperative diagnosis of choledocholithiasis was assessed in 98 patients undergoing elective cholecystectomy. Only patients with uncomplicated cholecystolithiasis considered to be at low risk for having bile duct stones were investigated. A 2-year follow-up clinical survey (mean) was performed in 92 of the 98 patients to investigate the occurrence of postoperative choledocholithiasis (gold standard: clinically manifest choledocholithiasis). RESULTS: In this patient cohort the incidence of choledocholithiasis was found to be 5.1%. Among the three diagnostic tests IVC proved to be more accurate with higher sensitivity and a better positive predictive value than ultrasonography and liver function tests. The sensitivity for IVC was 100% compared to 20% for ultrasonography and 40% for liver function tests, respectively. The positive predictive value for IVC was 83.3% in comparison to 20% for ultrasonography and 25% for liver function tests. Mild side effects caused by intravenous contrast media were observed in 2.0%. During a mean postoperative follow-up of 2 years no clinically manifest and initially overlooked choledocholithiasis could be detected in the 92 investigated patients. CONCLUSION: IVC is a reliable method to detect unsuspected common bile duct stones and should be used in the preoperative diagnosis prior to elective laparoscopic cholecystectomy. IVC may play a role in decreasing the rate of preoperative ERCP or intraoperative cholangiography in these patients.

Adolescent

Small bowel tumors: diagnosis, therapy and prognostic factors.

BACKGROUND: Tumors of the small bowel are rare, accounting for about 3-6% of all gastrointestinal neoplasms. However, diagnosis and treatment are difficult and an ongoing challenge. METHODS: We retrospectively reviewed the medical records of 54 patients with tumors of the small intestine over a period of 10 years to elucidate important factors for diagnosis, therapy and prognosis. RESULTS: 42 patients had malignant (36 primary, 6 secondary) and 12 had benign tumors. Histologically, adenocarcinoma (33%), leiomyosarcoma (17%) and carcinoid (17%) were the most frequent malignancies found. All 12 benign lesions were either leiomyomas or adenomas. Initial symptoms were nonspecific: abdominal pain in 67% and 50%, anemia in 38% and 58% and weight loss in 38% and 42% in patients with malignant and benign tumors, respectively. Upper gastrointestinal series, endoscopy, computed tomography scan and selective angiography were the most useful diagnostic tools. Resectability rate for malignant tumors was 98%; curative resection was achieved in 51%. Survival for malignant tumors has been poor: median postoperative survival was 26.9 months, the 1- and 5-year survival rates were 42.9% and 20.8%, respectively. CONCLUSIONS: These results document the need for an aggressive diagnostic work-up in these rare tumors with non-specific symptoms, as early diagnosis and radical operative therapy are important prognostic factors.

Abdominal Pain

Transforming growth factor betas and their signaling receptors in human hepatocellular carcinoma.

BACKGROUND: Transforming growth factor betas (TGF-betas) are multifunctional polypeptides that have been suggested to influence tumor growth. They mediate their functions via specific cell surface receptors (type I ALK5 and type II TGF-beta receptors). The aim of this study was to analyze the roles of the three TGF-betas and their signaling receptors in human hepatocellular carcinoma (HCC). METHODS: HCC tissue samples were obtained from 18 patients undergoing partial liver resection. Normal liver tissues from 7 females and 3 males served as controls. The tissues for histological analysis were fixed in Bouin's solution and paraffin embedded. For RNA analysis, freshly obtained tissue samples were snap frozen in liquid nitrogen and stored at -80 degrees C until used. Northern blot analysis was used in normal liver and HCC to examine the expression of TGF-beta1, -beta2, -beta3 and their receptors: type I ALK5 (TbetaR-I ALK5), type II (TbetaR-II), and type III (TbetaR-III). Immunohistochemistry was performed to localize the corresponding proteins. RESULTS: All three TGF-betas demonstrated a marked mRNA overexpression in HCC in comparison with normal controls, whereas the levels of all three TGF-beta receptors showed no significant changes. Intense TGF-beta1, TGF-beta2, and TGF-beta3 immunostaining was found in hepatocellular carcinoma cells and in the perineoplastic stroma with immunohistochemistry, whereas no or mild immunostaining was present in the normal liver. For TbetaR-I ALK5 and TbetaR-II, the immunostaining in both HCC and normal liver was mild to moderate, with a slightly higher intensity in the normal tissues. CONCLUSION: The upregulation of TGF-betas in HCC suggests an important role for these isoforms in hepatic carcinogenesis and tumor progression. Moreover, the localization of the immunoreactivity in both malignant hepatocytes and stromal cells suggests that TGF-betas act via autocrine and paracrine pathways in this neoplasm.

Activin Receptors, Type I

Periampullary carcinomas: a special entity of duodenal tumors.

DEFINITION: Periampullary carcinomas are rare and constitute a special entity, as diagnosed earlier and having a better prognosis than other duodenal tumors. METHODS: In the present study, we retrospectively reviewed the medical records of 16 patients with periampullary carcinomas over 10 years. RESULTS: 16 patients, 10 men and 6 women (median age 66.7 years, range 42-80) had a malignant periampullary tumor. Initial symptoms were jaundice (88%), weight loss (69%), nausea and vomiting (50%) and abdominal pain (38%). Gastro-duodenoscopy, ERCP, ultrasound and CT scan were the most useful diagnostic tools. Histologically all the tumors were adenocarcinomas and solitary tumors. 91% were stage pT1 or pT2 tumors, localized in the duodenal wall without any infiltration of the pancreas. 36% of the tumors had metastasized either in lymph nodes or distant organs at diagnosis (18% pN1, 18% pM1). Resectability rate was 81%, curative resection was achieved in 62%. The operations performed were pancreatico-duodenectomy (n = 8), local tumor resection (n = 5) and palliative bypass (n = 3). Morbidity and reoperation rate were 37.5% and 18.8%, respectively; 30-day mortality was 0%. The 1- and 5-year survival rates were 58.3% and 33.3%, respectively. CONCLUSIONS: Compared to carcinomas of the small bowel or the exocrine pancreas periampullary carcinomas have a far better 5-year survival rate of more than 30%. Aggressive diagnostic workup in case of the leading symptom jaundice and radical operative therapy are key factors to achieve this goal.

Adult

Molecular aspects of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a highly malignant tumor with a poor prognosis. The success of its established treatment modalities is frequently limited by the advanced stage of the tumor at the time of diagnosis. Therefore, it is important to understand the mechanisms that control its growth behavior. In the present study, we review some aspects of molecular and cellular processes involved in growth control and metastatic potential of HCC. These include some growth factors and their receptors, oncogenes and tumor suppressor genes, and factors that control angiogenesis and extracellular matrix formation. These factors may be important targets for novel therapeutic approaches in the future.

Animals

[Surgical treatment of giant hemangiomas of the liver].

Giant liver hemangiomas are defined as hemangiomas with a diameter of more than 4 cm. They often require surgery due to bleeding tendencies or local compression. Between 1994 and 1998 we operated 11 patients with giant hemangiomas (median diameter 5.8 cm, range 4-12.5 cm). Average age was 50 years (range 23-85 years). 6 patients complained of pain, 1 patient sustained a bleeding. 7 hemangiomas were enucleated, 2 segmentally resected, 1 patient underwent a hemihepatectomy. 1 patient suffered from a bile leakage. Mortality was 0%. We conclude that clinically symptomatic liver hemangiomas can be safely resected. In a right sided localisation a enucleation has the best parenchyma sparing effect, in left sided locations a segmentectomy or bisegmentectomy can be performed with little blood loss.

Adult

[Solitary liver cysts and polycystic liver disease: aspects of surgical management of congenital cystic liver disease].

Congenital cystic liver disease represents a rare entity and only in 5%-20% the cysts cause symptoms or complications that demand therapy. In the past decades several therapeutic approaches have been developed with variable long-term outcome. We report herein our results and the postoperative outcome of 26 patients treated from 1987 to 1998 in our department because of symptomatic or complicated congenital cystic liver disease. In cases of symptom-producing solitary liver cysts our therapy of choice was laparoscopic fenestration. In cases of adult polycystic liver disease we mostly performed partial hepatic resection and fenestration. Both therapeutic approaches have proven a favorable long-term outcome. However, some types of adult polycystic liver disease possess a high risk of reappearance. Preoperative pathomorphological assessment of polycystic liver disease should be performed to choose the operative procedure in relation to the expected recurrence rate. Because of the progresses made in dialysis therapy and transplantation surgery in patients with adult polycystic kidney disease, an increase of patients with symptomatic polycystic liver disease has to be expected in the near future.

Adult

Intrapancreatic accessory spleen. A rare cause of a pancreatic mass.

CONCLUSION: The clinical significance of intrapancreatic accessory spleens resides in the mimicry of pancreatic cancer. Radionuclide tests (Octreotide scan and Tc99m sulfur colloid scan) should be undertaken to distinguish these lesions from neuroendocrine tumors, hypervascular metastases and pancreatic carcinoma. If the tests are equivocal, diagnostic laparotomy or laparoscopy is recommended. BACKGROUND: Despite its relatively common occurrence, intrapancreatic ectopic splenic tissue is rarely detected owing to its asymptomatic nature. METHODS: We report a case of a clinically asymptomatic patient in which abdominal computed tomography (CT) scans revealed a mass of 1.5 cm in diameter in the distal pancreas. The tumor markers CA 19-9 and carcinoembryonic antigen (CEA) were slightly elevated, and pancreatic neoplasm was suspected. RESULTS: Left pancreatic resection and splenectomy were performed. The removed specimen disclosed the presence of an accessory spleen within the pancreatic tail.

Aged

Acute hemorrhage in chronic pancreatitis: diagnosis and treatment options including superselective microcoil embolization.

Acute hemorrhage in the course of chronic pancreatitis is the most serious and challenging complication, and its treatment has been the subject of controversy for years. We relate our experience in the management of this complication by superselective microcoil embolization. Five patients with acute hemorrhage resulting from chronic pancreatitis between 1994 and 1997 were included in this study. All patients were men with a median age of 44 years (range, 29-59 years). The bleeding occurred into a pseudocyst in all patients, with the splenic artery as feeding vessel. In all instances, the bleeding was successfully controlled by superselective microcoil embolization. Two patients underwent subsequent uneventful elective pseudocystojejunostomy. There was no mortality or morbidity, and no rebleeding occurred during a median follow-up of 22 months (range, 8-36 months). In appropriate patients, diagnostic angiography and superselective microcoil embolization may obviate the need for emergency surgery and should be considered as treatment alternative.

Acute Disease

[New approaches to the surgical treatment of diffuse peritonitis].

OBJECTIVE: We intend to analyze if additional treatment concepts are necessary in any case as a part of the standard therapy next to the well established principle of source control in the treatment of secondary peritonitis. DESIGN: A treatment concept with early intervention, source control and extensive intraoperative lavage (20-301) should be evaluated as a standard procedure in a prospective survey. Additional treatment concepts will be applied only for special reason (on demand). RESULTS: From 11/1993 to 9/1997 241 patients with diffuse peritonitis were treated with the concept mentioned above. Additional treatment concepts as continuous postoperative lavage (n = 20) and staged lavage (n = 4) were applied as primary treatment in 24 patients only (10%), mainly for impossibility of source control and evisceration. Source control at the initial operation was possible in 216 patients (90%). Due to secondary evisceration 3 patients had to undergo laparostomy for staged lavage later. Severity of peritonitis was determined according to the Mannheim Peritonitis Index (median 26, range 15-43). The primary causes of peritonitis were perforation, leakage and abscess after operation (n = 56), followed by diverticular (n = 42) and gastric or duodenal perforation (n = 39). The hospital mortality rate was 14% in the whole group, and the postoperative morbidity rate was 39%. CONCLUSIONS: Due to progress in intensive care and antibiotic treatment only a few patients (ca. 10%) need additional therapies such as postoperative or staged lavage. Surgical source control in combination with intraoperative lavage is sufficient in most of the patients with diffuse peritonitis.

Adolescent

KAI1, a new metastasis suppressor gene, is reduced in metastatic hepatocellular carcinoma.

Down-regulation of KAI1 expression has been shown to be associated with formation of metastases or disease progression in prostate and pancreatic cancer. In the present study we analyzed the expression pattern of KAI1 in metastatic and nonmetastatic hepatocellular carcinomas (HCCs) in comparison with normal livers to evaluate whether alteration of KAI1 also facilitates the metastatic ability in this malignancy. Thirty-nine primary HCCs and 10 normal liver tissue samples were studied for KAI1 messenger RNA (mRNA) expression with use of Northern blot analysis and in situ hybridization. By Northern blot analysis, moderate to strong KAI1 mRNA expression was present in normal liver samples. In contrast, KAI1 mRNA expression in tissue samples of primary HCCs was markedly decreased compared with normal controls. The normal/tumor ratio of KAI1 mRNA expression was 2.6:1 (P <.01). Primary HCCs that gave rise to metastasis showed significantly lower KAI1 mRNA levels than nonmetastasized HCCs (P <. 05). As seen by in situ hybridization, moderate to strong cytoplasmic KAI1 mRNA staining was present in almost all normal hepatocytes. Bile ducts, blood vessels, and connective tissue showed no or only faint KAI1 mRNA expression in the normal liver samples. In nonmetastatic HCCs, the cancer cells exhibited in situ hybridization signals that were similar to the normal controls. In contrast, most of the primary HCC cells in samples with metastases showed only faint or moderate KAI1 mRNA expression predominantly in the perinuclear regions. When KAI1 mRNA expression of primary hepatocellular cancer cells was compared with metastasized cancer cells in lymph nodes, with intrahepatic satellite metastasis, or with peritoneal metastasis in the same patients, significantly lower (P <.01) KAI1 mRNA levels were present in the metastasized HCC cells. Reduced KAI1 mRNA in HCC cells seems to influence their metastatic ability and thereby enhances the malignant potential of HCC.

Aged

Evaluation of laser Doppler flowmetry to assess cyclosporine A-induced impairment of renal blood flow.

Cyclosporine A (CyA)-induced nephrotoxicity is a well-known complication of this potent immunosuppressive drug. It is caused by an elevation in renovascular resistance and impairment of renal blood flow. Currently, one of the principal experimental settings to assess renal hemodynamics has been using the in vivo fluorescent videomicroscopy (IVFV) method on hydronephrotic rat kidneys, which is expensive, time-consuming, not physiological, and not applicable to humans. In the present paper we have been able to confirm our working hypothesis that laser Doppler flowmetry (LDF) is a valuable tool for assessing microcirculatory changes in the rat kidney during CyA administration. Total subcapsular blood flow decreased to approximately 70% of baseline values (P < 0.05) and mean arterial pressure (MAP) increased initially to 113% of baseline values (P < 0.05) compared to only minor changes for cremophor (carrier substance) or no changes for sodium chloride solution 0.9%. LDF provides an easy and rapid technique and its major advantage is the potential use in assessing microcirculatory changes after kidney transplants in humans.

Animals

Increased expression of erbB3 in colorectal cancer is associated with concomitant increase in the level of erbB2.

ErbB3 is a transmembrane signaling molecule that shares close structural homology with epidermal growth factor receptor (EGFR), erbB2, and erbB4. They have all been implicated in cell transformation and tumor pathogenesis, but very little is known about the role of erbB3 in normal colon and colorectal cancer. Therefore, in the current study, we determined whether erbB3 is found in normal human colon and whether its expression is altered in colorectal cancer. Because of some evidence that erbB3 might interact with erbB2 and EGFR, respectively, by heterodimerization, we also included erbB2 and EGFR analysis with special regard to coexpression. The study was performed on 35 patients operated on for colorectal carcinoma. The normal human colon showed weak erbB3 and erbB2 immunostaining, predominantly in surface epithelial cells. EGFR immunoreactivity in normal colon varied from weak to strong. In contrast, in 31 of 35 (89%) and in 29 of 35 (83%) colonic cancers, moderate to strong immunoreactivity for erbB3 and erbB2, respectively, was present in most epithelial cancer cells. A concomitant erbB3 and erbB2 immunostaining advantage could be found in 77% of cancerous tissues in comparison with the normal colon. No difference in EGFR immunostaining was evident between normal colon and cancer. Northern blot analysis showed an increase in erbB3 and erbB2 mRNA levels in 64% of cancers in comparison with normal colon samples. By densitometry, 2.3-fold and a 1.5-fold significant increases in erbB3 and erbB2 mRNA levels, respectively, were calculated in the cancerous tissues. Eighty-five percent of cancers with erbB3 mRNA overexpression showed an increase in erbB2 mRNA. Southern blot analysis did not indicate any gene amplification or rearrangement responsible for erbB2 or erbB3 overexpression. EGFR, however, was decreased in cancer on mRNA level. These findings indicate that erbB2 and erbB3, but not EGFR, may contribute to tumor growth and disease progression in colon cancer. The correlation between increased erbB2 and erbB3 expression in both Northern blots and immunohistochemical analysis suggests a co-overexpression of erbB2 and erbB3 and might support the hypothesis that these two growth factor receptors act together by heterodimer formation.

Adenocarcinoma

Biliary cystadenocarcinoma of the liver: the need for complete resection.

We report on a patient with biliary cystadenocarcinoma and review 112 previously published cases of this rare cystic hepatic neoplasm. This tumour mainly occurs in women at a ratio of 62% (female) to 38% (male), and at an average age of 56.2 years (range 18-88 years). The origin of these neoplasms is intrahepatic in 97% of cases and extrahepatic in the remaining 3%. The clinical symptoms are nonspecific and are not distinctive from benign cystic liver lesions unless invasive growth of the tumour occurs or distant metastases are present. Sonography and computed tomography (CT), as well as magnetic resonance imaging (MRI) demonstrate the multilocular nature of the tumour with septal or mural nodules. Discrete soft tissue masses, thick and coarse calcifications and varying density on CT or intensity on MRI within the loculi are additional non-specific imaging findings. The best therapeutic result with a 5-year survival rate of 100% and a recurrence rate of only 13% was achieved by complete excision (n = 16). Surgical removal of the tumour by complete excision is, therefore, the treatment of choice for biliary cystadenocarcinomas.

Aged